14309 lines
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Entry
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- *150330 - LAMIN A/C; LMNA
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*150330</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/150330">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000160789;t=ENST00000368300" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4000" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=150330" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000160789;t=ENST00000368300" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001257374,NM_001282624,NM_001282625,NM_001282626,NM_001406983,NM_001406984,NM_001406985,NM_001406986,NM_001406987,NM_001406988,NM_001406989,NM_001406990,NM_001406991,NM_001406992,NM_001406993,NM_001406994,NM_001406995,NM_001406996,NM_001406997,NM_001406998,NM_001406999,NM_001407000,NM_001407001,NM_001407002,NM_001407003,NM_005572,NM_170707,NM_170708" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_170707" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=150330" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=01035&isoform_id=01035_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/LMNA" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/34228,34236,125962,307108,386856,5031875,12653479,13111979,14290259,21619981,27436946,27436948,39653934,54035059,57014043,57014045,57014047,77819840,119573381,119573382,119573383,119573384,119573385,194376756,194379984,308219524,308219718,308219722,383792150,544063464,544063466,544063468,578003955,578003957,578003959,578003961,578003963,578003965,578003967,578003969,578003971,578003973,578003975,578003977,578003979,578003981,593023778,2243207293,2243207636,2244985380,2244985384,2244985394,2244985420,2244985445,2244985458,2244985505,2244985555,2244985630,2244986459,2244986463,2244986484,2244986507,2244986541,2244986551,2244986560,2244986590,2244986610,2244986618,2300970617" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P02545" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=4000" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000160789;t=ENST00000368300" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=LMNA" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=LMNA" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+4000" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/LMNA" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:4000" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/4000" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000368300.9&hgg_start=156082573&hgg_end=156140081&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:6636" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6636" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=150330[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=150330[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/LMNA/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000160789" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=LMNA" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=LMNA" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LMNA" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/LMNA" title="Leiden Muscular Dystrophy Pages" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Leiden Muscular Dystrophy …</a></div><div style="margin-left: 0.5em;"><a href="http://www.molgen.ua.ac.be/CMTMutations/" title="Inherited Peripheral Neuropathies Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Inherited Peripheral Neuro…</a></div><div style="margin-left: 0.5em;"><a href="http://www.umd.be/LMNA/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The LMNA mutations database</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=LMNA&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA231" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:6636" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0002525.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96794" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/LMNA#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:96794" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/4000/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001213,002796" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4000" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00003052;class=Gene" 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'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-020424-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:150330" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4000" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=LMNA&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1003431005, 1010712009, 238870004, 53043001, 715439000, 719451006, 721014007, 725048002, 771272007<br />
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<strong>ICD10CM:</strong> E34.8<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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150330
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
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<span class="mim-font">
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LAMIN A/C; LMNA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
|
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<span class="h3 mim-font">
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LAMIN A, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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LAMIN C, INCLUDED; LMNC, INCLUDED<br />
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PRELAMIN A, INCLUDED<br />
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PROGERIN, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LMNA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LMNA</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1240?start=-3&limit=10&highlight=1240">1q22</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:156082573-156140081&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:156,082,573-156,140,081</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
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<a href="/clinicalSynopsis/table?mimNumber=115200,605588,181350,616516,610140,176670,151660,212112,248370,613205,619793" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="11">
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<span class="mim-font">
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<a href="/geneMap/1/1240?start=-3&limit=10&highlight=1240">
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1q22
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Cardiomyopathy, dilated, 1A
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/115200"> 115200 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, type 2B1
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
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|
<a href="/entry/605588"> 605588 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
|
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</tr>
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|
|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emery-Dreifuss muscular dystrophy 2, autosomal dominant
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|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/181350"> 181350 </a>
|
|
|
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</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>
|
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|
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</span>
|
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</td>
|
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</tr>
|
|
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|
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emery-Dreifuss muscular dystrophy 3, autosomal recessive
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616516"> 616516 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Heart-hand syndrome, Slovenian type
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|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/610140"> 610140 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Lipodystrophy, familial partial, type 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/151660"> 151660 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Malouf syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/212112"> 212112 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mandibuloacral dysplasia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/248370"> 248370 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, congenital
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613205"> 613205 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Restrictive dermopathy 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619793"> 619793 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
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<div>
|
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|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/150330" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/150330" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="text" class="mim-anchor"></a>
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|
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|
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<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
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|
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<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The LMNA gene encodes lamin A and lamin C. Lamins are structural protein components of the nuclear lamina, a protein network underlying the inner nuclear membrane that determines nuclear shape and size. The lamins constitute a class of intermediate filaments. Three types of lamins, A, B (see LMNB1; <a href="/entry/150340">150340</a>), and C, have been described in mammalian cells (<a href="#33" class="mim-tip-reference" title="Fisher, D. Z., Chaudhary, N., Blobel, G. <strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong> Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3462705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3462705</a>] [<a href="https://doi.org/10.1073/pnas.83.17.6450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3462705">Fisher et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3462705" 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>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
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<span class="mim-text-font">
|
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<p>By screening human fibroblast and hepatoma cDNA libraries, <a href="#33" class="mim-tip-reference" title="Fisher, D. Z., Chaudhary, N., Blobel, G. <strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong> Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3462705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3462705</a>] [<a href="https://doi.org/10.1073/pnas.83.17.6450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3462705">Fisher et al. (1986)</a> isolated cDNAs corresponding to lamin A and lamin C. The lamin A and C proteins are predicted to have molecular masses of 74 kD and 65 kD, respectively. <a href="#33" class="mim-tip-reference" title="Fisher, D. Z., Chaudhary, N., Blobel, G. <strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong> Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3462705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3462705</a>] [<a href="https://doi.org/10.1073/pnas.83.17.6450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3462705">Fisher et al. (1986)</a> and <a href="#77" class="mim-tip-reference" title="McKeon, F. D., Kirschner, M. W., Caput, D. <strong>Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.</strong> Nature 319: 463-468, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3453101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3453101</a>] [<a href="https://doi.org/10.1038/319463a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3453101">McKeon et al. (1986)</a> found that the deduced amino acid sequences from cDNA clones of human lamin A and C are identical for the first 566 amino acids, but that lamin A contains an extra 98 amino acids (corresponding to approximately 9 kD) at the C terminus. Lamin C has 6 unique C-terminal amino acids. Both lamins A and C contain a 360-residue alpha-helical domain with homology to a corresponding alpha-helical rod domain that is the structural hallmark of all intermediate filament proteins. <a href="#33" class="mim-tip-reference" title="Fisher, D. Z., Chaudhary, N., Blobel, G. <strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong> Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3462705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3462705</a>] [<a href="https://doi.org/10.1073/pnas.83.17.6450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3462705">Fisher et al. (1986)</a> and <a href="#77" class="mim-tip-reference" title="McKeon, F. D., Kirschner, M. W., Caput, D. <strong>Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.</strong> Nature 319: 463-468, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3453101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3453101</a>] [<a href="https://doi.org/10.1038/319463a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3453101">McKeon et al. (1986)</a> concluded that lamin A and lamin C arise by alternative splicing from the same gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3462705+3453101" 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="Guilly, M. N., Bensussan, A., Bourge, J. F., Bornens, M., Courvalin, J. C. <strong>A human T lymphoblastic cell line lacks lamins A and C.</strong> EMBO J. 6: 3795-3799, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3501373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3501373</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02715.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3501373">Guilly et al. (1987)</a> detected a 3-kb lamin A mRNA and a 2.1-kb lamin C mRNA in epithelial HeLa cells, but not in T lymphoblasts. Lamin B was the only lamin present in T lymphoblasts. <a href="#45" class="mim-tip-reference" title="Guilly, M. N., Bensussan, A., Bourge, J. F., Bornens, M., Courvalin, J. C. <strong>A human T lymphoblastic cell line lacks lamins A and C.</strong> EMBO J. 6: 3795-3799, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3501373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3501373</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02715.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3501373">Guilly et al. (1987)</a> noted that the transport of newly synthesized proteins from the cytoplasm into the nucleus differs from the transport of proteins into other organelles, such as mitochondria, in that sequences are not cleaved and remain a permanent feature of the mature polypeptide. Lamin A appears to be an exception to this rule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3501373" 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="#134" class="mim-tip-reference" title="Weber, K., Plessmann, U., Traub, P. <strong>Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina.</strong> FEBS Lett. 257: 411-414, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2583287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2583287</a>] [<a href="https://doi.org/10.1016/0014-5793(89)81584-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2583287">Weber et al. (1989)</a> showed that lamin A is synthesized as a precursor molecule called prelamin A. Maturation of lamin A involves the removal of 18 residues from the C terminus, which is accomplished by isoprenylation and farnesylation involving a C-terminal CAAX (cysteine-aliphatic-aliphatic-any amino acid) box (<a href="#115" class="mim-tip-reference" title="Sinensky, M., Fantle, K., Trujillo, M., McLain, T., Kupfer, A., Dalton, M. <strong>The processing pathway of prelamin A.</strong> J. Cell Sci. 107: 61-67, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8175923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8175923</a>] [<a href="https://doi.org/10.1242/jcs.107.1.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8175923">Sinensky et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2583287+8175923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR analysis of several human cell lines, <a href="#73" class="mim-tip-reference" title="Machiels, B. M., Zorenc, A. H. G., Endert, J. M., Kuijpers, H. J. H., van Eys, G. J. J. M., Ramaekers, F. C. S., Broers, J. L. V. <strong>An alternative splicing product of the lamin A/C gene lacks exon 10.</strong> J. Biol. Chem. 271: 9249-9253, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621584</a>] [<a href="https://doi.org/10.1074/jbc.271.16.9249" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8621584">Machiels et al. (1996)</a> identified an LMNA splice variant, lamin A-delta-10, that lacks exon 10. The predicted protein lacks 30 amino acids in the lamin A tail, which in full-length lamin A contains an aspartic acid- and glutamine-rich stretch, followed by 4 consecutive histidines. Variable lamin A-delta-10 expression was detected in all cell lines and tissues examined. The ratio of lamin A to lamin A-delta-10 varied among samples. Western blot analysis of a 2-dimensional gel revealed a lamin A doublet with an apparent molecular mass of approximately 70 kD and a second, more basic protein of approximately 65 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8621584" 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 Western blot analysis, <a href="#58" class="mim-tip-reference" title="Jung, H.-J., Coffinier, C., Choe, Y., Beigneux, A. P., Davies, B. S. J., Yang, S. H., Barnes, R. H., II, Hong, J., Sun, T., Pleasure, S. J., Young, S. G., Fong, L. G. <strong>Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA.</strong> Proc. Nat. Acad. Sci. 109: E423-E431, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22308344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22308344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22308344[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1111780109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22308344">Jung et al. (2012)</a> found that lamins A and C were highly expressed in mouse heart, liver, and kidney, with lamin A showing slightly higher expression than lamin C. In contrast, expression of lamin A was much lower than that of lamin C in cerebral cortex and cerebellum. Immunohistochemical analysis revealed that only vascular and meningeal cells in mouse brain expressed significant lamin A, whereas lamin C showed widespread expression in brain. Northern blot analysis and quantitative RT-PCR confirmed high expression of lamin C, but not lamin A, in mouse cerebral cortex and cerebellum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22308344" 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="#114" class="mim-tip-reference" title="Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L. <strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong> Molec. Biol. Cell 24: 342-350, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23243001">Simon et al. (2013)</a> stated that prelamin A is C-terminally farnesylated and carboxymethylated, then proteolytically cleaved after tyr646 (Y646) to generate mature lamin A. Mature lamin A can be further modified by acetylation, phosphorylation, or addition of N-acetylglucosamine, and the rod domain can be sumoylated by SUMO2 (<a href="/entry/603042">603042</a>). <a href="#114" class="mim-tip-reference" title="Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L. <strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong> Molec. Biol. Cell 24: 342-350, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23243001">Simon et al. (2013)</a> found that the tail domain of mature lamin A, comprising residues 385 to 646, was modified by SUMO1 (<a href="/entry/601912">601912</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23243001" 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="#69" class="mim-tip-reference" title="Lin, F., Worman, H. J. <strong>Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.</strong> J. Biol. Chem. 268: 16321-16326, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8344919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8344919</a>]" pmid="8344919">Lin and Worman (1993)</a> demonstrated that the coding region of the lamin A/C gene spans approximately 24 kb and contains 12 exons. Alternative splicing within exon 10 gives rise to 2 different mRNAs that code for prelamin A and lamin C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8344919" 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="#138" class="mim-tip-reference" title="Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B. <strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong> Genomics 32: 474-478, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838815</a>] [<a href="https://doi.org/10.1006/geno.1996.0146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8838815">Wydner et al. (1996)</a> mapped the LMNA gene to chromosome 1q21.2-q21.3 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838815" 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="#44" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 3/26/2013."None>Gross (2013)</a> mapped the LMNA gene to chromosome 1q22 based on an alignment of the LMNA sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AY847595" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AY847595</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#71" class="mim-tip-reference" title="Lloyd, D. J., Trembath, R. C., Shackleton, S. <strong>A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.</strong> Hum. Molec. Genet. 11: 769-777, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929849</a>] [<a href="https://doi.org/10.1093/hmg/11.7.769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11929849">Lloyd et al. (2002)</a> identified proteins interacting with the C-terminal domain of lamin A by screening a mouse 3T3-L1 adipocyte library in a yeast 2-hybrid interaction screen. Using this approach, the adipocyte differentiation factor SREBP1 (<a href="/entry/184756">184756</a>) was identified as a novel lamin A interactor. In vitro glutathione S-transferase pull-down and in vivo coimmunoprecipitation studies confirmed an interaction between lamin A and both SREBP1a and 1c. A binding site for lamin A was identified in the N-terminal transcription factor domain of SREBP1, between residues 227 and 487. The binding of lamin A to SREBP1 was noticeably reduced by FPLD mutations. The authors speculated that fat loss seen in laminopathies may be caused in part by reduced binding of the adipocyte differentiation factor SREBP1 to lamin A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11929849" 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="Favreau, C., Higuet, D., Courvalin, J.-C., Buendia, B. <strong>Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.</strong> Molec. Cell. Biol. 24: 1481-1492, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749366</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14749366[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.4.1481-1492.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14749366">Favreau et al. (2004)</a> analyzed myoblast-to-myotube differentiation in a mouse myogenic cell line overexpressing wildtype or mutant human lamin A. In contrast to clones overexpressing wildtype lamin A, those expressing lamin A with the R453W mutation (<a href="#0002">150330.0002</a>) differentiated poorly or not at all, did not exit the cell cycle properly, and were extensively committed to apoptosis. Clones expressing the R482W mutation (<a href="#0011">150330.0011</a>) differentiated normally. <a href="#32" class="mim-tip-reference" title="Favreau, C., Higuet, D., Courvalin, J.-C., Buendia, B. <strong>Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.</strong> Molec. Cell. Biol. 24: 1481-1492, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749366</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14749366[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.4.1481-1492.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14749366">Favreau et al. (2004)</a> concluded that lamin A mutated at arginine-453 fails to build a functional scaffold and/or fails to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14749366" 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 a novel technique to measure nuclear deformation in response to biaxial strain applied to cells, <a href="#65" class="mim-tip-reference" title="Lammerding, J., Schulze, P. C., Takahashi, T., Kozlov, S., Sullivan, T., Kamm, R. D., Stewart, C. L., Lee, R. T. <strong>Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.</strong> J. Clin. Invest. 113: 370-378, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14755334[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI19670" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755334">Lammerding et al. (2004)</a> found that Lmna -/- cells showed increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain compared to wildtype cells. In addition, activity of nuclear factor-kappa-B (NFKB; <a href="/entry/164011">164011</a>), a mechanical stress-responsive transcription factor that can act as an antiapoptotic signal, was impaired in the Lmna -/- cells. The findings suggested that lamin A/C deficiency is associated with both defective nuclear mechanics and impaired transcriptional activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14755334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Broers, J. L. V., Peeters, E. A. G., Kuijpers, H. J. H., Endert, J., Bouten, C. V. C., Oomens, C. W. J., Baaijens, F. P. T., Ramaekers, F. C. S. <strong>Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies.</strong> Hum. Molec. Genet. 13: 2567-2580, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367494</a>] [<a href="https://doi.org/10.1093/hmg/ddh295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367494">Broers et al. (2004)</a> used a cell compression device to compare wildtype and Lmna-knockout mouse embryonic fibroblasts, and found that Lmna-null cells showed significantly decreased mechanical stiffness and significantly lower bursting force. Partial rescue of the phenotype by transfection with either lamin A or lamin C prevented gross nuclear disruption, but was unable to fully restore mechanical stiffness. Confocal microscopy revealed that the nuclei of Lmna-null cells exhibited an isotropic deformation upon indentation, despite an anisotropic deformation of the cell as a whole. This nuclear behavior suggested a loss of interaction of the disturbed nucleus with the surrounding cytoskeleton. Actin (<a href="/entry/102610">102610</a>)-, vimentin (<a href="/entry/193060">193060</a>)-, and tubulin (<a href="/entry/191110">191110</a>)-based filaments showed disturbed interaction in Lmna-null cells. <a href="#8" class="mim-tip-reference" title="Broers, J. L. V., Peeters, E. A. G., Kuijpers, H. J. H., Endert, J., Bouten, C. V. C., Oomens, C. W. J., Baaijens, F. P. T., Ramaekers, F. C. S. <strong>Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies.</strong> Hum. Molec. Genet. 13: 2567-2580, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367494</a>] [<a href="https://doi.org/10.1093/hmg/ddh295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367494">Broers et al. (2004)</a> suggested that in addition to the loss of nuclear stiffness, the loss of a physical interaction between nuclear structures (i.e., lamins) and the cytoskeleton may cause more general cellular weakness; they proposed a potential key function for lamins in maintaining cellular tensegrity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367494" 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="#123" class="mim-tip-reference" title="Van Berlo, J. H., Voncken, J. W., Kubben, N., Broers, J. L. V., Duisters, R., van Leeuwen, R. E. W., Crijns, H. J. G. M., Ramaekers, F. C. S., Hutchison, C. J., Pinto, Y. M. <strong>A-type lamins are essential for TGF-beta-1 induced PP2A to dephosphorylate transcription factors.</strong> Hum. Molec. Genet. 14: 2839-2849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115815</a>] [<a href="https://doi.org/10.1093/hmg/ddi316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16115815">Van Berlo et al. (2005)</a> showed that A-type lamins were essential for the inhibition of fibroblast proliferation by TGF-beta-1 (<a href="/entry/190180">190180</a>). TGF-beta-1 dephosphorylated RB1 (<a href="/entry/614041">614041</a>) through protein phosphatase 2A (PPP2CA; <a href="/entry/176915">176915</a>), both of which were associated with lamin A/C. In addition, lamin A/C modulated the effect of TGF-beta-1 on collagen production, a marker of mesenchymal differentiation. <a href="#123" class="mim-tip-reference" title="Van Berlo, J. H., Voncken, J. W., Kubben, N., Broers, J. L. V., Duisters, R., van Leeuwen, R. E. W., Crijns, H. J. G. M., Ramaekers, F. C. S., Hutchison, C. J., Pinto, Y. M. <strong>A-type lamins are essential for TGF-beta-1 induced PP2A to dephosphorylate transcription factors.</strong> Hum. Molec. Genet. 14: 2839-2849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115815</a>] [<a href="https://doi.org/10.1093/hmg/ddi316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16115815">Van Berlo et al. (2005)</a> proposed a role for lamin A/C in control of gene activity downstream of TGF-beta-1, via nuclear phosphatases such as PPP2CA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Capanni, C., Mattioli, E., Columbaro, M., Lucarelli, E., Parnaik, V. K., Novelli, G., Wehnert, M., Cenni, V., Maraldi, N. M., Squarzoni, S., Lattanzi, G. <strong>Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.</strong> Hum. Molec. Genet. 14: 1489-1502, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843404</a>] [<a href="https://doi.org/10.1093/hmg/ddi158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843404">Capanni et al. (2005)</a> showed that the lamin A precursor was specifically accumulated in lipodystrophy cells. Pre-lamin A was located at the nuclear envelope and colocalized with SREBP1. Binding of SREBP1 to the lamin A precursor was detected in patient fibroblasts, as well as in control fibroblasts, forced to accumulate pre-lamin A by farnesylation inhibitors. In contrast, SREBP1 did not interact in vivo with mature lamin A or C in cultured fibroblasts. Inhibition of lamin A precursor processing in 3T3-L1 preadipocytes resulted in sequestration of SREBP1 at the nuclear rim, thus decreasing the pool of active SREBP1 that normally activates PPAR-gamma (<a href="/entry/601487">601487</a>) and causing impairment of preadipocyte differentiation. This defect could be rescued by treatment with troglitazone, a known PPAR-gamma ligand activating the adipogenic program. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843404" 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 yeast 2-hybrid analysis and protein pull-down assays, <a href="#68" class="mim-tip-reference" title="Libotte, T., Zaim, H., Abraham, S., Padmakumar, V. C., Schneider, M., Lu, W., Munck, M., Hutchison, C., Wehnert, M., Fahrenkrog, B., Sauder, U., Aebi, U., Noegel, A. A., Karakesisoglou, I. <strong>Lamin A/C-dependent localization of nesprin-2, a giant scaffolder at the nuclear envelope.</strong> Molec. Biol. Cell 16: 3411-3424, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843432</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15843432[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.e04-11-1009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843432">Libotte et al. (2005)</a> found that the last 4 spectrin repeats at the C terminus of nesprin-2 (SYNE2; <a href="/entry/608442">608442</a>), a nuclear membrane scaffold protein, bound directly to a C-terminal region common to both lamins A and C. Knockdown studies with human cell lines revealed that lamin A/C was required for nesprin-2 nuclear envelope localization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843432" 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="#104" class="mim-tip-reference" title="Scaffidi, P., Misteli, T. <strong>Lamin A-dependent nuclear defects in human aging.</strong> Science 312: 1059-1063, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16645051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16645051</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16645051[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1127168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16645051">Scaffidi and Misteli (2006)</a> showed that the same molecular mechanism responsible for Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>) is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. <a href="#104" class="mim-tip-reference" title="Scaffidi, P., Misteli, T. <strong>Lamin A-dependent nuclear defects in human aging.</strong> Science 312: 1059-1063, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16645051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16645051</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16645051[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1127168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16645051">Scaffidi and Misteli (2006)</a> concluded that their observations implicate lamin A in physiologic aging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16645051" 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>Human immunodeficiency virus (HIV)-1 (see <a href="/entry/609423">609423</a>) protease inhibitors (PIs) targeting the viral aspartyl protease are a cornerstone of treatment for HIV infection and disease, but they are associated with lipodystrophy and other side effects. <a href="#21" class="mim-tip-reference" title="Coffinier, C., Hudon, S. E., Farber, E. A., Chang, S. Y., Hrycyna, C. A., Young, S. G., Fong, L. G. <strong>HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.</strong> Proc. Nat. Acad. Sci. 104: 13432-13437, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17652517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17652517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17652517[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0704212104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17652517">Coffinier et al. (2007)</a> found that treatment of human and mouse fibroblasts with HIV-PIs caused an accumulation of prelamin A. The prelamin A in HIV-PI-treated fibroblasts migrated more rapidly than nonfarnesylated prelamin A, comigrating with the farnesylated form found in ZMPSTE24 (<a href="/entry/606480">606480</a>)-deficient fibroblasts. HIV-PI-treated heterozygous ZMPSTE24 fibroblasts exhibited an exaggerated accumulation of farnesyl-prelamin A. Western blot and enzymatic analysis showed that HIV-PIs inhibited ZMPSTE24 activity and endoproteolytic processing of a GFP-prelamin A fusion protein, but they did not affect farnesylation of HDJ2 (DNAJA1; <a href="/entry/602837">602837</a>) or activity of farnesyltransferase (see <a href="/entry/134635">134635</a>), ICMT (<a href="/entry/605851">605851</a>), and RCE1 (<a href="/entry/605385">605385</a>) in vitro. <a href="#21" class="mim-tip-reference" title="Coffinier, C., Hudon, S. E., Farber, E. A., Chang, S. Y., Hrycyna, C. A., Young, S. G., Fong, L. G. <strong>HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.</strong> Proc. Nat. Acad. Sci. 104: 13432-13437, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17652517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17652517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17652517[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0704212104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17652517">Coffinier et al. (2007)</a> concluded that HIV-PIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A, possibly explaining HIV-PI side effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17652517" 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>Prelamin A is normally prenylated at cys661 (C661), then proteolytically processed by ZMPSTE24 into mature lamin A with a C-terminal Y646 residue. By transfecting HEK293 cells with cDNAs encoding prelamin A with various point mutations, <a href="#94" class="mim-tip-reference" title="Pan, Y., Garg, A., Agarwal, A. K. <strong>Mislocalization of prelamin A Tyr646Phe mutant to the nuclear pore complex in human embryonic kidney 293 cells.</strong> Biochem. Biophys. Res. Commun. 355: 78-84, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17291448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17291448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17291448[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.bbrc.2007.01.116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17291448">Pan et al. (2007)</a> determined that prenylation at C661 was not necessary for proteolytic processing and targeting of mature lamin A to the nuclear lamina. However, prelamin A that was prenylated but could not be C-terminally processed by ZMPSTE24 mislocalized to the nuclear pore complex. Inhibition of prenylation resulted in correct targeting of mutant prelamin A, suggesting that prenylation itself contributed to mislocalization. Since inhibition of prenylation in cultured cells also inhibits accumulation of progerin at the nuclear pore complex, <a href="#94" class="mim-tip-reference" title="Pan, Y., Garg, A., Agarwal, A. K. <strong>Mislocalization of prelamin A Tyr646Phe mutant to the nuclear pore complex in human embryonic kidney 293 cells.</strong> Biochem. Biophys. Res. Commun. 355: 78-84, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17291448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17291448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17291448[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.bbrc.2007.01.116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17291448">Pan et al. (2007)</a> proposed that accumulation of prenylated protein at the nuclear pore complex causes nuclear dysmorphology and is cytotoxic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17291448" 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 nuclear envelope LINC (links the nucleoskeleton and cytoskeleton) complex, which is formed by SUN (e.g., SUN1, <a href="/entry/607723">607723</a>) and nesprin (e.g., SYNE1, <a href="/entry/608441">608441</a>) proteins, provides a direct connection between the nuclear lamina and the cytoskeleton. <a href="#47" class="mim-tip-reference" title="Haque, F., Mazzeo, D., Patel, J. T., Smallwood, D. T., Ellis, J. A., Shanahan, C. M., Shackleton, S. <strong>Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.</strong> J. Biol. Chem. 285: 3487-3498, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19933576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19933576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19933576[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M109.071910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19933576">Haque et al. (2010)</a> stated that SUN1 and SUN2 interact with LMNA and that LMNA is required for the nuclear envelope localization of SUN2, but not SUN1. They found that LMNA mutations associated with Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>) and HGPS disrupted interaction of LMNA with mouse Sun1 and human SUN2. Nuclear localization of SUN1 and SUN2 was not impaired in EDMD2 or HGPS cell lines. Expression of SUN1, but not SUN2, at the nuclear envelope was enhanced in some HGPS cells, likely due to increased interaction of SUN1 with accumulated prelamin A. <a href="#47" class="mim-tip-reference" title="Haque, F., Mazzeo, D., Patel, J. T., Smallwood, D. T., Ellis, J. A., Shanahan, C. M., Shackleton, S. <strong>Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.</strong> J. Biol. Chem. 285: 3487-3498, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19933576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19933576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19933576[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M109.071910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19933576">Haque et al. (2010)</a> proposed that different perturbations in LMNA-SUN protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19933576" 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>Nuclei are precisely positioned in skeletal muscle, with a small number clustered under neuromuscular junctions, and the remainder equally spaced along the periphery of the fiber. By screening 16 different disease-causing lamin A variants, <a href="#35" class="mim-tip-reference" title="Folker, E. S., Ostlund, C., Luxton, G. W. G., Worman, H. J., Gundersen, G. G. <strong>Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement.</strong> Proc. Nat. Acad. Sci. 108: 131-136, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173262</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21173262[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1000824108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21173262">Folker et al. (2011)</a> found that nearly all variants affected microtubule-dependent centrosome orientation, but only those that caused striated muscle disease disturbed actin-dependent nuclear movement and positioning. Wildtype, but not mutant, lamin A anchored SUN- and nesprin-containing LINC complexes that attach nuclei to retrogradely moving actin filaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21173262" 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="#70" 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. <strong>Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.</strong> Nature 472: 221-225, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21346760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21346760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21346760[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#70" 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. <strong>Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.</strong> Nature 472: 221-225, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21346760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21346760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21346760[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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><a href="#18" class="mim-tip-reference" title="Chen, C.-Y., Chi, Y.-H., Mutalif, R. A., Starost, M. F., Myers, T. G., Anderson, S. A., Stewart, C. L., Jeang, K.-T. <strong>Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.</strong> Cell 149: 565-577, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22541428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22541428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22541428[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.01.059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22541428">Chen et al. (2012)</a> showed that cells from Lmna -/- mice, which represent EDMD2, cells from Lmna(L530P/L530P) mice, which represent HGPS, and cells from HGPS patients all had overaccumulation of the inner nuclear envelope SUN1 protein. In wildtype cells, Lmna and Sun1 colocalized at the nuclear envelope. In Lmna -/- cells, larger amounts of Sun1 were found at the nuclear envelope and also in the Golgi. The larger amounts of Sun1 appeared to result from reduced protein turnover. Transfection of increasing amounts of mouse Sun1 into Lmna-null/Sun1-null murine cells resulted in increased prevalence of nuclear herniations and apoptosis, and the herniations appeared to result from Sun1 accumulation in the Golgi. Loss of the Sun1 gene in both mouse models extensively rescued cellular, tissue, organ, and lifespan abnormalities. Similarly, knockdown of overaccumulated SUN1 protein in primary human HGPS cells corrected nuclear defects and cellular senescence. The findings indicated that accumulation of SUN1 is a common pathogenetic event in these disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22541428" 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="Jung, H.-J., Coffinier, C., Choe, Y., Beigneux, A. P., Davies, B. S. J., Yang, S. H., Barnes, R. H., II, Hong, J., Sun, T., Pleasure, S. J., Young, S. G., Fong, L. G. <strong>Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA.</strong> Proc. Nat. Acad. Sci. 109: E423-E431, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22308344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22308344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22308344[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1111780109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22308344">Jung et al. (2012)</a> found that mouse prelamins A and C both contain at least 1 binding site for microRNA-9 (MIR9; <a href="/entry/611186">611186</a>) in their 3-prime UTRs. Mir9 downregulated lamin A expression by reducing prelamin A mRNA, but it did not downregulate lamin C expression. The findings suggested that high expression of Mir9 causes the low amount of lamin A, relative to lamin C, in mouse brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22308344" 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 knockin mice expressing prelamin A with alterations in its 3-prime UTR, <a href="#59" class="mim-tip-reference" title="Jung, H.-J., Tu, Y., Yang, S. H., Tatar, A., Nobumori, C., Wu, D., Young, S. G., Fong, L. G. <strong>New Lmna knock-in mice provide a molecular mechanism for the 'segmental aging' in Hutchinson-Gilford progeria syndrome.</strong> Hum. Molec. Genet. 23: 1506-1515, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24203701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24203701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24203701[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24203701">Jung et al. (2014)</a> showed that Mir9 repressed lamin A expression in cerebral cortex and cerebellum. Mutation of the Mir9-binding site in the 3-prime UTR of prelamin A or replacement of the 3-prime UTR of prelamin A with that of prelamin C resulted in enhanced lamin A expression in brain. <a href="#59" class="mim-tip-reference" title="Jung, H.-J., Tu, Y., Yang, S. H., Tatar, A., Nobumori, C., Wu, D., Young, S. G., Fong, L. G. <strong>New Lmna knock-in mice provide a molecular mechanism for the 'segmental aging' in Hutchinson-Gilford progeria syndrome.</strong> Hum. Molec. Genet. 23: 1506-1515, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24203701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24203701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24203701[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24203701">Jung et al. (2014)</a> proposed that reduced expression of prelamin A in brain might explain why children with HGPS are spared neurodegenerative disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24203701" 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 mice, <a href="#54" class="mim-tip-reference" title="Ho, C. Y., Jaalouk, D. E., Vartiainen, M. K., Lammerding, J. <strong>Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.</strong> Nature 497: 507-511, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23644458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23644458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23644458[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23644458">Ho et al. (2013)</a> found that lamin A/C-deficient (Lmna-null) and Lmna(N195K/N195K) (see <a href="#0007">150330.0007</a>) mutant cells have impaired nuclear translocation and downstream signaling of the mechanosensitive transcription factor megakaryoblastic leukemia-1 (MKL1; <a href="/entry/606078">606078</a>), a myocardin family member that is pivotal in cardiac development and function. Altered nucleocytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna-null and Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin (<a href="/entry/300384">300384</a>), which is mislocalized in Lmna mutant cells and also linked to Emery-Dreifuss muscular dystrophy (<a href="/entry/310300">310300</a>) and dilated cardiomyopathy, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. <a href="#54" class="mim-tip-reference" title="Ho, C. Y., Jaalouk, D. E., Vartiainen, M. K., Lammerding, J. <strong>Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.</strong> Nature 497: 507-511, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23644458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23644458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23644458[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23644458">Ho et al. (2013)</a> concluded that their findings presented a novel mechanism that could provide insight into the disease etiology for the cardiac phenotype in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23644458" 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="#114" class="mim-tip-reference" title="Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L. <strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong> Molec. Biol. Cell 24: 342-350, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23243001">Simon et al. (2013)</a> hypothesized that extensive posttranslational modification of mature lamin A may regulate its interactions with its binding partners, including actin, titin (TTN; <a href="/entry/188840">188840</a>), emerin, and SREBP1. They found that lys420 (K420) and K486 in lamin A were modified by SUMO1. K420 lies within the nuclear localization signal, and K486 lies within the immunoglobulin (Ig)-fold. <a href="#114" class="mim-tip-reference" title="Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L. <strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong> Molec. Biol. Cell 24: 342-350, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23243001">Simon et al. (2013)</a> proposed that SUMO modification of K420 might inhibit lamin A/C binding to cyclin D3 (CCND3; <a href="/entry/123834">123834</a>) or core histones that require an unmodified nuclear localization signal, or that it might inhibit binding of lamin A/C to alpha-importin (see <a href="/entry/600686">600686</a>). They suggested that SUMO1 modification of K486 might block partners that require an unmodified Ig-fold. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23243001" 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 in situ proximity ligation assays, reporter gene assays, and biochemical analysis, <a href="#122" class="mim-tip-reference" title="Vadrot, N., Duband-Goulet, I., Cabet, E., Attanda, W., Barateau, A., Vicart, P., Gerbal, F., Briand, N., Vigouroux, C., Oldenburg, A. R., Lund, E. G., Collas, P., Buendia, B. <strong>The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 24: 2096-2109, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25524705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25524705</a>] [<a href="https://doi.org/10.1093/hmg/ddu728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25524705">Vadrot et al. (2015)</a> found that the interaction of SREBP1 with lamin A and lamin C occurs at the nuclear periphery and in the nucleoplasm. Interactions involved the Ig fold common to preLMNA, LMNA, and LMNC, and were stronger when SREBP1 was bound to sterol response elements (SREs) in DNA. SREBP1, LMNA, and SREs formed ternary complexes in vitro. The interaction was inhibitory, and overexpression of A-type lamins reduced transcriptional activity of SREBP1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25524705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Reviews</em></strong></p><p>
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<a href="#108" class="mim-tip-reference" title="Schreiber, K. H., Kennedy, B. K. <strong>When lamins go bad: nuclear structure and disease.</strong> Cell 152: 1365-1375, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23498943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23498943</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23498943[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2013.02.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23498943">Schreiber and Kennedy (2013)</a> reviewed the disorders caused by mutations in nuclear lamins and other proteins of the nuclear envelope as well as the mechanisms underlying disease pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23498943" 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>Mutations in the LMNA gene cause a wide range of human diseases. Since more than 10 different clinical syndromes have been attributed to LMNA mutations, many of which show overlapping features, attempts at broad classification have been proposed. <a href="#136" class="mim-tip-reference" title="Worman, H. J., Bonne, G. <strong>'Laminopathies': a wide spectrum of human diseases.</strong> Exp. Cell Res. 313: 2121-2133, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17467691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17467691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17467691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.yexcr.2007.03.028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17467691">Worman and Bonne (2007)</a> suggested that the disorders may be classified into 4 major types: diseases of striated and cardiac muscle; lipodystrophy syndromes; peripheral neuropathy; and premature aging. <a href="#4" class="mim-tip-reference" title="Benedetti, S., Menditto, I., Degano, M., Rodolico, C., Merlini, L., D'Amico, A., Palmucci, L., Berardinelli, A., Pegoraro, E., Trevisan, C. P., Morandi, L., Moroni, I., and 15 others. <strong>Phenotypic clustering of lamin A/C mutations in neuromuscular patients.</strong> Neurology 69: 1285-1292, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377071</a>] [<a href="https://doi.org/10.1212/01.wnl.0000261254.87181.80" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377071">Benedetti et al. (2007)</a> suggested 2 main groups: (1) neuromuscular and cardiac disorders, and (2) lipodystrophy and premature aging disorders. The phenotypic heterogeneity of diseases resulting from a mutation in a single gene can be explained by the numerous roles of the nuclear lamina, including maintenance of nuclear shape and structure, as well as functional roles in transcriptional regulation and heterochromatin organization (review by <a href="#14" class="mim-tip-reference" title="Capell, B. C., Collins, F. S. <strong>Human laminopathies: nuclei gone genetically awry.</strong> Nature Rev. Genet. 7: 940-952, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17139325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17139325</a>] [<a href="https://doi.org/10.1038/nrg1906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17139325">Capell and Collins, 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17139325+17467691+17377071" 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="Genschel, J., Schmidt, H. H.-J. <strong>Mutations in the LMNA gene encoding lamin A/C.</strong> Hum. Mutat. 16: 451-459, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11102973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11102973</a>] [<a href="https://doi.org/10.1002/1098-1004(200012)16:6<451::AID-HUMU1>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11102973">Genschel and Schmidt (2000)</a> compiled a list of 41 known mutations, predominantly missense, in the LMNA gene. Twenty-three different mutations had been shown to cause autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>). Three mutations had been reported to cause what was formerly designated autosomal dominant limb-girdle muscular dystrophy (LGMD1B), reclassified as EDMD2 by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>. Eight mutations were known to result in dilated cardiomyopathy (CMD1A; <a href="/entry/115200">115200</a>), and 7 mutations were reported to cause familial partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>). In addition, 1 mutation in LMNA (H222Y; <a href="#0014">150330.0014</a>) appeared to be responsible for an autosomal recessive, atypical form of Emery-Dreifuss muscular dystrophy (EDMD3; <a href="/entry/616516">616516</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11102973+30055862" 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>Muscular Dystrophies</em></strong></p><p>
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In 5 families with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), <a href="#6" class="mim-tip-reference" title="Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K. <strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong> Nature Genet. 21: 285-288, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>] [<a href="https://doi.org/10.1038/6799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080180">Bonne et al. (1999)</a> identified 4 mutations in the LMNA gene (<a href="#0001">150330.0001</a>-<a href="#0004">150330.0004</a>) that cosegregated with the disease phenotype. These findings represented the first identification of mutations in a component of the nuclear lamina as a cause of an inherited muscle disorder. The authors noted that lamins interact with integral proteins of the inner nuclear membrane, including emerin (<a href="/entry/300384">300384</a>), which is mutated in the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD1; <a href="/entry/310300">310300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" 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="#97" class="mim-tip-reference" title="Raffaele di Barletta, M., Ricci, E., Galluzzi, G., Tonali, P., Mora, M., Morandi, L., Romorini, A., Voit, T., Orstavik, K. H., Merlini, L., Trevisan, C., Biancalana, V., Housmanowa-Petrusewicz, I., Bione, S., Ricotti, R., Schwartz, K., Bonne, G., Toniolo, D. <strong>Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 66: 1407-1412, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739764">Raffaele di Barletta et al. (2000)</a> showed that heterozygous mutations in LMNA may cause diverse phenotypes ranging from typical EDMD to no phenotypic effect. LMNA mutations in patients with autosomal dominant EDMD occur in the tail and in the 2A rod domain of the protein, suggesting that unique interactions between lamin A/C and other nuclear components have an important role in cardiac and skeletal muscle function. They identified a homozygous LMNA mutation (H222Y; <a href="#0014">150330.0014</a>) in 1 patient born of consanguineous unaffected parents, consistent with autosomal recessive inheritance (EDMD3) and a severe atypical phenotype lacking cardiac features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10739764" 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="#87" class="mim-tip-reference" title="Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K. <strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong> Hum. Molec. Genet. 9: 1453-1459, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814726</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814726">Muchir et al. (2000)</a> found mutations in the LMNA gene in 3 families with LGMD1B, reclassified as EDMD2 by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>: a missense mutation (<a href="#0017">150330.0017</a>), a deletion of a codon (<a href="#0018">150330.0018</a>), and a splice donor site mutation (<a href="#0019">150330.0019</a>). The 3 mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10814726+30055862" 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="#96" class="mim-tip-reference" title="Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others. <strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong> Ann. Neurol. 64: 177-186, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>] [<a href="https://doi.org/10.1002/ana.21417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551513">Quijano-Roy et al. (2008)</a> described a form of congenital muscular dystrophy (MDC) with onset in the first year of life in 15 children resulting from de novo heterozygous mutations in the LMNA gene (see, e.g., <a href="#0047">150330.0047</a>-<a href="#0049">150330.0049</a>). Three patients had severe early-onset disease, with decreased fetal movements in utero, no motor development, severe hypotonia, diffuse limb and axial muscle weakness and atrophy, and talipes foot deformities. The remaining 12 children initially acquired head and trunk control and independent ambulation, but most lost head control due to neck extensor weakness, a phenotype consistent with 'dropped head syndrome.' Ten children required ventilatory support. Cardiac arrhythmias were observed in 4 of the oldest patients, but were symptomatic only in 1. <a href="#96" class="mim-tip-reference" title="Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others. <strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong> Ann. Neurol. 64: 177-186, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>] [<a href="https://doi.org/10.1002/ana.21417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551513">Quijano-Roy et al. (2008)</a> concluded that the identified LMNA mutations appeared to correlate with a relatively severe phenotype, broadening the spectrum of laminopathies. The authors suggested that this group of patients may define a new disease entity, which they designated LMNA-related congenital muscular dystrophy (<a href="/entry/613205">613205</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Benedetti, S., Menditto, I., Degano, M., Rodolico, C., Merlini, L., D'Amico, A., Palmucci, L., Berardinelli, A., Pegoraro, E., Trevisan, C. P., Morandi, L., Moroni, I., and 15 others. <strong>Phenotypic clustering of lamin A/C mutations in neuromuscular patients.</strong> Neurology 69: 1285-1292, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377071</a>] [<a href="https://doi.org/10.1212/01.wnl.0000261254.87181.80" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377071">Benedetti et al. (2007)</a> reported 27 individuals with mutations in the LMNA gene resulting in a wide range of neuromuscular disorders. Phenotypic analysis yielded 2 broad groups of patients. One group included patients with childhood onset who had skeletal muscle involvement with predominant scapuloperoneal and facial weakness, consistent with EDMD or congenital muscular dystrophy. The second group included patients with later or adult onset who had cardiac disorders or a limb-girdle myopathy, consistent with LGMD1B. Those in the group with early onset tended to have missense mutations, whereas those in the group with adult onset tended to have truncating mutations. Analysis of the variants showed that those associated with early-onset phenotypes were primarily found in the Ig-like domain and in coil 2A, which may interfere with binding to specific ligands. Those associated with later onset were mostly located in the rod domain and in coil 2B, which was predicted to affect the surface of lamin A/C dimers and lead to impaired filament assembly. <a href="#4" class="mim-tip-reference" title="Benedetti, S., Menditto, I., Degano, M., Rodolico, C., Merlini, L., D'Amico, A., Palmucci, L., Berardinelli, A., Pegoraro, E., Trevisan, C. P., Morandi, L., Moroni, I., and 15 others. <strong>Phenotypic clustering of lamin A/C mutations in neuromuscular patients.</strong> Neurology 69: 1285-1292, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377071</a>] [<a href="https://doi.org/10.1212/01.wnl.0000261254.87181.80" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377071">Benedetti et al. (2007)</a> speculated that there may be 2 different pathogenetic mechanisms associated with neuromuscular LMNA-related disorders: late-onset phenotypes may arise through loss of LMNA function secondary to haploinsufficiency, whereas dominant-negative or toxic gain-of-function mechanisms may underlie the more severe early phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377071" 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="#106" class="mim-tip-reference" title="Scharner, J., Brown, C. A., Bower, M., Iannaccone, S. T., Khatri, I. A., Escolar, D., Gordon, E., Felice, K., Crowe, C. A., Grosmann, C., Meriggioli, M. N., Asamoah, A., Gordon, O., Gnocchi, V. F., Ellis, J. A., Mendell, J. R., Zammit, P. S. <strong>Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.</strong> Hum. Mutat. 32: 152-167, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20848652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20848652</a>] [<a href="https://doi.org/10.1002/humu.21361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20848652">Scharner et al. (2011)</a> identified LMNA mutations in 61 (23.9%) of 255 patients with muscular dystrophy. Eleven of the patients had previously been reported by <a href="#9" class="mim-tip-reference" title="Brown, C. A., Lanning, R. W., McKinney, K. Q., Salvino, A. R., Cherniske, E., Crowe, C. A., Darras, B. T., Gominak, S., Greenberg, C. R., Grosmann, C., Heydemann, P., Mendell, J. R., Pober, B. R., Sasaki, T., Shapiro, F., Simpson, D. A., Suchowersky, O., Spence, J. E. <strong>Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.</strong> Am. J. Med. Genet. 102: 359-367, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11503164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11503164</a>] [<a href="https://doi.org/10.1002/ajmg.1463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11503164">Brown et al. (2001)</a>. Among the remaining 50 patients from the United States and Canada, <a href="#106" class="mim-tip-reference" title="Scharner, J., Brown, C. A., Bower, M., Iannaccone, S. T., Khatri, I. A., Escolar, D., Gordon, E., Felice, K., Crowe, C. A., Grosmann, C., Meriggioli, M. N., Asamoah, A., Gordon, O., Gnocchi, V. F., Ellis, J. A., Mendell, J. R., Zammit, P. S. <strong>Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.</strong> Hum. Mutat. 32: 152-167, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20848652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20848652</a>] [<a href="https://doi.org/10.1002/humu.21361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20848652">Scharner et al. (2011)</a> found 37 mutations, including 15 novel ones. The mutations were scattered throughout the gene. In vitro functional expression studies performed on some of the mutations (e.g., R249W; <a href="#0048">150330.0048</a>) showed that they resulted in increased expression of mutant LMNA, mislocalization of the protein in the nucleus, abnormal nuclear morphology with lobules, and mislocalization of lamin B (LMNB; <a href="/entry/150340">150340</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20848652+11503164" 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 sibs, born of consanguineous Spanish parents, with EDMD3, <a href="#57" class="mim-tip-reference" title="Jimenez-Escrig, A., Gobernado, I., Garcia-Villanueva, M., Sanchez-Herranz, A. <strong>Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing.</strong> Muscle Nerve 45: 605-610, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22431096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22431096</a>] [<a href="https://doi.org/10.1002/mus.22324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22431096">Jimenez-Escrig et al. (2012)</a> identified a homozygous missense mutation in the LMNA gene (R225Q; <a href="#0054">150330.0054</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in 200 control chromosomes. Functional studies of the variant were not performed. Two heterozygous carriers had no muscular symptoms, but developed cardiac arrhythmias late in life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22431096" 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 2 sibs from a family of Hutterite descent with EDMD3 and features of partial lipodystrophy, <a href="#135" class="mim-tip-reference" title="Wiltshire, K. M., Hegele, R. A., Innes, A. M., Brownell, A. K. W. <strong>Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.</strong> Neuromusc. Disord. 23: 265-268, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23313286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23313286</a>] [<a href="https://doi.org/10.1016/j.nmd.2012.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23313286">Wiltshire et al. (2013)</a> identified a homozygous missense mutation in the LMNA gene (R482Q; <a href="#0010">150330.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23313286" 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>Dilated Cardiomyopathy and Cardiac Conduction Defects</em></strong></p><p>
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<a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> studied the LMNA gene in 11 families with autosomal dominant dilated cardiomyopathy and conduction system disease (CMD1A; <a href="/entry/115200">115200</a>) linked to a region on chromosome 1 overlapping that of the LMNA gene. They identified 5 novel missense mutations (<a href="#0004">150330.0004</a>-<a href="#0009">150330.0009</a>): 4 in the alpha-helical rod domain of lamin A, and 1 in the tail domain of lamin C. No family members with mutations had joint contractures or skeletal myopathy characteristic of autosomal dominant Emery-Dreifuss muscular dystrophy. Furthermore, serum creatine kinase levels were normal in family members with mutations of the lamin A rod domain, but mildly elevated in some family members with a defect in the lamin C tail domain. The authors noted that mutations in the rod domain of the protein led to dilated cardiomyopathy, whereas mutations in the head or tail domain caused Emery-Dreifuss muscular dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" 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="#124" class="mim-tip-reference" title="van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M. <strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong> Neurology 59: 620-623, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196663</a>] [<a href="https://doi.org/10.1212/wnl.59.4.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12196663">Van der Kooi et al. (2002)</a> reported a sporadic patient and 2 unrelated families with mutations in the LMNA gene who presented with varying degrees and combinations of muscular dystrophy, partial lipodystrophy, and cardiomyopathy with conduction defects, presumably due to single mutations (see <a href="#0003">150330.0003</a> and <a href="#0005">150330.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12196663" 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="#109" class="mim-tip-reference" title="Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. <strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong> J. Med. Genet. 40: 560-567, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>] [<a href="https://doi.org/10.1136/jmg.40.8.560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920062">Sebillon et al. (2003)</a> screened the coding sequence of LMNA in DNA samples from 66 index cases of dilated cardiomyopathy with or without associated features. They identified a glu161-to-lys mutation (E161K; <a href="#0028">150330.0028</a>) in a family with early-onset atrial fibrillation preceding or coexisting with dilated cardiomyopathy, the previously described R377H mutation (<a href="#0017">150330.0017</a>) in the family with quadriceps myopathy associated with dilated cardiomyopathy previously reported by <a href="#17" class="mim-tip-reference" title="Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M. <strong>Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.</strong> Hum. Mutat. 21: 473-481, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673789</a>] [<a href="https://doi.org/10.1002/humu.10170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673789">Charniot et al. (2003)</a>, and a 28insA mutation (<a href="#0029">150330.0029</a>) leading to a premature stop codon in a third family with dilated cardiomyopathy with conduction defects. No mutation in LMNA was found in cases with isolated dilated cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12673789+12920062" 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="#81" class="mim-tip-reference" title="Meune, C., Van Berlo, J. H., Anselme, F., Bonne, G., Pinto, Y. M., Duboc, D. <strong>Primary prevention of sudden death in patients with lamin A/C gene mutations. (Letter)</strong> New Eng. J. Med. 354: 209-210, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407522</a>] [<a href="https://doi.org/10.1056/NEJMc052632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407522">Meune et al. (2006)</a> investigated the efficacy of implantable cardioverter-defibrillators (ICDs) in the primary prevention of sudden death in patients with cardiomyopathy due to lamin A/C gene mutations. Patients referred for permanent cardiac pacing were systematically offered the implantation of an ICD. The patients were enrolled solely on the basis of the presence of lamin A/C mutations associated with cardiac conduction defects. Indications for pacemaker implantation were progressive conduction block and sinus block. In all, 19 patients were treated. <a href="#81" class="mim-tip-reference" title="Meune, C., Van Berlo, J. H., Anselme, F., Bonne, G., Pinto, Y. M., Duboc, D. <strong>Primary prevention of sudden death in patients with lamin A/C gene mutations. (Letter)</strong> New Eng. J. Med. 354: 209-210, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407522</a>] [<a href="https://doi.org/10.1056/NEJMc052632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407522">Meune et al. (2006)</a> concluded that ICD implantation in patients with lamin A/C mutations who are in need of a pacemaker is effective in treating possibly lethal tachyarrhythmias, and that implantation of an ICD, rather than a pacemaker, should be considered for such patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16407522" 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="#119" class="mim-tip-reference" title="Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group. <strong>Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.</strong> J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12628721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12628721</a>] [<a href="https://doi.org/10.1016/s0735-1097(02)02954-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12628721">Taylor et al. (2003)</a> screened the LMNA gene in 40 families and 9 sporadic patients with CMD with or without muscular dystrophy and identified mutations in 3 families (see, e.g., <a href="#0017">150330.0017</a>) and 1 sporadic patient (S573L; <a href="#0041">150330.0041</a>). All mutations involved a conserved residue, cosegregated with the disease within the families, and were not found in 300 control chromosomes. LMNA mutation carriers had a severe and progressive form of CMD with significantly poorer cumulative survival compared to noncarrier CMD patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12628721" 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>Dilated Cardiomyopathy and Hypergonadotropic Hypogonadism</em></strong></p><p>
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In a 17-year-old Caucasian female with premature ovarian failure and dilated cardiomyopathy, who had features consistent with atypical Werner syndrome (see <a href="/entry/277700">277700</a>) but who was negative for mutation in the RECQL2 gene (<a href="/entry/604611">604611</a>), <a href="#92" class="mim-tip-reference" title="Nguyen, D., Leistritz, D. F., Turner, L., MacGregor, D., Ohson, K., Dancey, P., Martin, G. M., Oshima, J. <strong>Collagen expression in fibroblasts with a novel LMNA mutation.</strong> Biochem. Biophys. Res. Commun. 352: 603-608, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17150192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17150192</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17150192[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.11.070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17150192">Nguyen et al. (2007)</a> identified heterozygosity for a missense mutation in the LMNA gene (L59R; <a href="#0052">150330.0052</a>). The authors suggested the diagnosis of a laminopathy, most likely an atypical form of mandibuloacral dysplasia (see <a href="/entry/248370">248370</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17150192" 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 15-year-old Caucasian girl with premature ovarian failure and dilated cardiomyopathy, <a href="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> identified heterozygosity for the L59R mutation in the LMNA gene. <a href="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> noted phenotypic similarities between this patient and the patient previously reported by <a href="#92" class="mim-tip-reference" title="Nguyen, D., Leistritz, D. F., Turner, L., MacGregor, D., Ohson, K., Dancey, P., Martin, G. M., Oshima, J. <strong>Collagen expression in fibroblasts with a novel LMNA mutation.</strong> Biochem. Biophys. Res. Commun. 352: 603-608, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17150192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17150192</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17150192[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.11.070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17150192">Nguyen et al. (2007)</a>, who carried the same mutation, as well as a patient originally described by <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> with an adjacent A57P mutation in LMNA (<a href="#0030">150330.0030</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="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> suggested that the phenotype represents a distinct laminopathy involving dilated cardiomyopathy and hypergonadotropic hypogonadism (<a href="/entry/212112">212112</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19283854+12927431+17150192" 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>Lipodystrophy Disorders</em></strong></p><p>
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Patients with Dunnigan-type familial partial lipodystrophy, or partial lipodystrophy type 2 (FPLD2; <a href="/entry/151660">151660</a>), are born with normal fat distribution, but after puberty experience regional and progressive adipocyte degeneration, often associated with profound insulin resistance and diabetes. <a href="#11" class="mim-tip-reference" title="Cao, H., Hegele, R. A. <strong>Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 9: 109-112, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587585</a>] [<a href="https://doi.org/10.1093/hmg/9.1.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10587585">Cao and Hegele (2000)</a> hypothesized that the analogy between the regional muscle wasting in autosomal dominant Emery-Dreifuss muscular dystrophy and the regional adipocyte degeneration in FPLD, in addition to the chromosomal localization of the FPLD2 locus on 1q21-q22, made LMNA a good candidate gene for FPLD2. Studies of 5 Canadian probands with familial partial lipodystrophy of Dunnigan type indicated that each had a novel missense mutation (R482Q; <a href="#0010">150330.0010</a>) that cosegregated with the lipodystrophy phenotype and was absent from 2,000 normal alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587585" 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="#110" class="mim-tip-reference" title="Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C. <strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong> Nature Genet. 24: 153-156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655060</a>] [<a href="https://doi.org/10.1038/72807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655060">Shackleton et al. (2000)</a> identified 5 different missense mutations in the LMNA gene (see, e.g., <a href="#0010">150330.0010</a>-<a href="#0012">150330.0012</a>) among 10 kindreds and 3 individuals with partial lipodystrophy. All of the mutations occurred in exon 8, which the authors noted is within the C-terminal globular domain of lamin A/C. <a href="#34" class="mim-tip-reference" title="Flier, J. S. <strong>Pushing the envelope on lipodystrophy.</strong> Nature Genet. 24: 103-104, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655047</a>] [<a href="https://doi.org/10.1038/72734" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655047">Flier (2000)</a> commented on the significance of LMNA mutations in partial lipodystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10655060+10655047" 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="#129" class="mim-tip-reference" title="Vantyghem, M. C., Pigny, P., Maurage, C. A., Rouaix-Emery, N., Stojkovic, T., Cuisset, J. M., Millaire, A., Lascols, O., Vermersch, P., Wemeau, J. L., Capeau, J., Vigouroux, C. <strong>Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities.</strong> J. Clin. Endocr. Metab. 89: 5337-5346, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531479</a>] [<a href="https://doi.org/10.1210/jc.2003-031658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531479">Vantyghem et al. (2004)</a> characterized the neuromuscular and cardiac phenotypes of FPLD patients bearing the heterozygous R482W mutation. Fourteen patients from 2 unrelated families, including 10 affected subjects, were studied. Clinical and histologic examination showed an incapacitating, progressive limb-girdle muscular dystrophy in a 42-year-old woman that had been present since childhood, associated with a typical postpubertal FPLD phenotype. Six of 8 adults presented the association of calf hypertrophy, perihumeral muscular atrophy, and a rolling gait due to proximal lower limb weakness. Muscular histology was compatible with muscular dystrophy in one of them and/or showed a nonspecific excess of lipid droplets (in 3 cases). Cardiac septal hypertrophy and atherosclerosis were frequent in FPLD patients. In addition, a 24-year-old FPLD patient had a symptomatic second-degree atrioventricular block. <a href="#129" class="mim-tip-reference" title="Vantyghem, M. C., Pigny, P., Maurage, C. A., Rouaix-Emery, N., Stojkovic, T., Cuisset, J. M., Millaire, A., Lascols, O., Vermersch, P., Wemeau, J. L., Capeau, J., Vigouroux, C. <strong>Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities.</strong> J. Clin. Endocr. Metab. 89: 5337-5346, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531479</a>] [<a href="https://doi.org/10.1210/jc.2003-031658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531479">Vantyghem et al. (2004)</a> concluded that most lipodystrophic patients affected by the FPLD-linked R482W mutation show muscular and cardiac abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531479" 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>Mandibuloacral dysplasia (see <a href="/entry/248370">248370</a>) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. Patients with MAD frequently have partial lipodystrophy and insulin resistance, which are features seen in FPLD. In all affected members of 5 consanguineous Italian families with MAD, <a href="#93" class="mim-tip-reference" title="Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M. R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G. <strong>Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.</strong> Am. J. Hum. Genet. 71: 426-431, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075506</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12075506[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/341908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075506">Novelli et al. (2002)</a> identified a homozygous missense mutation (R527H; <a href="#0021">150330.0021</a>) in the LMNA gene. Patient skin fibroblasts showed nuclei that presented abnormal lamin A/C distribution and a dysmorphic envelope, demonstrating the pathogenic effect of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075506" 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 consanguineous family from north India, <a href="#95" 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. <strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 609-614, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15286156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15286156</a>] [<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15286156">Plasilova et al. (2004)</a> identified a homozygous missense mutation in the LMNA gene (<a href="#0033">150330.0033</a>). The extent of skeletal lesions in this family were consistent with MAD, but affected individuals also had classic features of progeria. <a href="#95" 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. <strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 609-614, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15286156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15286156</a>] [<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15286156">Plasilova et al. (2004)</a> suggested that autosomal recessive HGPS and mandibuloacral dysplasia may represent a single disorder with varying degrees of disease 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><p><a href="#29" class="mim-tip-reference" title="Decaudain, A., Vantyghem, M.-C., Guerci, B., Hecart, A.-C., Auclair, M., Reznik, Y., Narbonne, H., Ducluzeau, P.-H., Donadille, B., Lebbe, C., Bereziat, V., Capeau, J., Lascols, O., Vigouroux, C. <strong>New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.</strong> J. Clin. Endocr. Metab. 92: 4835-4844, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17711925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17711925</a>] [<a href="https://doi.org/10.1210/jc.2007-0654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17711925">Decaudain et al. (2007)</a> identified changes in codon 482 of the LMNA gene (see, e.g., R482Q, <a href="#0010">150330.0010</a> and R482W, <a href="#0011">150330.0011</a>) in 17 of 277 unrelated adults investigated for lipodystrophy and/or insulin resistance. All 17 had classic features of FPLD2. Ten additional patients who fulfilled the International Diabetes Federation diagnostic criteria for metabolic syndrome were found to have heterozygous LMNA mutations that were not in codon 482, but affected all 3 domains of the protein, the N terminal, central rod domain, and C terminal globulin domain (see, e.g., R399C; <a href="#0043">150330.0043</a>). Because the phenotype of these patients was not typical of FPLD2, the diagnosis of laminopathy was delayed. Although lipodystrophy was less severe than in typical FPLD2, common features included calf hypertrophy, myalgia, and muscle cramps or weakness. Two patients had cardiac conduction disturbances. Metabolic alterations were prominent, especially insulin resistance and hypertriglyceridemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17711925" 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>Charcot-Marie-Tooth Disease Type 2B1</em></strong></p><p>
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In affected members of inbred Algerian families with an axonal form of Charcot-Marie-Tooth disease linked to chromosome 1q21.2-q21.3 (CMT2B1; <a href="/entry/605588">605588</a>), <a href="#28" class="mim-tip-reference" title="De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N. <strong>Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.</strong> Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799477</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11799477[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799477">De Sandre-Giovannoli et al. (2002)</a> found a shared common homozygous ancestral haplotype that was suggestive of a founder mutation and identified a unique mutation in the LMNA rod domain (R298C; <a href="#0020">150330.0020</a>). Ultrastructural studies of sciatic nerves of Lmna-null mice showed a strong reduction of axon density, axonal enlargement, and the presence of nonmyelinated axons, all of which were highly similar to the phenotypes of human peripheral axonopathies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799477" 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>Hutchinson-Gilford Progeria Syndrome and Other Premature Aging Syndromes</em></strong></p><p>
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<a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> identified de novo heterozygous point mutations in lamin A that cause Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>). Eighteen of 20 classic cases of HGPS harbored the identical de novo single-base substitution resulting in a silent gly-to-gly change at codon 608 within exon 11 (<a href="#0022">150330.0022</a>). This change creates an exonic consensus splice site and activates cryptic splicing, leading to deletion of 50 codons at the end of prelamin A. This prelamin A still retains the CAAX box but lacks the site for endoproteolytic cleavage. <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> suggested that there is at least 1 site for phosphorylation, ser625, that is deleted in the abnormal lamin A protein. <a href="#27" 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. <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://doi.org/10.1126/science.1084125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702809">De Sandre-Giovannoli et al. (2003)</a> independently identified the heterozygous exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del; <a href="#0022">150330.0022</a>) in 2 HGPS patients. Later cellular studies (<a href="#15" class="mim-tip-reference" title="Capell, B. C., Erdos, M. R., Madigan, J. P., Fiordalisi, J. J., Varga, R., Conneely, K. N., Gordon, L. B., Der, C. J., Cox, A. D., Collins, F. S. <strong>Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 102: 12879-12884, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129833</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129833[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0506001102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16129833">Capell et al., 2005</a>; <a href="#42" class="mim-tip-reference" title="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> Hum. Molec. Genet. 14: 2959-2969, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16126733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16126733</a>] [<a href="https://doi.org/10.1093/hmg/ddi326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16126733">Glynn and Glover, 2005</a>; <a href="#121" class="mim-tip-reference" title="Toth, J. I., Yang, S. H., Qiao, X., Beigneux, A. P., Gelb, M. H., Moulson, C. L., Miner, J. H., Young, S. G., Fong, L. G. <strong>Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.</strong> Proc. Nat. Acad. Sci. 102: 12873-12878, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0505767102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16129834">Toth et al., 2005</a>) indicated that Hutchinson-Gilford progeria syndrome results from the production of a truncated prelamin A, called progerin, which is farnesylated at its C terminus and accumulates at the nuclear envelope, causing misshapen nuclei (<a href="#141" 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. <strong>A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.</strong> J. Clin. Invest. 116: 2115-2121, 2006.[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://doi.org/10.1172/JCI28968" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16862216">Yang et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12714972+12702809+16862216+16126733+16129834+16129833" 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>Werner syndrome (<a href="/entry/277700">277700</a>) is an autosomal recessive progeroid syndrome caused by mutation in the RECQL2 gene (WRN; <a href="/entry/604611">604611</a>). <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> reported that of 129 index patients referred to their international registry for molecular diagnosis of Werner syndrome, 26 (20%) had wildtype RECQL2 coding regions and were categorized as having 'atypical Werner syndrome' or 'non-WRN' on the basis of molecular criteria. Because of some phenotypic similarities between Werner syndrome and laminopathies including Hutchinson-Gilford progeria, <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> sequenced all exons of the LMNA gene in these 26 individuals and found heterozygosity for novel missense mutations in LMNA in 4 (15%): A57P (<a href="#0030">150330.0030</a>), R133L (<a href="#0027">150330.0027</a>) in 2 persons, and L140R (<a href="#0031">150330.0031</a>). <a href="#51" class="mim-tip-reference" title="Hegele, R. A. <strong>Drawing the line in progeria syndromes.</strong> Lancet 362: 416-417, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14097-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927424">Hegele (2003)</a> stated that the clinical designation of Werner syndrome for each of the 4 patients of <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a>, in whom mutations in the LMNA gene were found, 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 Hutchinson-Gilford syndrome as with early-onset Werner syndrome. Patients with so-called atypical Werner syndrome and mutant LMNA also expressed components of nonprogeroid laminopathies. <a href="#51" class="mim-tip-reference" title="Hegele, R. A. <strong>Drawing the line in progeria syndromes.</strong> Lancet 362: 416-417, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14097-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> suggested that the patient in whom <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> identified an A57P LMNA mutation had a distinct phenotype involving 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="#23" class="mim-tip-reference" title="Csoka, A. B., Cao, H., Sammak, P. J., Constantinescu, D., Schatten, G. P., Hegele, R. A. <strong>Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.</strong> J. Med. Genet. 41: 304-308, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060110</a>] [<a href="https://doi.org/10.1136/jmg.2003.015651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060110">Csoka et al. (2004)</a> screened 13 cell lines from atypical progeroid patients for mutation in the LMNA gene. They identified 3 novel heterozygous missense mutations in the LMNA gene in 3 patients: a 13-year-old female with a progeroid syndrome, a 15-year-old male with a lipodystrophy, and a 20-year-old male with 'atypical progeria.' The mutations identified in the last 2 patients were the most 5-prime and 3-prime missense mutations, respectively, that had been identified in LMNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060110" 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="#99" class="mim-tip-reference" title="Reddel, C. J., Weiss, A. S. <strong>Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 715-717, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342704</a>] [<a href="https://doi.org/10.1136/jmg.2004.019323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342704">Reddel and Weiss (2004)</a> reported that transcription efficiencies of the mutant and wildtype LMNA alleles were equivalent in HGPS. The mutant allele gave 2 types of transcripts that encoded truncated and normal lamin A. Abnormally spliced progerin transcript constituted the majority (84.5%) of the total steady-state mRNA derived from the mutant allele. The abnormally spliced progerin transcript was a minority (40%) of all lamin A transcripts obtained from both alleles. <a href="#99" class="mim-tip-reference" title="Reddel, C. J., Weiss, A. S. <strong>Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 715-717, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342704</a>] [<a href="https://doi.org/10.1136/jmg.2004.019323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342704">Reddel and Weiss (2004)</a> concluded that the mutated progerin functions as a dominant negative by interfering with the structure of the nuclear lamina, intranuclear architecture, and macromolecular interactions, which collectively would have a major impact on nuclear function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342704" 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>Fibroblasts from individuals with HGPS have severe morphologic abnormalities in nuclear envelope structure. <a href="#103" class="mim-tip-reference" title="Scaffidi, P., Misteli, T. <strong>Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.</strong> Nature Med. 11: 440-445, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15750600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15750600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15750600[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm1204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15750600">Scaffidi and Misteli (2005)</a> showed that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wildtype lamin A protein did not rescue the cellular disease manifestations. The mutant LMNA mRNA and lamin A protein could be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assumed normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins were rescued, defects in heterochromatin-specific histone modifications were corrected, and proper expression of several misregulated genes was reestablished. The results established proof of principle for the correction of the premature aging phenotype in individuals with HGPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15750600" 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="#55" class="mim-tip-reference" title="Huang, S., Chen, L., Libina, N., Janes, J., Martin, G. M., Campisi, J., Oshima, J. <strong>Correction of cellular phenotypes of Hutchinson-Gilford progeria cells by RNA interference.</strong> Hum. Genet. 118: 444-450, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16208517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16208517</a>] [<a href="https://doi.org/10.1007/s00439-005-0051-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16208517">Huang et al. (2005)</a> designed short hairpin RNAs (shRNA) targeting mutated pre-spliced or mature LMNA mRNAs and expressed them in HGPS fibroblasts carrying the 1824C-T mutation (<a href="#0022">150330.0022</a>). One of the shRNAs reduced the expression levels of mutant lamin A (so-called LA delta-50) to 26% or lower. The reduced expression was associated with amelioration of abnormal nuclear morphology, improvement of proliferative potential, and reduction in the numbers of senescent cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16208517" 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="#84" 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. <strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong> Hum. Mutat. 28: 882-889, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>] [<a href="https://doi.org/10.1002/humu.20536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#0036">150330.0036</a> and <a href="#0040">150330.0040</a>, respectively). Both mutations resulted in increased use of the cryptic exon 11 donor splice site that is also observed with the common 1824C-T mutation (<a href="#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 with severity of 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><a href="#105" class="mim-tip-reference" title="Scaffidi, P., Misteli, T. <strong>Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.</strong> Nature Cell Biol. 10: 452-459, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18311132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18311132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18311132[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ncb1708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18311132">Scaffidi and Misteli (2008)</a> found that progerin (<a href="#0022">150330.0022</a>) expression in immortalized human skin fibroblasts produced several defects typical of HGPS. Progerin also caused the spontaneous differentiation of human mesenchymal stem cells (MSCs) into endothelial cells, and reduced their differentiation along the adipogenic lineage. Abnormal differentiation of MSCs appeared to be due to progerin-induced activation of major downstream effectors of the Notch signaling pathway, including HES1 (<a href="/entry/139605">139605</a>), HES5 (<a href="/entry/607348">607348</a>), and HEY1 (<a href="/entry/602953">602953</a>). <a href="#105" class="mim-tip-reference" title="Scaffidi, P., Misteli, T. <strong>Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.</strong> Nature Cell Biol. 10: 452-459, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18311132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18311132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18311132[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ncb1708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18311132">Scaffidi and Misteli (2008)</a> noted that the progerin splice variant of LMNA is present at low levels in cells from healthy individuals and has been implicated in the normal aging process. They suggested that progerin-induced defects in Notch signaling are involved in normal aging and similarly affect adult MSCs and their differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18311132" 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 nonconsanguineous family with an atypical form of HGPS manifest as adult-onset coronary disease and progeroid features, <a href="#53" 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. <strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong> Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.34336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065502">Hisama et al. (2011)</a> identified a heterozygous splice site mutation affecting exon 11 of the LMNA gene (c.1968G-A; <a href="#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="#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. <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>In affected members of a family with a protracted form of HGPS (see <a href="/entry/176670">176670</a>) manifest as premature cutaneous and cardiac aging in young adulthood, <a href="#61" 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. <strong>LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.</strong> Am. J. Med. Genet. 161A: 1599-1611, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23666920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23666920</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.35971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23666920">Kane et al. (2013)</a> identified a heterozygous missense mutation in the LMNA gene (D300G; <a href="#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><strong><em>Restrictive Dermopathy 2</em></strong></p><p>
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In 2 of 9 patients with restrictive dermopathy (RSMD2; <a href="/entry/619793">619793</a>), a lethal genodermatosis in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence, <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> identified heterozygous splicing mutations in the LMNA gene, resulting in the complete or partial loss of exon 11 (<a href="#0036">150330.0036</a> and <a href="#0022">150330.0022</a>, respectively). In the other 7 patients, they identified a heterozygous 1-bp duplication resulting in a premature stop codon in the zinc metalloproteinase STE24 gene (ZMPSTE24; <a href="/entry/606480">606480</a>). This gene encodes a metalloproteinase specifically involved in the posttranslational processing of lamin A precursor. In all patients carrying a ZMPSTE24 mutation, loss of expression of lamin A as well as abnormal patterns of nuclear sizes and shapes and mislocalization of lamin-associated proteins was seen. <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> concluded that a common pathogenetic pathway, involving defects of the nuclear lamina and matrix, is involved in restrictive dermopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=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="#90" class="mim-tip-reference" title="Navarro, C. L., Cadinanos, J., De Sandre-Giovannoli, A., Bernard, R., Courrier, S., Boccaccio, I., Boyer, A., Kleijer, W. J., Wagner, A., Giuliano, F., Beemer, F. A., Freije, J. M., Cau, P., Hennekam, R. C. M., Lopez-Otin, C., Badens, C., Levy, N. <strong>Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors.</strong> Hum. Molec. Genet. 14: 1503-1513, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843403</a>] [<a href="https://doi.org/10.1093/hmg/ddi159" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843403">Navarro et al. (2005)</a> described 7 previously reported patients and 3 new patients with restrictive dermopathy who were homozygous or compound heterozygous for ZMPSTE24 mutations. In all cases there was complete absence of both ZMPSTE24 and mature lamin A, associated with prelamin A accumulation. The authors concluded that restrictive dermopathy is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations. The accumulation of truncated or normal length prelamin A is, therefore, a shared pathophysiologic feature in recessive and dominant restrictive dermopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843403" 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>Heart-Hand Syndrome, Slovenian Type</em></strong></p><p>
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In a Slovenian family with heart-hand syndrome (<a href="/entry/610140">610140</a>), originally reported by <a href="#116" class="mim-tip-reference" title="Sinkovec, M., Petrovic, D., Volk, M., Peterlin, B. <strong>Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly: a new type of heart-hand syndrome?</strong> Clin. Genet. 68: 155-160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996213</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00476.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996213">Sinkovec et al. (2005)</a>, <a href="#100" class="mim-tip-reference" title="Renou, L., Stora, S., Yaou, R. B., Volk, M., Sinkovec, M., Demay, L., Richard, P., Peterlin, B., Bonne, G. <strong>Heart-hand syndrome of Slovenian type: a new kind of laminopathy. (Letter)</strong> J. Med. Genet. 45: 666-671, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18611980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18611980</a>] [<a href="https://doi.org/10.1136/jmg.2008.060020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18611980">Renou et al. (2008)</a> identified a splice site mutation in the LMNA gene (<a href="#0045">150330.0045</a>) that segregated with disease and was not found in 100 healthy controls. Analysis of fibroblasts from 2 affected members of the family revealed truncated lamin A/C protein and nuclear envelope abnormalities, confirming the pathogenicity of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15996213+18611980" 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 Slovenian-type heart-hand syndrome, <a href="#142" class="mim-tip-reference" title="Zaragoza, M. V., Hakim, S. A., Hoang, V., Elliott, A. M. <strong>Heart-hand syndrome IV: a second family with LMNA-related cardiomyopathy and brachydactyly. (Letter)</strong> Clin. Genet. 91: 499-500, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27723096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27723096</a>] [<a href="https://doi.org/10.1111/cge.12870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27723096">Zaragoza et al. (2017)</a> identified heterozygosity for a missense mutation in the LMNA gene (R335W; <a href="#0058">150330.0058</a>) that segregated with the disorder in the family. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27723096" 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>Other Associations</em></strong></p><p>
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<a href="#48" class="mim-tip-reference" title="Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J., Anderson, C. M. <strong>Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.</strong> Physiol. Genomics 3: 39-44, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015599</a>] [<a href="https://doi.org/10.1152/physiolgenomics.2000.3.1.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11015599">Hegele et al. (2000)</a> identified a common single-nucleotide polymorphism (SNP) in LMNA, 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. <a href="#50" class="mim-tip-reference" title="Hegele, R. A., Huff, M. W., Young, T. K. <strong>Common genomic variation in LMNA modulates indexes of obesity in Inuit.</strong> J. Clin. Endocr. Metab. 86: 2747-2751, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397881</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397881">Hegele et al. (2001)</a> reported association of this LMNA SNP with anthropometric indices in 186 nondiabetic Canadian Inuit. They found that physical indices of obesity, such as body mass index, waist circumference, waist-to-hip circumference ratio, subscapular skinfold thickness, and subscapular-to-triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for approximately 10 to 100% of the attributable variation. The results indicated that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11397881+11015599" 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 14 of 15 families with familial partial lipodystrophy, <a href="#117" class="mim-tip-reference" title="Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M. <strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong> Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739751">Speckman et al. (2000)</a> identified mutations in exon 8 of the LMNA gene: 5 families had an R482Q mutation (<a href="#0010">150330.0010</a>); 7 families had an R482W alteration (<a href="#0011">150330.0011</a>), and 1 family had a G465D alteration (<a href="#0015">150330.0015</a>). The R482Q and R482W mutations occurred on different haplotypes, indicating that they probably had arisen more than once. One family with an atypical form of familial partial lipodystrophy had an R582H mutation (<a href="#0016">150330.0016</a>) in exon 11 of the LMNA gene, which the authors noted can affect the lamin A protein only. <a href="#117" class="mim-tip-reference" title="Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M. <strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong> Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739751">Speckman et al. (2000)</a> noted that all mutations in Dunnigan lipodystrophy affect the globular C-terminal domain of the lamin A/C protein, whereas mutations responsible for dilated cardiomyopathy and conduction-system disease are usually clustered in the rod domain of the protein (<a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al., 1999</a>). <a href="#117" class="mim-tip-reference" title="Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M. <strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong> Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739751">Speckman et al. (2000)</a> could not detect mutations in the LMNA gene in 1 FPLD family that showed linkage to 1q21-q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10580070+10739751" 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="#52" class="mim-tip-reference" title="Hegele, R. A. <strong>LMNA mutation position predicts organ system involvement in laminopathies.</strong> Clin. Genet. 68: 31-34, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952983</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00447.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15952983">Hegele (2005)</a> used hierarchical cluster analysis to assemble 16 laminopathy phenotypes into 2 classes based on organ system involvement, and then classified 91 reported causative LMNA mutations according to their position upstream or downstream of the nuclear localization signal (NLS) sequence. Contingency analysis revealed that laminopathy class and LMNA mutation position were strongly correlated (p less than 0.0001), suggesting that laminopathy phenotype and LMNA genotype are nonrandomly associated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952983" 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="#66" class="mim-tip-reference" title="Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A. <strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong> Clin. Genet. 71: 183-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250669">Lanktree et al. (2007)</a> analyzed the LMNA gene in 3 unrelated patients with FPLD2 and identified heterozygosity for 3 different missense mutations, all affecting only the lamin A isoform and each changing a conserved residue. Two of the mutations, D230N (<a href="#0042">150330.0042</a>) and R399C (<a href="#0043">150330.0043</a>), were 5-prime to the NLS, which is not typical of LMNA mutations in FPLD2. The third mutation, S573L (<a href="#0041">150330.0041</a>), had previously been identified in heterozygosity in a patient with dilated cardiomyopathy and conduction defects (CMD1A; <a href="/entry/115200">115200</a>) and in homozygosity in a patient with arthropathy, tendinous calcinosis, and progeroid features (see <a href="/entry/248370">248370</a>). None of the mutations were found in 200 controls of multiple ethnicities. Because heterozygosity for an S573L mutation can cause cardiomyopathy without lipodystrophy or lipodystrophy without cardiomyopathy, <a href="#66" class="mim-tip-reference" title="Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A. <strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong> Clin. Genet. 71: 183-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250669">Lanktree et al. (2007)</a> suggested that additional factors, genetic or environmental, may contribute to the precise tissue involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250669" 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="Gupta, P., Bilinska, Z. T., Sylvius, N., Boudreau, E., Veinot, J. P., Labib, S., Bolongo, P. M., Hamza, A., Jackson, T., Ploski, R., Walski, M., Grzybowski, J., Walczak, E., Religa, G., Fidzianska, A., Tesson, F. <strong>Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption.</strong> Basic Res. Cardiol. 105: 365-377, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20127487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20127487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20127487[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1007/s00395-010-0085-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20127487">Gupta et al. (2010)</a> analyzed the LMNA gene in heart samples from 25 unrelated CMD patients and identified 3 heterozygous missense mutations in 3 patients as well as a heterozygous deletion of exons 3 to 12 in 1 patient. The LMNA deletion and 1 of the missense mutations were associated with major cardiomyocyte nuclear envelope abnormalities, whereas the other 2 missense mutations were found in patients without specific nuclear envelope abnormalities. <a href="#46" class="mim-tip-reference" title="Gupta, P., Bilinska, Z. T., Sylvius, N., Boudreau, E., Veinot, J. P., Labib, S., Bolongo, P. M., Hamza, A., Jackson, T., Ploski, R., Walski, M., Grzybowski, J., Walczak, E., Religa, G., Fidzianska, A., Tesson, F. <strong>Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption.</strong> Basic Res. Cardiol. 105: 365-377, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20127487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20127487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20127487[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1007/s00395-010-0085-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20127487">Gupta et al. (2010)</a> stated that they did not find any evidence of a genotype/phenotype relationship between the onset and severity of CMD, the presence of nuclear abnormalities, and the presence or absence of LMNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20127487" 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="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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#0036">150330.0036</a>, <a href="#0055">150330.0055</a>, and <a href="#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 corresponding to prelamin A(del90) resulting from the skipping of all of exon 11. <a href="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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/619793">619793</a>) by <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> (see <a href="#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=15317753+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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<p><a href="#85" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T., Stewart, C. L. <strong>A progeroid syndrome in mice is caused by defects in A-type lamins.</strong> Nature 423: 298-301, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12748643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12748643</a>] [<a href="https://doi.org/10.1038/nature01631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12748643">Mounkes et al. (2003)</a> attempted to create a mouse model for autosomal dominant Emery-Dreifuss muscular dystrophy (<a href="/entry/181350">181350</a>) by introducing a L530P (<a href="#0004">150330.0004</a>) mutation in the LMNA gene. Although mice heterozygous for L530P did not show signs of muscular dystrophy and remained overtly normal up to 6 months of age, mice homozygous for the mutation showed phenotypes markedly reminiscent of symptoms observed in progeria patients. Homozygous Lmna L530P/L530P mice were indistinguishable from their littermates at birth, but by 4 to 6 days developed severe growth retardation, dying within 4 to 5 weeks. Homozygous mutant mice showed a slight waddling gait, suggesting immobility of joints. Other progeria features of these mutant mice included micrognathia and abnormal dentition--in approximately half of the mutants a gap was observed between the lower 2 incisors, which also appeared yellowed. Mutant mice also had loss of subcutaneous fat, reduced numbers of eccrine and sebaceous glands, increased collagen deposition in skin, and decreased hair follicle density. <a href="#85" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T., Stewart, C. L. <strong>A progeroid syndrome in mice is caused by defects in A-type lamins.</strong> Nature 423: 298-301, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12748643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12748643</a>] [<a href="https://doi.org/10.1038/nature01631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12748643">Mounkes et al. (2003)</a> concluded that Lmna L530P/L530P mice have significant phenotypic overlap with Hutchinson-Gilford progeria syndrome, including nuclear envelope abnormalities and decreased doublet capacity and life span of fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12748643" 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="#86" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L. <strong>Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.</strong> Hum. Molec. Genet. 14: 2167-2180, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972724</a>] [<a href="https://doi.org/10.1093/hmg/ddi221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972724">Mounkes et al. (2005)</a> generated mice expressing the human N195K (<a href="#0007">150330.0007</a>) mutation and observed characteristics consistent with CMD1A. Continuous electrocardiographic monitoring of cardiac activity demonstrated that N195K-homozygous mice died at an early age due to arrhythmia. Immunofluorescence and Western blot analysis showed that Hf1b/Sp4 (<a href="/entry/600540">600540</a>), connexin-40 (GJA5; <a href="/entry/121013">121013</a>), and connexin-43 (GJA1; <a href="/entry/121014">121014</a>) were misexpressed and/or mislocalized in N195K-homozygous mouse hearts. Desmin staining revealed a loss of organization at sarcomeres and intercalated disks. <a href="#86" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L. <strong>Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.</strong> Hum. Molec. Genet. 14: 2167-2180, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972724</a>] [<a href="https://doi.org/10.1093/hmg/ddi221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972724">Mounkes et al. (2005)</a> hypothesized that mutations within the LMNA gene may cause cardiomyopathy by disrupting the internal organization of the cardiomyocyte and/or altering the expression of transcription factors essential to normal cardiac development, aging, or function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15972724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacene, E., Fromes, Y., Toussaint, M., Mura, A.-M., Keller, D. I., Amthor, H., Isnard, R., Malissen, M., Schwartz, K., Bonne, G. <strong>Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.</strong> Hum. Molec. Genet. 14: 155-169, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15548545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15548545</a>] [<a href="https://doi.org/10.1093/hmg/ddi017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15548545">Arimura et al. (2005)</a> created a mouse model of autosomal dominant Emery-Dreifuss muscular dystrophy expressing an H222P mutation in Lmna. At adulthood, male homozygous mice displayed reduced locomotion activity with abnormal stiff walking posture, and all died by 9 months of age. They also developed dilated cardiomyopathy with hypokinesia and conduction defects. These skeletal and cardiac muscle features were also observed in the female homozygous mice, but with a later onset than in males. Histopathologic analysis of the mice revealed muscle degeneration with fibrosis associated with dislocation of heterochromatin and activation of Smad signaling in heart and skeletal muscles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15548545" 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="#130" 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. <strong>Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 103: 3250-3255, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16492728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16492728</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16492728[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0600012103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16492728">Varga et al. (2006)</a> created transgenic mice carrying the G608G (<a href="#0022">150330.0022</a>)-mutated human LMNA gene and observed the development of a dramatic defect of the large arteries, consisting of progressive medial vascular smooth muscle cell loss and replacement with proteoglycan and collagen followed by vascular remodeling with calcification and adventitial thickening. In vivo, these arterial abnormalities were reflected by a blunted initial response to the vasodilator sodium nitroprusside, consistent with impaired vascular relaxation, and attenuated blood pressure recovery after infusion. <a href="#130" 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. <strong>Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 103: 3250-3255, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16492728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16492728</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16492728[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0600012103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16492728">Varga et al. (2006)</a> noted that although G608G transgenic mice lacked the external phenotype seen in human progeria, they demonstrated a progressive vascular abnormality that closely resembled the most lethal aspect of the human phenotype. <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><a href="#36" class="mim-tip-reference" title="Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K. <strong>Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.</strong> Genes Dev. 20: 486-500, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16481476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16481476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16481476[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1364906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16481476">Frock et al. (2006)</a> found that most cultured muscle cells from Lmna knockout mice exhibited impaired differentiation kinetics and reduced differentiation potential. Similarly, knockdown of Lmna or emerin (EMD; <a href="/entry/300384">300384</a>) expression by RNA interference in normal muscle cells impaired differentiation potential and reduced expression of muscle-specific genes, Myod (<a href="/entry/159970">159970</a>) and desmin (<a href="/entry/125660">125660</a>). To determine whether impaired myogenesis was linked to reduced Myod or desmin levels, <a href="#36" class="mim-tip-reference" title="Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K. <strong>Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.</strong> Genes Dev. 20: 486-500, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16481476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16481476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16481476[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1364906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16481476">Frock et al. (2006)</a> individually expressed these proteins in Lmna-null myoblasts and found that both increased the differentiation potential of mutant myoblasts. <a href="#36" class="mim-tip-reference" title="Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K. <strong>Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.</strong> Genes Dev. 20: 486-500, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16481476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16481476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16481476[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1364906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16481476">Frock et al. (2006)</a> concluded that LMNA and emerin are required for myogenic differentiation, at least in part, through an effect on expression of critical myoblast proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16481476" 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>Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a truncated prelamin A, called progerin, which is farnesylated at its C terminus and accumulates at the nuclear envelope, causing misshapen nuclei (<a href="#141" 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. <strong>A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.</strong> J. Clin. Invest. 116: 2115-2121, 2006.[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://doi.org/10.1172/JCI28968" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16862216">Yang et al., 2006</a>). Farnesyltransferase inhibitors (FTIs) have been shown to reverse this cellular abnormality (<a href="#140" class="mim-tip-reference" title="Yang, S. H., Bergo, M. O., Toth, J. I., Qiao, X., Hu, Y., Sandoval, S., Meta, M., Bendale, P., Gelb, M. H., Young, S. G., Fong, L. G. <strong>Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.</strong> Proc. Nat. Acad. Sci. 102: 10291-10296, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16014412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16014412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16014412[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0504641102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16014412">Yang et al., 2005</a>; <a href="#121" class="mim-tip-reference" title="Toth, J. I., Yang, S. H., Qiao, X., Beigneux, A. P., Gelb, M. H., Moulson, C. L., Miner, J. H., Young, S. G., Fong, L. G. <strong>Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.</strong> Proc. Nat. Acad. Sci. 102: 12873-12878, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0505767102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16129834">Toth et al., 2005</a>; <a href="#15" class="mim-tip-reference" title="Capell, B. C., Erdos, M. R., Madigan, J. P., Fiordalisi, J. J., Varga, R., Conneely, K. N., Gordon, L. B., Der, C. J., Cox, A. D., Collins, F. S. <strong>Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 102: 12879-12884, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129833</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129833[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0506001102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16129833">Capell et al., 2005</a>; <a href="#76" class="mim-tip-reference" title="Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., Michaelis, S. <strong>Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 102: 14416-14421, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16186497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16186497</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16186497[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503712102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16186497">Mallampalli et al., 2005</a>). <a href="#141" 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. <strong>A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.</strong> J. Clin. Invest. 116: 2115-2121, 2006.[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://doi.org/10.1172/JCI28968" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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/?term=16186497+16862216+16129834+16129833+16014412" 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="#139" class="mim-tip-reference" title="Yang, S. H., Andres, D. A., Spielmann, H. P., Young, S. G., Fong, L. G. <strong>Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated.</strong> J. Clin. Invest. 118: 3291-3300, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18769635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18769635</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18769635[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI35876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18769635">Yang et al. (2008)</a> created knockin mice expressing a nonfarnesylatable form of progerin. Knockin mice developed the same disease phenotype as mice expressing farnesylated progerin, although the phenotype was milder, and embryonic fibroblasts derived from these mice contained fewer misshapen nuclei. The steady-state level of nonfarnesylated progerin, but not mRNA, was lower in cultured fibroblasts and whole tissues, suggesting that the absence of farnesylation may accelerate progerin turnover. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18769635" 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 mouse model of EDMD carrying an H222P mutation in the Lmna gene (<a href="#1" class="mim-tip-reference" title="Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacene, E., Fromes, Y., Toussaint, M., Mura, A.-M., Keller, D. I., Amthor, H., Isnard, R., Malissen, M., Schwartz, K., Bonne, G. <strong>Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.</strong> Hum. Molec. Genet. 14: 155-169, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15548545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15548545</a>] [<a href="https://doi.org/10.1093/hmg/ddi017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15548545">Arimura et al., 2005</a>), <a href="#88" class="mim-tip-reference" title="Muchir, A., Pavlidis,. P., Decostre, V., Herron, A. J., Arimura, T., Bonne, G., Worman, H. J. <strong>Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.</strong> J. Clin. Invest. 117: 1282-1293, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17446932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17446932</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17446932[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI29042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17446932">Muchir et al. (2007)</a> found that activation of MAPK (see <a href="/entry/176948">176948</a>) pathways preceded clinical signs or detectable molecular markers of cardiomyopathy. Expression of H222P-mutant Lmna in heart tissue and isolated cardiomyocytes resulted in tissue-specific activation of MAPKs and downstream target genes. The results suggested that activation of MAPK pathways plays a role in the pathogenesis of cardiac disease in EDMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17446932+15548545" 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="#89" class="mim-tip-reference" title="Muchir, A., Shan, J., Bonne, G., Lehnart, S. E., Worman, H. J. <strong>Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.</strong> Hum. Molec. Genet. 18: 241-247, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18927124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18927124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18927124[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18927124">Muchir et al. (2009)</a> demonstrated abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P knockin mice, a model of autosomal Emery-Dreifuss muscular dystrophy. Systemic treatment of Lmna H222P/H222P mice that developed cardiomyopathy with PD98059, an inhibitor of ERK activation, inhibited ERK phosphorylation and blocked the activation of downstream genes in heart. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere organization that occurred in placebo-treated mice. Histologic analysis and echocardiography demonstrated that treatment with PD98059 delayed the development of left ventricular dilatation. PD98059-treated Lmna H222P/H222P mice had normal cardiac ejection fractions assessed by echocardiography, whereas placebo-treated mice had a 30% decrease. The authors emphasized the role of ERK activation in the development of cardiomyopathy caused by LMNA mutations, and provided further proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18927124" 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="#26" class="mim-tip-reference" title="Davies, B. S. J., Barnes, R. H., II, Tu, Y., Ren, S., Andres, D. A., Spielmann, H. P., Lammerding, J., Wang, Y., Young, S. G., Fong, L. G. <strong>An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.</strong> Hum. Molec. Genet. 19: 2682-2694, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20421363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20421363</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20421363[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20421363">Davies et al. (2010)</a> created knockin mice harboring a mutant Lmna allele that yielded exclusively nonfarnesylated prelamin A. These mice had no evidence of progeria but succumbed to cardiomyopathy. Most of the nonfarnesylated prelamin A in the tissues of these mice was localized at the nuclear rim, indistinguishable from the lamin A in wildtype mice. The cardiomyopathy could not be ascribed to an absence of lamin C because mice expressing an otherwise identical knockin allele yielding only wildtype prelamin A appeared normal. The authors concluded that lamin C synthesis is dispensable in mice and that failure to convert prelamin A to mature lamin A causes cardiomyopathy in the absence of lamin C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20421363" 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="#20" class="mim-tip-reference" title="Choi, J. C., Wu, W., Muchir, A., Iwata, S., Homma, S., Worman, H. J. <strong>Dual specificity phosphatase 4 mediates cardiomyopathy caused by lamin A/C (LMNA) gene mutation.</strong> J. Biol. Chem. 287: 40513-40524, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23048029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23048029</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23048029[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M112.404541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23048029">Choi et al. (2012)</a> found that ERK activation in H222P/H222P mice specifically upregulated expression of dual-specificity phosphatase-4 (DUSP4; <a href="/entry/602747">602747</a>) in cardiac muscle, with much lower Dusp4 induction in quadriceps muscle, and no Dusp4 induction in tongue, kidney, and liver. Dusp4 overexpression in cultured C2C12 muscle cells or targeted to mouse heart resulted in activation of the Akt (see AKT1; <a href="/entry/164730">164730</a>)-Mtor (FRAP1; <a href="/entry/601231">601231</a>) metabolic signaling pathway, leading to impaired autophagy and abnormal cardiac metabolism, similar to findings in H222P/H222P mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23048029" 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="#120" class="mim-tip-reference" title="Thomasson, R., Vignier, N., Peccate, C., Mougenot, N., Noirez, P., Muchir, A. <strong>Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.</strong> Hum. Molec. Genet. 28: 2237-2244, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31220270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31220270</a>] [<a href="https://doi.org/10.1093/hmg/ddz056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31220270">Thomasson et al. (2019)</a> found that mice homozygous for the Lmna H222P mutation had depressed left ventricular function and altered body composition. The mutation decreased metabolic performance in mice and changed their physical activity. Supplementation with nicotinamide riboside (NR) in the diet partially restored the structure and function of striated muscles and improved the performance of mutant mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31220270" 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="#133" class="mim-tip-reference" title="Wang, Y., Shilagardi, K., Hsu, T., Odinammadu, K. O., Maruyama, T., Wu, W., Lin, C. S., Damoci, C. B., Spear, E. D., Shin, J. Y., Hsu, W., Michaelis, S., Worman, H. J. <strong>Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.</strong> Proc. Nat. Acad. Sci. 119: e2118695119, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35197292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35197292</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35197292[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.2118695119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35197292">Wang et al. (2022)</a> generated mice homozygous for a leu648-to-arg (L648R) mutation in Lmna, corresponding to the HGPS-causing L647R mutation in human LMNA that abolishes the prelamin A ZMPSTE24 cleavage site. Homozygous mutant mice expressed prelamin A and lamin C at roughly the same levels as wildtype, but they lacked mature lamin A. Mutant mice were viable, fertile, and grossly indistinguishable compared with wildtype, but they had unexpectedly long lifespans and low body mass and body fat. Microcomputed tomographic analysis revealed that homozygous mutant mice had cranial and mandibular defects with dental abnormalities, resembling those of Zmpste24 -/- mice and humans with HGPS mutations, but they appeared to be less severe and were not prominent until later in life. Mutant mice also exhibited decreased vertebral bone density and long bone defects, similar to Zmpste24 -/- mice, but they had normal grip strength with only rare rib fractures at old, preterminal ages. Analysis of embryonic fibroblasts from the mutant mice showed an accumulation of prelamin A and abnormal nuclear morphology, suggesting that accumulation of the farnesylated form of prelamin A was responsible for abnormal nuclear morphology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35197292" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>58 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=150330[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015564 OR RCV000041328 OR RCV000057350" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015564, RCV000041328, RCV000057350" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015564...</a>
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<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), <a href="#6" class="mim-tip-reference" title="Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K. <strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong> Nature Genet. 21: 285-288, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>] [<a href="https://doi.org/10.1038/6799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080180">Bonne et al. (1999)</a> identified a C-to-T transition in exon 1 of the LMNA gene that changed glutamine-6 (CAG) to a stop codon (TAG). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015565 OR RCV000057273 OR RCV000472112 OR RCV000500734 OR RCV001095717 OR RCV001813989 OR RCV003313922 OR RCV004639121" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015565, RCV000057273, RCV000472112, RCV000500734, RCV001095717, RCV001813989, RCV003313922, RCV004639121" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015565...</a>
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<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), <a href="#6" class="mim-tip-reference" title="Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K. <strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong> Nature Genet. 21: 285-288, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>] [<a href="https://doi.org/10.1038/6799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080180">Bonne et al. (1999)</a> demonstrated a C-to-T transition in exon 7 of the LMNA gene, resulting in an arg453-to-trp (R453W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57520892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57520892;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs57520892?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57520892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57520892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015569 OR RCV000015570 OR RCV000057327 OR RCV000700159 OR RCV001375641 OR RCV004018633" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015569, RCV000015570, RCV000057327, RCV000700159, RCV001375641, RCV004018633" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015569...</a>
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<p>In 2 families with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), <a href="#6" class="mim-tip-reference" title="Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K. <strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong> Nature Genet. 21: 285-288, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>] [<a href="https://doi.org/10.1038/6799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080180">Bonne et al. (1999)</a> found a G-to-C transversion in the LMNA gene which, resulting in an arg527-to-pro (R527P) substitution. The mutation, found in heterozygous state, was demonstrated to be de novo in both families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" 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="#124" class="mim-tip-reference" title="van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M. <strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong> Neurology 59: 620-623, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196663</a>] [<a href="https://doi.org/10.1212/wnl.59.4.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12196663">Van der Kooi et al. (2002)</a> reported a woman with limb-girdle muscle weakness, spinal rigidity, contractures, elevated creatine kinase, cardiac conduction abnormalities (atrial fibrillation), partial lipodystrophy (<a href="/entry/151660">151660</a>), and increased serum triglycerides who had the R527P mutation. <a href="#124" class="mim-tip-reference" title="van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M. <strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong> Neurology 59: 620-623, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196663</a>] [<a href="https://doi.org/10.1212/wnl.59.4.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12196663">Van der Kooi et al. (2002)</a> also reported a family with the R527P mutation in which the proband, her father, and her son all presented with varying degrees of EDMD, lipodystrophy, and cardiac conduction abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12196663" 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="#74" class="mim-tip-reference" title="Makri, S., Clarke, N. F., Richard, P., Maugenre, S., Demay, L., Bonne, G., Guicheney, P. <strong>Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy.</strong> Neuromusc. Disord. 19: 26-28, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19084400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19084400</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19084400">Makri et al. (2009)</a> reported 2 sisters with early-onset autosomal dominant muscular dystrophy most consistent with EDMD. Because the girls were born of consanguineous Algerian parents, they were at first thought to have an autosomal recessive congenital muscular dystrophy. However, genetic analysis identified a heterozygous R527P mutation in the LMNA gene in both patients that was not present in either unaffected parent. The results were consistent with germline mosaicism or a recurrent de novo event. The older sib had a difficult birth and showed congenital hypotonia, diffuse weakness, and mild initial respiratory and feeding difficulties. She sat unsupported at age 2 years and walked independently from age 4 years with frequent falls and a waddling gait. At 13 years she had a high-arched palate, moderate limb hypotonia, and weakness of the pelvic muscles. There was proximal limb wasting, moderate cervical, elbow, and ankle contractures, pes cavus, spinal rigidity, and lordosis/scoliosis. Her sister had mild hypotonia in early infancy, walked without support at 24 months, and showed proximal muscle weakness. There were mild contractures of the elbow and ankles. At age 9 years, she showed adiposity of the neck, trunk and abdomen, consistent with lipodystrophy. Brain MRI and cognition were normal in both sisters, and neither had cardiac involvement. Muscle biopsies showed a dystrophic pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19084400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60934003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60934003;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60934003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60934003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015571 OR RCV000057333" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015571, RCV000057333" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015571...</a>
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<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), <a href="#6" class="mim-tip-reference" title="Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K. <strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong> Nature Genet. 21: 285-288, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>] [<a href="https://doi.org/10.1038/6799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080180">Bonne et al. (1999)</a> detected a heterozygous T-to-C transition in the LMNA gene, resulting in a leu530-to-pro (L530P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 CARDIOMYOPATHY, DILATED, 1A</strong>
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LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
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LMNA, ARG60GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28928900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928900;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28928900?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28928900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28928900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015566 OR RCV000015567 OR RCV000057359" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015566, RCV000015567, RCV000057359" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015566...</a>
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<p><strong><em>Dilated Cardiomyopathy 1A</em></strong></p><p>
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In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> identified a 178C-G transversion in the LMNA gene, resulting in an arg60-to-gly (R60G) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" 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>Familial Partial Lipodystrophy, Type 2</em></strong></p><p>
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<a href="#124" class="mim-tip-reference" title="van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M. <strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong> Neurology 59: 620-623, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196663</a>] [<a href="https://doi.org/10.1212/wnl.59.4.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12196663">Van der Kooi et al. (2002)</a> reported a woman with partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), hypertriglyceridemia, and cardiomyopathy with conduction defects who carried the R60G mutation. The patient's mother reportedly had similar manifestations. The authors noted that lipodystrophy and cardiac abnormalities were combined manifestations of the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12196663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 CARDIOMYOPATHY, DILATED, 1A</strong>
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LMNA, LEU85ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933090 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933090;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015568 OR RCV000057381 OR RCV002453264" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015568, RCV000057381, RCV002453264" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015568...</a>
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<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> identified a 254T-G transversion in the LMNA gene, resulting in a leu85-to-arg (L85R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 CARDIOMYOPATHY, DILATED, 1A</strong>
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LMNA, ASN195LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933091 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933091;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015572 OR RCV000057425 OR RCV000211789 OR RCV000794743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015572, RCV000057425, RCV000211789, RCV000794743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015572...</a>
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<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> identified a 585C-G transversion in the LMNA gene, resulting in an asn195-to-lys (N195K) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Variant Function</em></strong></p><p>
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Using cells from the mouse model of <a href="#86" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L. <strong>Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.</strong> Hum. Molec. Genet. 14: 2167-2180, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972724</a>] [<a href="https://doi.org/10.1093/hmg/ddi221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972724">Mounkes et al. (2005)</a>, <a href="#54" class="mim-tip-reference" title="Ho, C. Y., Jaalouk, D. E., Vartiainen, M. K., Lammerding, J. <strong>Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.</strong> Nature 497: 507-511, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23644458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23644458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23644458[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23644458">Ho et al. (2013)</a> found that Lmna N195K embryonic fibroblasts and bone marrow-derived mesenchymal stem cells had impaired nuclear localization of the mechanosensitive transcription factor MKL1 (<a href="/entry/606078">606078</a>). Cardiac sections from Lmna(N195K/N195K) mice had significantly reduced fractions of cardiomyocytes with nuclear Mkl1, implicating altered Mkl1 signaling in the development of cardiomyopathy in these animals. Nuclear accumulation of Mkl1 was substantially lower in Lmna N195K cells than in wildtype cells. Altered nucleocytoplasmic shuttling of Mkl1 was caused by altered actin dynamics in Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin (<a href="/entry/300384">300384</a>) restored Mkl1 nuclear translocation and rescued actin dynamics in mutant cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23644458+15972724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CARDIOMYOPATHY, DILATED, 1A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933092 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933092;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015573 OR RCV000057428 OR RCV000211791 OR RCV003581565" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015573, RCV000057428, RCV000211791, RCV003581565" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015573...</a>
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<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> identified a 608A-G transition in the LMNA gene, resulting in a glu203-to-gly (E203G) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CARDIOMYOPATHY, DILATED, 1A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338938 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338938;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338938?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015574 OR RCV000057044 OR RCV000705473 OR RCV001189216 OR RCV003993745 OR RCV004018634 OR RCV004786264" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015574, RCV000057044, RCV000705473, RCV001189216, RCV003993745, RCV004018634, RCV004786264" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015574...</a>
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<p>In a family with autosomal dominant dilated cardiomyopathy and conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#31" class="mim-tip-reference" title="Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. <strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong> New Eng. J. Med. 341: 1715-1724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>] [<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10580070">Fatkin et al. (1999)</a> identified a 1711C-A transversion in the LMNA gene, resulting in an arg571-to-ser (R571S) substitution. In this family, the C-terminal of lamin C was selectively affected by the mutation, and the cardiac phenotype was relatively milder than that associated with mutations in the rod domain of the LMNA gene. Furthermore, there was subclinical evidence of involvement of skeletal muscle. Although affected members of this family had no skeletal muscle symptoms, some had elevated serum creatine kinase levels, including 1 asymptomatic family member with the genotype associated with the disease. The arg571-to-ser mutation affected only lamin C isoforms, whereas previously described defects causing Emery-Dreifuss muscular dystrophy (<a href="/entry/181350">181350</a>) perturbed both lamin A and lamin C isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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EMERY-DREIFUSS MUSCULAR DYSTROPHY 3, AUTOSOMAL RECESSIVE, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs11575937 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11575937;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs11575937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs11575937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015575 OR RCV000041318 OR RCV000057299 OR RCV000190399 OR RCV000459624 OR RCV000754814 OR RCV000763258 OR RCV001179839 OR RCV001822996 OR RCV002390111 OR RCV004532361 OR RCV004806012" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015575, RCV000041318, RCV000057299, RCV000190399, RCV000459624, RCV000754814, RCV000763258, RCV001179839, RCV001822996, RCV002390111, RCV004532361, RCV004806012" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015575...</a>
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<p>In 5 probands from 5 Canadian kindreds with familial partial lipodystrophy of the Dunnigan type (FPLD2; <a href="/entry/151660">151660</a>), <a href="#11" class="mim-tip-reference" title="Cao, H., Hegele, R. A. <strong>Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 9: 109-112, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587585</a>] [<a href="https://doi.org/10.1093/hmg/9.1.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10587585">Cao and Hegele (2000)</a> demonstrated heterozygosity for a G-to-A transition in exon 8 of the LMNA gene, predicted to result in an arg484-to-gln (R482Q) substitution. There were no differences in age, gender, or body mass index in Q482/R482 heterozygotes compared with R482/R482 homozygotes (normals) from these families; however, there were significantly more Q482/R482 heterozygotes who had definite partial lipodystrophy and frank diabetes. Also compared with the normal homozygotes, heterozygotes had significantly higher serum insulin and C-peptide (see <a href="/entry/176730">176730</a>) levels. The LMNA heterozygotes with diabetes were significantly older than heterozygotes without diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587585" 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="#110" class="mim-tip-reference" title="Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C. <strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong> Nature Genet. 24: 153-156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655060</a>] [<a href="https://doi.org/10.1038/72807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655060">Shackleton et al. (2000)</a> found the R482Q mutation in a family with familial partial lipodystrophy. <a href="#49" class="mim-tip-reference" title="Hegele, R. A., Cao, H., Huff, M. W., Anderson, C. M. <strong>LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.</strong> J. Clin. Endocr. Metab. 85: 3089-3093, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999791</a>] [<a href="https://doi.org/10.1210/jcem.85.9.6768" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10999791">Hegele et al. (2000)</a> analyzed the relationship between plasma leptin (<a href="/entry/164160">164160</a>) and the rare LMNA R482Q mutation in 23 adult familial partial lipodystrophy (FPLD) subjects compared with 25 adult family controls with normal LMNA in an extended Canadian FPLD kindred. They found that the LMNA Q482/R482 genotype was a significant determinant of plasma leptin, the ratio of plasma leptin to body mass index (BMI), plasma insulin, and plasma C peptide, but not BMI. Family members who were Q482/R482 heterozygotes had significantly lower plasma leptin and leptin:BMI ratio than unaffected R482/R482 homozygotes. Fasting plasma concentrations of insulin and C peptide were both significantly higher in LMNA Q482/R482 heterozygotes than in R482/R482 homozygotes. Multivariate regression analysis revealed that the LMNA R482Q genotype accounted for 40.9%, 48.2%, 86.9%, and 81.0%, respectively, of the attributable variation in log leptin, leptin:BMI ratio, log insulin, and log C peptide. The authors concluded that a rare FPLD mutation in LMNA determines the plasma leptin concentration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10655060+10999791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Boguslavsky, R. L., Stewart, C. L., Worman, H. J. <strong>Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 15: 653-663, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415042</a>] [<a href="https://doi.org/10.1093/hmg/ddi480" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415042">Boguslavsky et al. (2006)</a> found that overexpression of wildtype LMNA or mutant R482Q or R482W (<a href="#0011">150330.0011</a>) in mouse 3T3-L1 preadipocytes prevented cellular lipid accumulation, inhibited triglyceride synthesis, and prevented normal differentiation into adipocytes. In contrast, embryonic fibroblasts from Lmna-null mice had increased levels of basal triglyceride synthesis and differentiated into fat-containing cells more readily that wildtype mouse cells. Mutations at residue 482 are not predicted to affect the structure of the nuclear lamina, but may change interactions with other proteins. The findings of this study suggested that mutations responsible for FPLD are gain-of-function mutations. <a href="#5" class="mim-tip-reference" title="Boguslavsky, R. L., Stewart, C. L., Worman, H. J. <strong>Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 15: 653-663, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415042</a>] [<a href="https://doi.org/10.1093/hmg/ddi480" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415042">Boguslavsky et al. (2006)</a> postulated that mutations that result in gain of function may cause higher binding affinity to a proadipogenic transcription factor, thus preventing it from activating target genes; overexpression of the wildtype protein may result in increased numbers of molecules with a normal binding affinity. Overexpression of Lmna was associated with decreased levels of PPARG2 (<a href="/entry/601487">601487</a>), a nuclear hormone receptor transcription factor putatively involved in adipogenic conversion. Lmna-null cells had increased basal phosphorylation of AKT1 (<a href="/entry/164730">164730</a>), a mediator of insulin signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415042" 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 Hutterite family with FPLD2, <a href="#135" class="mim-tip-reference" title="Wiltshire, K. M., Hegele, R. A., Innes, A. M., Brownell, A. K. W. <strong>Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.</strong> Neuromusc. Disord. 23: 265-268, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23313286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23313286</a>] [<a href="https://doi.org/10.1016/j.nmd.2012.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23313286">Wiltshire et al. (2013)</a> identified a heterozygous R482Q mutation. Two family members were homozygous for the mutation and presented with onset of autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; <a href="/entry/616516">616516</a>) as well as partial lipodystrophy in the first or second decades. The findings expanded the phenotype associated with this mutation. The overall frequency of the mutation in Dariusleut and Lehrerleut Hutterites in Alberta, Canada, was found to be 1.45%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23313286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57920071 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57920071;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs57920071?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57920071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57920071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015579 OR RCV000057298 OR RCV001174239 OR RCV001235764 OR RCV001248961 OR RCV002390112 OR RCV002482872 OR RCV004532362" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015579, RCV000057298, RCV001174239, RCV001235764, RCV001248961, RCV002390112, RCV002482872, RCV004532362" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015579...</a>
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<p>In 6 families and 3 isolated cases of partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#110" class="mim-tip-reference" title="Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C. <strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong> Nature Genet. 24: 153-156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655060</a>] [<a href="https://doi.org/10.1038/72807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655060">Shackleton et al. (2000)</a> found heterozygosity for C-to-T transition in the LMNA gene, resulting in an arg482-to-trp (R482W) substitution. This is the same codon as that affected in the R482Q mutation (<a href="#0010">150330.0010</a>). R482L (<a href="#0012">150330.0012</a>) is a third mutation in the same codon causing partial lipodystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655060" 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="#107" class="mim-tip-reference" title="Schmidt, H. H.-J., Genschel, J., Baier, P., Schmidt, M., Ockenga, J., Tietge, U. J. F., Propsting, M., Buttner, C., Manns, M. P., Lochs, H., Brabant, G. <strong>Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.</strong> J. Clin. Endocr. Metab. 86: 2289-2295, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11344241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11344241</a>] [<a href="https://doi.org/10.1210/jcem.86.5.7500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11344241">Schmidt et al. (2001)</a> identified a family with partial lipodystrophy carrying the R482W mutation in the LMNA gene. Clinically, the loss of subcutaneous fat and muscular hypertrophy, especially of the lower extremities, started as early as in childhood. Acanthosis and severe hypertriglyceridemia developed later in life, followed by diabetes. Characterization of the lipoprotein subfractions revealed that affected children present with hyperlipidemia. The presence and severity of hyperlipidemia seem to be influenced by age, apolipoprotein E genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipidemia is an early and prominent feature in the presented lipodystrophic family carrying the R482W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11344241" 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="#122" class="mim-tip-reference" title="Vadrot, N., Duband-Goulet, I., Cabet, E., Attanda, W., Barateau, A., Vicart, P., Gerbal, F., Briand, N., Vigouroux, C., Oldenburg, A. R., Lund, E. G., Collas, P., Buendia, B. <strong>The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 24: 2096-2109, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25524705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25524705</a>] [<a href="https://doi.org/10.1093/hmg/ddu728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25524705">Vadrot et al. (2015)</a> stated that R482 is located within the Ig fold common to A-type lamins, and found that the Ig fold is involved in binding of A-type lamins to SREBP1. In overexpression studies in primary human preadipocytes and patient fibroblasts, <a href="#122" class="mim-tip-reference" title="Vadrot, N., Duband-Goulet, I., Cabet, E., Attanda, W., Barateau, A., Vicart, P., Gerbal, F., Briand, N., Vigouroux, C., Oldenburg, A. R., Lund, E. G., Collas, P., Buendia, B. <strong>The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.</strong> Hum. Molec. Genet. 24: 2096-2109, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25524705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25524705</a>] [<a href="https://doi.org/10.1093/hmg/ddu728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25524705">Vadrot et al. (2015)</a> found that the R482W substitution reduced the inhibitory interaction of mutant LMNA with SREBP1. R482W patient fibroblasts showed elevated SREBP1 transcriptional activity and derepression of a large number of SREBP1 target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25524705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs11575937 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11575937;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs11575937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs11575937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a family with partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#110" class="mim-tip-reference" title="Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C. <strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong> Nature Genet. 24: 153-156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655060</a>] [<a href="https://doi.org/10.1038/72807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655060">Shackleton et al. (2000)</a> found that the affected individuals were heterozygous for a G-to-T transversion in the LMNA gene, resulting in an arg482-to-leu (R482L) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015581 OR RCV000057492 OR RCV000681609" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015581, RCV000057492, RCV000681609" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015581...</a>
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<p>In a large family with a severe autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>) in which the majority of affected family members showed signs of mild skeletal muscle involvement, <a href="#7" class="mim-tip-reference" title="Brodsky, G. L., Muntoni, F., Miocic, S., Sinagra, G., Sewry, C., Mestroni, L. <strong>Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement.</strong> Circulation 101: 473-476, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10662742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10662742</a>] [<a href="https://doi.org/10.1161/01.cir.101.5.473" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10662742">Brodsky et al. (2000)</a> demonstrated heterozygosity in affected members for a 1-bp deletion (del959T) deletion in exon 6 of the LMNA gene. One individual had a pattern of skeletal muscle involvement that the authors considered consistent with mild Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10662742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28928901 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928901;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28928901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28928901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015583 OR RCV000057440 OR RCV004577319" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015583, RCV000057440, RCV004577319" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015583...</a>
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<p>In a 40-year-old man with autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; <a href="/entry/616516">616516</a>), <a href="#97" class="mim-tip-reference" title="Raffaele di Barletta, M., Ricci, E., Galluzzi, G., Tonali, P., Mora, M., Morandi, L., Romorini, A., Voit, T., Orstavik, K. H., Merlini, L., Trevisan, C., Biancalana, V., Housmanowa-Petrusewicz, I., Bione, S., Ricotti, R., Schwartz, K., Bonne, G., Toniolo, D. <strong>Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 66: 1407-1412, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739764">Raffaele di Barletta et al. (2000)</a> found a homozygous 664C-T transition in the LMNA gene, resulting in a his222-to-tyr (H222Y) amino acid substitution. Both parents, who were first cousins, were heterozygous for the mutation and were unaffected. The mutation was not found among 200 control chromosomes. The patient was the only one with a homozygous LMNA mutation among a larger study of individuals with autosomal dominant Emery-Dreifuss muscular dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10739764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61282106 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61282106;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61282106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs61282106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015584 OR RCV000057287 OR RCV001851878" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015584, RCV000057287, RCV001851878" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015584...</a>
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<p><a href="#117" class="mim-tip-reference" title="Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M. <strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong> Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739751">Speckman et al. (2000)</a> found that 1 of 15 families with familial partial lipodystrophy of the Dunnigan variety (FPLD2; <a href="/entry/151660">151660</a>) harbored a gly465-to-asp (G465D) mutation in exon 8 of the LMNA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10739751" 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="#114" class="mim-tip-reference" title="Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L. <strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong> Molec. Biol. Cell 24: 342-350, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23243001">Simon et al. (2013)</a> noted that G465 is located at the 'bottom front' of the Ig-fold of the mature lamin A tail. They found that the G465D substitution reduced SUMO1 (<a href="/entry/601912">601912</a>), but not SUMO2 (<a href="/entry/603042">603042</a>), modification of the lamin A tail in vitro and in cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23243001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57830985 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57830985;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs57830985?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57830985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57830985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015585 OR RCV000057353 OR RCV001068657 OR RCV001804734 OR RCV002399327 OR RCV003996099 OR RCV004532363 OR RCV004795416" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015585, RCV000057353, RCV001068657, RCV001804734, RCV002399327, RCV003996099, RCV004532363, RCV004795416" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015585...</a>
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<p>In a family with an atypical form of familial partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#117" class="mim-tip-reference" title="Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M. <strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong> Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10739751">Speckman et al. (2000)</a> identified an arg582-to-his (R582H) mutation in exon 11 of the LMNA gene. In a follow-up of this same family, <a href="#39" class="mim-tip-reference" title="Garg, A., Vinaitheerthan, M., Weatherall, P. T., Bowcock, A. M. <strong>Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene.</strong> J. Clin. Endocr. Metab. 86: 59-65, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231979</a>] [<a href="https://doi.org/10.1210/jcem.86.1.7121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11231979">Garg et al. (2001)</a> reported that 2 affected sisters showed less severe loss of subcutaneous fat from the trunk and extremities with some retention of fat in the gluteal region and medial parts of the proximal thighs compared to women with typical FPLD2. Noting that the R582H mutation interrupts only the lamin A protein, <a href="#39" class="mim-tip-reference" title="Garg, A., Vinaitheerthan, M., Weatherall, P. T., Bowcock, A. M. <strong>Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene.</strong> J. Clin. Endocr. Metab. 86: 59-65, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231979</a>] [<a href="https://doi.org/10.1210/jcem.86.1.7121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11231979">Garg et al. (2001)</a> suggested that in typical FPLD2, interruption of both lamins A and C causes a more severe phenotype than that seen in atypical FPLD2, in which only lamin A is altered. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10739751+11231979" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0017 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs61672878 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61672878;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs61672878?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61672878" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs61672878" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000057235 OR RCV000503996 OR RCV000547164 OR RCV000681569 OR RCV001089610 OR RCV002321484 OR RCV003319170 OR RCV005042056" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000057235, RCV000503996, RCV000547164, RCV000681569, RCV001089610, RCV002321484, RCV003319170, RCV005042056" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000057235...</a>
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<p>In a family (family C) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; <a href="/entry/181350">181350</a>) by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#87" class="mim-tip-reference" title="Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K. <strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong> Hum. Molec. Genet. 9: 1453-1459, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814726</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814726">Muchir et al. (2000)</a> found a G-to-A transition in exon 6 of the LMNA gene, resulting in a substitution of histidine for arginine-377 (R377H). This family was previously reported by van der Kooi et al. (<a href="#125" class="mim-tip-reference" title="van der Kooi, A. J., Ledderhof, T. M., de Voogt, W. G., Res, J. C. J., Bouwsma, G., Troost, D., Busch, H. F. M., Becker, A. E., de Visser, M. <strong>A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement.</strong> Ann. Neurol. 39: 636-642, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619549</a>] [<a href="https://doi.org/10.1002/ana.410390513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8619549">1996</a>, <a href="#126" class="mim-tip-reference" title="van der Kooi, A. J., van Meegen, M., Ledderhof, T. M., McNally, E. M., de Visser, M., Bolhuis, P. A. <strong>Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21.</strong> Am. J. Hum. Genet. 60: 891-895, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106535</a>]" pmid="9106535">1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+10814726+8619549+9106535" 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="#119" class="mim-tip-reference" title="Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group. <strong>Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.</strong> J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12628721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12628721</a>] [<a href="https://doi.org/10.1016/s0735-1097(02)02954-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12628721">Taylor et al. (2003)</a> identified heterozygosity for the R377H mutation in an American family of British descent with autosomal dominant dilated cardiomyopathy and mild limb-girdle muscular disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12628721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M. <strong>Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.</strong> Hum. Mutat. 21: 473-481, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673789</a>] [<a href="https://doi.org/10.1002/humu.10170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673789">Charniot et al. (2003)</a> described a French family with autosomal dominant severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias and a skeletal muscular dystrophy of the quadriceps muscles. Affected members were found to carry the R377H mutation, which was shown by transfection experiments in both muscular and nonmuscular cells to lead to mislocalization of both lamin and emerin (<a href="/entry/300384">300384</a>). Unlike previously reported cases of LMNA mutations causing dilated cardiomyopathy with neuromuscular involvement, cardiac involvement preceded neuromuscular disease in all affected members. <a href="#17" class="mim-tip-reference" title="Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M. <strong>Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.</strong> Hum. Mutat. 21: 473-481, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673789</a>] [<a href="https://doi.org/10.1002/humu.10170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673789">Charniot et al. (2003)</a> suggested that factors other than the R377H mutation influenced phenotypic expression in this family. <a href="#109" class="mim-tip-reference" title="Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. <strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong> J. Med. Genet. 40: 560-567, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>] [<a href="https://doi.org/10.1136/jmg.40.8.560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920062">Sebillon et al. (2003)</a> also reported on this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12673789+12920062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a German woman who had been diagnosed with LGMD1B, <a href="#102" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Botzenhart, E., Eggermann, T., Senderek, J., Schoser, B. G. H., Schroder, R., Wehnert, M., Wirth, B., Zerres, K. <strong>Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.</strong> Neurogenetics 8: 137-142, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17136397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17136397</a>] [<a href="https://doi.org/10.1007/s10048-006-0070-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17136397">Rudnik-Schoneborn et al. (2007)</a> identified a heterozygous R377H mutation in the LMNA gene. Family history revealed that the patient's paternal grandmother had proximal muscle weakness and died from heart disease at age 52, and a paternal aunt had 'walking difficulties' since youth. The patient's father and 4 cousins all had cardiac disease without muscle weakness ranging from nonspecific 'heart attacks' to dilated cardiomyopathy and arrhythmia. The only living affected cousin also carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17136397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607540 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607540;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267607540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a family (family A) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; <a href="/entry/181350">181350</a>) by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#87" class="mim-tip-reference" title="Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K. <strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong> Hum. Molec. Genet. 9: 1453-1459, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814726</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814726">Muchir et al. (2000)</a> found a 3-bp deletion (AAG) in exon 3 of the LMNA gene, resulting in loss of the codon for lysine-208 (delK208). This family was previously reported by van der Kooi et al. (<a href="#125" class="mim-tip-reference" title="van der Kooi, A. J., Ledderhof, T. M., de Voogt, W. G., Res, J. C. J., Bouwsma, G., Troost, D., Busch, H. F. M., Becker, A. E., de Visser, M. <strong>A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement.</strong> Ann. Neurol. 39: 636-642, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619549</a>] [<a href="https://doi.org/10.1002/ana.410390513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8619549">1996</a>, <a href="#126" class="mim-tip-reference" title="van der Kooi, A. J., van Meegen, M., Ledderhof, T. M., McNally, E. M., de Visser, M., Bolhuis, P. A. <strong>Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21.</strong> Am. J. Hum. Genet. 60: 891-895, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106535</a>]" pmid="9106535">1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+10814726+8619549+9106535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607539 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607539;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267607539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015589 OR RCV000057336 OR RCV002390205" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015589, RCV000057336, RCV002390205" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015589...</a>
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<p>In a family (family B) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; <a href="/entry/181350">181350</a>) by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#87" class="mim-tip-reference" title="Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K. <strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong> Hum. Molec. Genet. 9: 1453-1459, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814726</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814726">Muchir et al. (2000)</a> found a G-to-C transversion in the splice donor site of intron 9, leading to retention of intron 9 and a frameshift at position 536. This potentially results in a truncated protein lacking half of the globular tail domain of lamins A/C. This family was previously reported by van der Kooi et al. (<a href="#125" class="mim-tip-reference" title="van der Kooi, A. J., Ledderhof, T. M., de Voogt, W. G., Res, J. C. J., Bouwsma, G., Troost, D., Busch, H. F. M., Becker, A. E., de Visser, M. <strong>A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement.</strong> Ann. Neurol. 39: 636-642, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619549</a>] [<a href="https://doi.org/10.1002/ana.410390513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8619549">1996</a>, <a href="#126" class="mim-tip-reference" title="van der Kooi, A. J., van Meegen, M., Ledderhof, T. M., McNally, E. M., de Visser, M., Bolhuis, P. A. <strong>Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21.</strong> Am. J. Hum. Genet. 60: 891-895, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106535</a>]" pmid="9106535">1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+10814726+8619549+9106535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015590 OR RCV000057479 OR RCV000653885 OR RCV000826146 OR RCV000986429 OR RCV001176301 OR RCV002467495 OR RCV003162253 OR RCV003996100 OR RCV005042057" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015590, RCV000057479, RCV000653885, RCV000826146, RCV000986429, RCV001176301, RCV002467495, RCV003162253, RCV003996100, RCV005042057" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015590...</a>
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<p><a href="#28" class="mim-tip-reference" title="De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N. <strong>Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.</strong> Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799477</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11799477[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799477">De Sandre-Giovannoli et al. (2002)</a> found a homozygous arg298-to-cys (R298C) mutation in the LMNA gene in affected members of Algerian families with axonal Charcot-Marie-Tooth disease type 2B1 (CMT2B1; <a href="/entry/605588">605588</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799477" 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="Ben Yaou, R., Toutain, A., Arimura, T., Demay, L., Massart, C., Peccate, C., Muchir, A., Llense, S., Deburgreave, N., Leturcq, F., Litim, K. E., Rahmoun-Chiali, N., Richard, P., Babuty, D., Recan-Budiartha, D., Bonne, G. <strong>Multitissular involvement in a family with LMNA and EMD mutations: role of digenic mechanism?</strong> Neurology 68: 1883-1894, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17536044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17536044</a>] [<a href="https://doi.org/10.1212/01.wnl.0000263138.57257.6a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17536044">Ben Yaou et al. (2007)</a> identified a homozygous R298C mutation in a female and 2 male affected members of an Algerian family with CMT2B1. The 2 males also had X-linked Emery-Dreifuss muscular dystrophy (<a href="/entry/310300">310300</a>) and a hemizygous mutation in the EMD gene (<a href="/entry/300384">300384</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17536044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0021 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57520892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57520892;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs57520892?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57520892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57520892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015591 OR RCV000015592 OR RCV000057326 OR RCV000148607 OR RCV000555364 OR RCV001174240 OR RCV001178367 OR RCV002399328 OR RCV003996101 OR RCV005042058" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015591, RCV000015592, RCV000057326, RCV000148607, RCV000555364, RCV001174240, RCV001178367, RCV002399328, RCV003996101, RCV005042058" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015591...</a>
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<p>In 5 consanguineous Italian families, <a href="#93" class="mim-tip-reference" title="Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M. R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G. <strong>Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.</strong> Am. J. Hum. Genet. 71: 426-431, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075506</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12075506[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/341908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075506">Novelli et al. (2002)</a> demonstrated that individuals with mandibuloacral dysplasia (MADA; <a href="/entry/248370">248370</a>) were homozygous for an arg527-to-his (R527H) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075506" 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 from 2 pedigrees with MADA, <a href="#113" class="mim-tip-reference" title="Simha, V., Agarwal, A. K., Oral, E. A., Fryns, J.-P., Garg, A. <strong>Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.</strong> J. Clin. Endocr. Metab. 88: 2821-2824, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788894</a>] [<a href="https://doi.org/10.1210/jc.2002-021575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12788894">Simha et al. (2003)</a> identified the homozygous R527H mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788894" 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 Mexican American boy with MADA born of related parents, <a href="#111" class="mim-tip-reference" title="Shen, J. J., Brown, C. A., Lupski, J. R., Potocki, L. <strong>Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C.</strong> J. Med. Genet. 40: 854-857, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627682</a>] [<a href="https://doi.org/10.1136/jmg.40.11.854" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14627682">Shen et al. (2003)</a> identified homozygosity for the R527H mutation. The authors noted that all the patients reported by <a href="#93" class="mim-tip-reference" title="Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M. R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G. <strong>Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.</strong> Am. J. Hum. Genet. 71: 426-431, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075506</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12075506[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/341908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075506">Novelli et al. (2002)</a> shared a common disease haplotype, but that the patients reported by <a href="#113" class="mim-tip-reference" title="Simha, V., Agarwal, A. K., Oral, E. A., Fryns, J.-P., Garg, A. <strong>Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.</strong> J. Clin. Endocr. Metab. 88: 2821-2824, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788894</a>] [<a href="https://doi.org/10.1210/jc.2002-021575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12788894">Simha et al. (2003)</a> and their Mexican American patient had different haplotypes, indicating independent origins of the mutation. The mutation is located within the C-terminal immunoglobulin-like domain in the center of a beta sheet on the domain surface of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12075506+14627682+12788894" 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="#72" class="mim-tip-reference" title="Lombardi, F., Gullotta, F., Columbaro, M., Filareto, A., D'Adamo, M., Vielle, A., Guglielmi, V., Nardone, A. M., Azzolini, V., Grosso, E., Lattanzi, G., D'Apice, M. R., Masala, S., Maraldi, N. M., Sbraccia, P., Novelli, G. <strong>Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.</strong> J. Clin. Endocr. Metab. 92: 4467-4471, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17848409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17848409</a>] [<a href="https://doi.org/10.1210/jc.2007-0116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17848409">Lombardi et al. (2007)</a> identified this mutation in compound heterozygosity with another missense mutation (V440M; <a href="#0044">150330.0044</a>) in a patient with an apparent MADA phenotype associated with muscular hyposthenia and generalized hypotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17848409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Garavelli, L., D'Apice, M. R., Rivieri, F., Bertoli, M., Wischmeijer, A., Gelmini, C., De Nigris, V., Albertini, E., Rosato, S., Virdis, R., Bacchini, E., Dal Zotto, R., Banchini, G., Iughetti, L., Bernasconi, S., Superti-Furga, A., Novelli, G. <strong>Mandibuloacral dysplasia type A in childhood.</strong> Am. J. Med. Genet. 149A: 2258-2264, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19764019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19764019</a>] [<a href="https://doi.org/10.1002/ajmg.a.33005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19764019">Garavelli et al. (2009)</a> reported 2 unrelated patients with early childhood onset of MADA features associated with a homozygous R527H mutation. One presented at age 5 years, 3 months with bulbous distal phalanges of fingers and was observed to have dysmorphic craniofacial features, lipodystrophy type A, and acroosteolysis. The second child, born of consanguineous Pakistani parents, presented at age 4 years, 2 months with a round face, chubby cheeks, thin nose, lipodystrophy type A, and short, broad distal phalanges. <a href="#37" class="mim-tip-reference" title="Garavelli, L., D'Apice, M. R., Rivieri, F., Bertoli, M., Wischmeijer, A., Gelmini, C., De Nigris, V., Albertini, E., Rosato, S., Virdis, R., Bacchini, E., Dal Zotto, R., Banchini, G., Iughetti, L., Bernasconi, S., Superti-Furga, A., Novelli, G. <strong>Mandibuloacral dysplasia type A in childhood.</strong> Am. J. Med. Genet. 149A: 2258-2264, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19764019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19764019</a>] [<a href="https://doi.org/10.1002/ajmg.a.33005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19764019">Garavelli et al. (2009)</a> emphasized that features of this disorder may become apparent as early as preschool age and that bulbous fingertips may be a clue to the diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs58596362 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58596362;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs58596362?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs58596362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs58596362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015593 OR RCV000057364 OR RCV000150957 OR RCV000806737 OR RCV001847608" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015593, RCV000057364, RCV000150957, RCV000806737, RCV001847608" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015593...</a>
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<p><strong><em>Hutchinson-Gilford Progeria Syndrome</em></strong></p><p>
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In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> found an identical de novo 1824C-T transition, resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and results in activation of a cryptic splice site and deletion of 50 codons of prelamin A. This mutation was not identified in any of the 16 parents available for testing. <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="#27" 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. <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://doi.org/10.1126/science.1084125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702809">De Sandre-Giovannoli et al. (2003)</a> identified the exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del) 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><a href="#12" class="mim-tip-reference" title="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://doi.org/10.1007/s10038-003-0025-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12768443">Cao and Hegele (2003)</a> confirmed the observations of <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> using the same cell lines. They referred to this mutation as 2036C-T. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12768443+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="#25" class="mim-tip-reference" title="D'Apice, M. R., Tenconi, R., Mammi, I., van den Ende, J., Novelli, G. <strong>Paternal origin of LMNA mutations in Hutchinson-Gilford progeria. (Letter)</strong> Clin. Genet. 65: 52-54, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15032975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15032975</a>] [<a href="https://doi.org/10.1111/j..2004.00181.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15032975">D'Apice et al. (2004)</a> confirmed paternal age effect and demonstrated a paternal origin of the 2036C-T mutation in 3 families with isolated cases of Hutchinson-Gilford progeria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15032975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By light and electron microscopy of fibroblasts from HGPS patients carrying the 1824C-T mutation, <a href="#43" 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. <strong>Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184648</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0402943101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#43" 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. <strong>Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184648</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0402943101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15184648">Goldman et al. (2004)</a> designated LA delta-50. Introduction of LA delta-50 into normal cells by transfection or protein injection induced the same changes. <a href="#43" 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. <strong>Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.</strong> Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184648</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0402943101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15184648">Goldman et al. (2004)</a> hypothesized that the alterations in nuclear structure are due to a concentration-dependent dominant-negative effect of LA delta-50, leading to the disruption of lamin-related functions ranging from the maintenance of nuclear shape to regulation of gene expression and DNA replication. <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>In a patient with Hutchinson-Gilford progeria, <a href="#137" class="mim-tip-reference" title="Wuyts, W., Biervliet, M., Reyniers, E., D'Apice, M. R., Novelli, G., Storm, K. <strong>Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.</strong> Am. J. Med. Genet. 135A: 66-68, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15793835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15793835</a>] [<a href="https://doi.org/10.1002/ajmg.a.30663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15793835">Wuyts et al. (2005)</a> identified the G608G mutation. 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 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><a href="#42" class="mim-tip-reference" title="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> Hum. Molec. Genet. 14: 2959-2969, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16126733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16126733</a>] [<a href="https://doi.org/10.1093/hmg/ddi326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16126733">Glynn and Glover (2005)</a> studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and G608G-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="#42" class="mim-tip-reference" title="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> Hum. Molec. Genet. 14: 2959-2969, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16126733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16126733</a>] [<a href="https://doi.org/10.1093/hmg/ddi326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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>In cells from a female patient with HGPS due to the 1824C-T mutation, <a href="#112" class="mim-tip-reference" title="Shumaker, D. K., Dechat, T., Kohlmaier, A., Adam, S. A., Bozovsky, M. R., Erdos, M. R., Eriksson, M., Goldman, A. E., Khuon, S., Collins, F. S., Jenuwein, T., Goldman, R. D. <strong>Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging.</strong> Proc. Nat. Acad. Sci. 103: 8703-8708, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738054</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16738054[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602569103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16738054">Shumaker et al. (2006)</a> found that the inactive X chromosome showed loss of histone H3 trimethylation of lys27 (H3K27me3), a marker for facultative heterochromatin, as well as loss of histone H3 trimethylation of lys9 (H3K9me3), a marker of pericentric constitutive heterochromatin. Other alterations in epigenetic control included downregulation of the EZH2 methyltransferase (<a href="/entry/601573">601573</a>), upregulation of pericentric satellite III repeat transcripts, and increase in the trimethylation of H4K20. The epigenetic alterations were observed before the pathogenic changes in nuclear shape. The findings indicated that the mutant LMNA protein alters sites of histone methylation known to regulate heterochromatin and provided evidence that the rapid aging phenotype of HGPS reflects aspects of normal aging at the molecular level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16738054" 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="#84" 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. <strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong> Hum. Mutat. 28: 882-889, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>] [<a href="https://doi.org/10.1002/humu.20536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17469202">Moulson et al. (2007)</a> demonstrated that HGPS cells with the common 1824C-T LMNA mutation produced about 37.5% of wildtype full-length transcript, which was higher than previous estimates (<a href="#99" class="mim-tip-reference" title="Reddel, C. J., Weiss, A. S. <strong>Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 715-717, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342704</a>] [<a href="https://doi.org/10.1136/jmg.2004.019323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342704">Reddel and Weiss, 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15342704+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>Using real-time RT-PCR, <a href="#101" class="mim-tip-reference" title="Rodriguez, S., Coppede, F., Sagelius, H., Eriksson, M. <strong>Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging.</strong> Europ. J. Hum. Genet. 17: 928-937, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19172989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19172989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19172989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19172989">Rodriguez et al. (2009)</a> found that progerin transcripts were expressed in dermal fibroblasts cultured from normal controls, but at a level more than 160-fold lower than that detected in dermal fibroblasts cultured from HGPS patients. The level of progerin transcripts, but not of lamin A or lamin C transcripts, increased in late-passage cells from both normal controls and HGPS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19172989" 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>Restrictive Dermopathy 2</em></strong></p><p>
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In an infant (P2) with restrictive dermopathy (RSDM2; <a href="/entry/619793">619793</a>), <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> identified the 1824C-T transition in the LMNA gene in heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=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>
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<strong>.0023 HUTCHINSON-GILFORD PROGERIA SYNDROME</strong>
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LMNA, GLY608SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs61064130 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61064130;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs61064130?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61064130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs61064130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015595 OR RCV000057363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015595, RCV000057363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015595...</a>
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<p>In a patient with Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> identified a G-to-A transition in the LMNA gene resulting in a gly-to-ser substitution at codon 608 (G608S). This mutation was not identified in either parent. <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="#12" class="mim-tip-reference" title="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://doi.org/10.1007/s10038-003-0025-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12768443">Cao and Hegele (2003)</a> confirmed the observation of <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> using the same cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12768443+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>
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<strong>.0024 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60310264 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60310264;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60310264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60310264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015596 OR RCV000057406 OR RCV000192009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015596, RCV000057406, RCV000192009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015596...</a>
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<p>In a patient with somewhat atypical features of Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#30" 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. <strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong> Nature 423: 293-298, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>] [<a href="https://doi.org/10.1038/nature01629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12714972">Eriksson et al. (2003)</a> identified a glu-to-lys substitution at codon 145 (E145K) in exon 2 of the LMNA gene. This mutation was not identified in either parent. Atypical clinical features, including persistence of coarse hair over the head, ample subcutaneous tissue over the arms and legs, and severe strokes beginning at age 4, may subtly distinguish this phenotype from classic HGPS. <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>
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<strong>.0025 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28928902 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928902;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28928902?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28928902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28928902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015597 OR RCV000057293 OR RCV001246687" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015597, RCV000057293, RCV001246687" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015597...</a>
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<p>In a patient with an apparently typical progeria phenotype (<a href="/entry/176670">176670</a>) who was 28 years old at the time that DNA was obtained, <a href="#12" class="mim-tip-reference" title="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://doi.org/10.1007/s10038-003-0025-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12768443">Cao and Hegele (2003)</a> identified compound heterozygosity for 2 missense mutations in the LMNA gene. One mutation, arg471 to cys (R471C), resulted from a 1623C-T transition. An arg527-to-cys (R527C) substitution (<a href="#0026">150330.0026</a>), resulting from a 1791C-T transition, was found on the other allele. These mutations were not identified in any of 100 control chromosomes. Parental DNA for this patient and a clinical description of the parents were not available. <a href="#10" class="mim-tip-reference" title="Brown, W. T. <strong>Personal Communication.</strong> Staten Island, N.Y. 1/12/2004."None>Brown (2004)</a> reported that both he and the patient's physician, Francis Collins, concluded that the patient had mandibuloacral dysplasia (MADA; <a href="/entry/248370">248370</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'})"><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="#143" class="mim-tip-reference" title="Zirn, B., Kress, W., Grimm, T., Berthold, L. D., Neubauer, B., Kuchelmeister, K., Muller, U., Hahn, A. <strong>Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.</strong> Am. J. Med. Genet. 146A: 1049-1054, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348272</a>] [<a href="https://doi.org/10.1002/ajmg.a.32259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348272">Zirn et al. (2008)</a> reported a 7-year-old Turkish girl, born of consanguineous parents, who was homozygous for the R471C mutation. She had a phenotype most consistent with an atypical form of MADA, including lipodystrophy, a progeroid appearance, and congenital muscular dystrophy with rigid spine syndrome. These latter features were reminiscent of Emery-Dreifuss muscular dystrophy (<a href="/entry/181350">181350</a>), although there was no cardiac involvement. She presented at age 10 months with proximal muscle weakness, contractures, spinal rigidity, and a dystrophic skeletal muscle biopsy. Characteristic progeroid features and features of lipodystrophy and mandibuloacral dysplasia were noted at age 3 years and became more apparent with age. <a href="#143" class="mim-tip-reference" title="Zirn, B., Kress, W., Grimm, T., Berthold, L. D., Neubauer, B., Kuchelmeister, K., Muller, U., Hahn, A. <strong>Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.</strong> Am. J. Med. Genet. 146A: 1049-1054, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348272</a>] [<a href="https://doi.org/10.1002/ajmg.a.32259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348272">Zirn et al. (2008)</a> commented on the severity of the phenotype and emphasized the phenotypic variability in patients with LMNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0026 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57318642 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57318642;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs57318642?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57318642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57318642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015576 OR RCV000057324 OR RCV000192011 OR RCV001185736 OR RCV001223656 OR RCV002288492 OR RCV003319169 OR RCV003996098" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015576, RCV000057324, RCV000192011, RCV001185736, RCV001223656, RCV002288492, RCV003319169, RCV003996098" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015576...</a>
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<p>For discussion of the arg527-to-cys (R527C) mutation in the LMNA gene that was found in compound heterozygous state in a patient with mandibuloacral dysplasia (MADA; <a href="/entry/248370">248370</a>) by <a href="#12" class="mim-tip-reference" title="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://doi.org/10.1007/s10038-003-0025-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12768443">Cao and Hegele (2003)</a> and <a href="#10" class="mim-tip-reference" title="Brown, W. T. <strong>Personal Communication.</strong> Staten Island, N.Y. 1/12/2004."None>Brown (2004)</a>, see <a href="#0025">150330.0025</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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0027 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs60864230 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60864230;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs60864230?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60864230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60864230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male patient whose phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, and hepatic steatosis (FPLD2; <a href="/entry/151660">151660</a>), <a href="#16" class="mim-tip-reference" title="Caux, F., Dubosclard, E., Lascols, O., Buendia, B., Chazouilleres, O., Cohen, A., Courvalin, J.-C., Laroche, L., Capeau, J., Vigouroux, C., Christin-Maitre, S. <strong>A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.</strong> J. Clin. Endocr. Metab. 88: 1006-1013, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629077</a>] [<a href="https://doi.org/10.1210/jc.2002-021506" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629077">Caux et al. (2003)</a> found a heterozygous 398G-T transversion in exon 2 of the LMNA gene that resulted in an arg-to-leu change at codon 133 (R133L) in the dimerization rod domain of lamins A and C. The patient also had hypertrophic cardiomyopathy with valvular involvement and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadened the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the possibility of hypertrophic cardiomyopathy and skin involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629077" 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="#132" class="mim-tip-reference" title="Vigouroux, C., Caux, F. Capeau, J., Christin-Maitre, S., Cohen, A. <strong>LMNA mutations in atypical Werner's syndrome. (Letter)</strong> Lancet 362: 1585 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14615128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14615128</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14760-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14615128">Vigouroux et al. (2003)</a> emphasized that a striking feature in the patient reported by <a href="#16" class="mim-tip-reference" title="Caux, F., Dubosclard, E., Lascols, O., Buendia, B., Chazouilleres, O., Cohen, A., Courvalin, J.-C., Laroche, L., Capeau, J., Vigouroux, C., Christin-Maitre, S. <strong>A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.</strong> J. Clin. Endocr. Metab. 88: 1006-1013, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629077</a>] [<a href="https://doi.org/10.1210/jc.2002-021506" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629077">Caux et al. (2003)</a> was muscular hypertrophy of the limbs, which contrasts with the muscular atrophy usually present in Werner syndrome. Muscular hypertrophy, along with insulin-resistant diabetes and hypertriglyceridemia, is more often associated with LMNA-linked Dunnigan lipodystrophy. Fibroblasts from their patient showed nuclear abnormalities identical to those described in Dunnigan lipodystrophy (<a href="#131" class="mim-tip-reference" title="Vigouroux, C., Auclair, M., Dubosclard, E., Pouchelet, M., Capeau, J., Courvalin, J.-C., Buendia, B. <strong>Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.</strong> J. Cell Sci. 114: 4459-4468, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11792811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11792811</a>] [<a href="https://doi.org/10.1242/jcs.114.24.4459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11792811">Vigouroux et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12629077+11792811+14615128" 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 2 unrelated persons with a progeroid syndrome (see <a href="/entry/176670">176670</a>), <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> found heterozygosity for the R1333L mutation in the LMNA gene. One was a white Portuguese female who presented at the age of 9 years with short stature. She showed scleroderma-like skin changes and graying/thinning of hair. Type 2 diabetes developed at the age of 23 years. Hypogonadism, osteoporosis, and voice changes were also present. The other patient was an African American female in whom the diagnosis of a progeroid syndrome was made at the age of 18 years. Scleroderma-like skin, short stature, graying/thinning of hair, and type 2 diabetes at the age of 18 years were features. The deceased father, paternal aunt, and paternal grandmother of this patient were also diagnosed with severe insulin-resistant diabetes mellitus, suggesting that the R133L mutation might have been paternally inherited. It is noteworthy that a substitution in the same codon, R133P (<a href="#0032">150330.0032</a>), was reported in a 40-year-old patient with Emery-Dreifuss muscular dystrophy who had disease onset at age 7 years and atrial fibrillation at age 32 years (<a href="#9" class="mim-tip-reference" title="Brown, C. A., Lanning, R. W., McKinney, K. Q., Salvino, A. R., Cherniske, E., Crowe, C. A., Darras, B. T., Gominak, S., Greenberg, C. R., Grosmann, C., Heydemann, P., Mendell, J. R., Pober, B. R., Sasaki, T., Shapiro, F., Simpson, D. A., Suchowersky, O., Spence, J. E. <strong>Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.</strong> Am. J. Med. Genet. 102: 359-367, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11503164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11503164</a>] [<a href="https://doi.org/10.1002/ajmg.1463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11503164">Brown et al., 2001</a>). Although <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> designated these patients as having 'atypical Werner syndrome' (<a href="/entry/277700">277700</a>), <a href="#51" class="mim-tip-reference" title="Hegele, R. A. <strong>Drawing the line in progeria syndromes.</strong> Lancet 362: 416-417, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14097-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927424">Hegele (2003)</a> suggested that the patients more likely had late-onset Hutchinson-Gilford progeria syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11503164+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="#56" class="mim-tip-reference" title="Jacob, K. N., Baptista, F., dos Santos, H. G., Oshima, J., Agarwal, A. K., Garg, A. <strong>Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous arg133leu lamin A/C mutation.</strong> J. Clin. Endocr. Metab. 90: 6699-6706, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174718</a>] [<a href="https://doi.org/10.1210/jc.2005-0939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174718">Jacob et al. (2005)</a> studied the pattern of body fat distribution and metabolic abnormalities in the 2 patients with atypical Werner syndrome described by <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a>. Patient 1, an African American female, had normal body fat (27%) by dual energy X-ray absorptiometry (DEXA). However, magnetic resonance imaging (MRI) revealed relative paucity of subcutaneous fat in the distal extremities, with preservation of subcutaneous truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. In contrast, patient 2, a Caucasian female, had only 11.6% body fat as determined by DEXA and had generalized loss of subcutaneous and intraabdominal fat on MRI. She had hypertriglyceridemia and severe insulin-resistant diabetes requiring more than 200 U of insulin daily. Skin fibroblasts showed markedly abnormal nuclear morphology compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. <a href="#56" class="mim-tip-reference" title="Jacob, K. N., Baptista, F., dos Santos, H. G., Oshima, J., Agarwal, A. K., Garg, A. <strong>Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous arg133leu lamin A/C mutation.</strong> J. Clin. Endocr. Metab. 90: 6699-6706, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174718</a>] [<a href="https://doi.org/10.1210/jc.2005-0939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174718">Jacob et al. (2005)</a> concluded that atypical Werner syndrome associated with an R133L mutation in the LMNA gene is phenotypically heterogeneous. Furthermore, the severity of metabolic complications seemed to correlate with the extent of lipodystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16174718+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>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015598 OR RCV000057409 OR RCV000211788 OR RCV000687241 OR RCV001170451 OR RCV003318333 OR RCV004018635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015598, RCV000057409, RCV000211788, RCV000687241, RCV001170451, RCV003318333, RCV004018635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015598...</a>
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<p><a href="#109" class="mim-tip-reference" title="Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. <strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong> J. Med. Genet. 40: 560-567, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>] [<a href="https://doi.org/10.1136/jmg.40.8.560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920062">Sebillon et al. (2003)</a> described a family with a history of sudden cardiac death, congestive heart failure, and dilated cardiomyopathy (CMD1A; <a href="/entry/115200">115200</a>). Five affected members had a heterozygous 481G-A transition in exon 2 of the LMNA gene, resulting in a glu161-to-lys (E161K) mutation. Dilated cardiomyopathy was present in only 2 patients, in whom onset of the disease was characterized by congestive heart failure and atrial fibrillation (at 29 and 44 years, respectively); heart transplantation was performed in both patients (at 34 and 51 years of age). In the 3 other affected members, the onset of disease was also characterized by atrial fibrillation at 22, 49, and 63 years, but without dilated cardiomyopathy. A 16-year-old male and 12-year-old female were also heterozygous for the mutation, but had no signs or symptoms of heart disease. The 5 affected members were a mother and 2 daughters in 1 branch of the family and 2 brothers in another branch. Two cardiac deaths were reported in the family history: sudden death at 38 years and congestive heart failure at 68 years. No significant atrioventricular block was observed in the family, except in 1 patient for whom cardiac pacing was necessary at 67 years of age because of sinoatrial block coexisting with atrial fibrillation. <a href="#109" class="mim-tip-reference" title="Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. <strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong> J. Med. Genet. 40: 560-567, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>] [<a href="https://doi.org/10.1136/jmg.40.8.560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920062">Sebillon et al. (2003)</a> concluded that the phenotype in this family was characterized by early atrial fibrillation preceding or coexisting with dilated cardiomyopathy, without significant atrioventricular block, and without neuromuscular abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs57077886 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57077886;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs57077886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs57077886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015599 OR RCV000057387 OR RCV000502816 OR RCV000622546 OR RCV000755005" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015599, RCV000057387, RCV000502816, RCV000622546, RCV000755005" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015599...</a>
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<p><a href="#109" class="mim-tip-reference" title="Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. <strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong> J. Med. Genet. 40: 560-567, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>] [<a href="https://doi.org/10.1136/jmg.40.8.560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920062">Sebillon et al. (2003)</a> described a family in which 5 patients with dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>) were heterozygous for a 1-bp insertion, 28insA, in exon 1 of the LMNA gene. Three additional patients were considered as phenotypically affected with documented dilated cardiomyopathy but were not available for DNA analysis. In the family history, there were 3 cardiac sudden deaths before 55 years of age. In the patients with dilated cardiomyopathy, 3 had associated atrioventricular block requiring pacemaker implantation, 1 had premature ventricular beats leading to a cardioverter defibrillator implantation, and 1 had a mild form of skeletal muscular dystrophy (mild weakness and wasting of quadriceps muscles, as well as myogenic abnormalities on electromyogram). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0030 CARDIOMYOPATHY, DILATED, WITH HYPERGONADOTROPIC HYPOGONADISM</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28928903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928903;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28928903?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28928903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28928903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015600 OR RCV000057349" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015600, RCV000057349" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015600...</a>
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<p>In an Iranian female with short stature and a progeroid syndrome (see <a href="/entry/176670">176670</a>), <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> found a heterozygous de novo ala57-to-pro substitution (A57P) resulting from a 584G-C transversion in the LMNA gene. Onset occurred in her early teens, and she was 23 years old at diagnosis. Hypogonadism, osteoporosis, osteosclerosis of digits, and dilated cardiomyopathy were described. Although <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> designated this patient as having 'atypical Werner syndrome' (<a href="/entry/277700">277700</a>), <a href="#51" class="mim-tip-reference" title="Hegele, R. A. <strong>Drawing the line in progeria syndromes.</strong> Lancet 362: 416-417, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14097-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927424">Hegele (2003)</a> suggested that the patient more likely had late-onset Hutchinson-Gilford progeria syndrome. <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="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> suggested that the patient in whom <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> identified an A57P LMNA mutation had a distinct phenotype involving 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>
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<strong>.0031 HUTCHINSON-GILFORD PROGERIA SYNDROME, CHILDHOOD-ONSET</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60652225 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60652225;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60652225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60652225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015601 OR RCV000057403" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015601, RCV000057403" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015601...</a>
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<p>In a white Norwegian male with a progeroid syndrome (see <a href="/entry/176670">176670</a>), <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> found a leu140-to-arg (L140R) substitution resulting from an 834T-G transversion in the LMNA gene. The patient had onset at age 14 of cataracts, scleroderma-like skin, and graying/thinning of hair, as well as hypogonadism, osteoporosis, soft tissue calcification, and premature atherosclerosis. Aortic stenosis and insufficiency were also present. The patient died at the age of 36 years. Although <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> designated this patient as having 'atypical Werner syndrome' (<a href="/entry/277700">277700</a>), <a href="#51" class="mim-tip-reference" title="Hegele, R. A. <strong>Drawing the line in progeria syndromes.</strong> Lancet 362: 416-417, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)14097-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927424">Hegele (2003)</a> suggested that the patient more likely had late-onset Hutchinson-Gilford progeria syndrome. <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>
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<strong>.0032 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs60864230 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60864230;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs60864230?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60864230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60864230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015602 OR RCV000057398 OR RCV000686691" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015602, RCV000057398, RCV000686691" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015602...</a>
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<p>In a 40-year-old patient with Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>) who had disease onset at age 7 years and atrial fibrillation at age 32 years, <a href="#9" class="mim-tip-reference" title="Brown, C. A., Lanning, R. W., McKinney, K. Q., Salvino, A. R., Cherniske, E., Crowe, C. A., Darras, B. T., Gominak, S., Greenberg, C. R., Grosmann, C., Heydemann, P., Mendell, J. R., Pober, B. R., Sasaki, T., Shapiro, F., Simpson, D. A., Suchowersky, O., Spence, J. E. <strong>Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.</strong> Am. J. Med. Genet. 102: 359-367, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11503164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11503164</a>] [<a href="https://doi.org/10.1002/ajmg.1463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11503164">Brown et al. (2001)</a> found an arg133-to-pro (R133P) mutation in the LMNA gene. <a href="#19" 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. <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://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12927431">Chen et al. (2003)</a> noted that the same codon is involved in the arg133-to-leu (<a href="#0027">150330.0027</a>) mutation in atypical Werner syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11503164+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>
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<strong>.0033 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs56673169 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs56673169;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs56673169" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs56673169" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015603 OR RCV000057346" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015603, RCV000057346" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015603...</a>
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<p>In 4 affected members of a consanguineous family from north India with features of mandibuloacral dysplasia with type A lipodystrophy (MADA; <a href="/entry/248370">248370</a>). <a href="#95" 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. <strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 609-614, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15286156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15286156</a>] [<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15286156">Plasilova et al. (2004)</a> identified a homozygous 1626G-C transversion in exon 10 of the LMNA gene, resulting in a lys542-to-asn (K542N) substitution. The parents and 1 unaffected daughter were heterozygous for the mutation. Patients in this family showed uniform skeletal malformations such as acroosteolysis of the digits, micrognathia, and clavicular aplasia/hypoplasia, characteristic of mandibuloacral dysplasia. However, the patients also had classic features of Hutchinson-Gilford progeria syndrome (<a href="/entry/176670">176670</a>). <a href="#95" 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. <strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong> J. Med. Genet. 41: 609-614, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15286156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15286156</a>] [<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs58912633 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58912633;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs58912633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs58912633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015604 OR RCV000057405" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015604, RCV000057405" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015604...</a>
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<p>In a young girl with congenital muscular dystrophy and progeroid features (see <a href="/entry/613205">613205</a>), <a href="#62" class="mim-tip-reference" title="Kirschner, J., Brune, T., Wehnert, M., Denecke, J., Wasner, C., Feuer, A., Marquardt, T., Ketelsen, U.-P., Wieacker, P., Bonnemann, C. G., Korinthenberg, R. <strong>p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.</strong> Ann. Neurol. 57: 148-151, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15622532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15622532</a>] [<a href="https://doi.org/10.1002/ana.20359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15622532">Kirschner et al. (2005)</a> identified a 1824C-T transition in the LMNA gene, resulting in a de novo heterozygous missense mutation, ser143 to phe (S143F). The child presented during the first year of life with myopathy with marked axial weakness, feeding difficulties, poor head control and axial weakness. Progeroid features, including growth failure, sclerodermatous skin changes, and osteolytic lesions, developed later. At routine examination at age 8 years, she was found to have a mediolateral myocardial infarction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15622532" 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 cultured skin fibroblasts derived from the patient reported by <a href="#62" class="mim-tip-reference" title="Kirschner, J., Brune, T., Wehnert, M., Denecke, J., Wasner, C., Feuer, A., Marquardt, T., Ketelsen, U.-P., Wieacker, P., Bonnemann, C. G., Korinthenberg, R. <strong>p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.</strong> Ann. Neurol. 57: 148-151, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15622532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15622532</a>] [<a href="https://doi.org/10.1002/ana.20359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15622532">Kirschner et al. (2005)</a>, <a href="#60" class="mim-tip-reference" title="Kandert, S., Luke, Y., Kleinhenz, T., Neumann, S., Lu, W., Jaeger, V. M., Munck, M., Wehnert, M., Muller, C. R., Zhou, Z., Noegel, A. A., Dabauvalle, M.-C., Karakesisoglou, I. <strong>Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells.</strong> Hum. Molec. Genet. 16: 2944-2959, 2007. Note: Erratum: Hum. Molec. Genet. 17: 468 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881656</a>] [<a href="https://doi.org/10.1093/hmg/ddm255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881656">Kandert et al. (2007)</a> found dysmorphic nuclei with blebs and lobulations that accumulated progressively with cell passage. Immunofluorescent staining showed altered lamin A/C organization and aggregate formation. There was aberrant localization of lamin-associated proteins, particularly emerin (EMD; <a href="/entry/300384">300384</a>) and nesprin-2 (SYNE2; <a href="/entry/608442">608442</a>), which was reduced or absent from the nuclear envelope. However, a subset of mutant cells expressing the giant 800-kD isoform of SYNE2 showed a milder phenotype, suggesting that this isoform exerts a protective effect. Proliferating cells were observed to express the 800-kD SYNE2 isoform, whereas nonproliferating cells did not. In addition, mutant cells showed defects in the intranuclear organization of acetylated histones and RNA polymerase II compared to control cells. The findings indicated that the S143F mutant protein affects nuclear envelope architecture and composition, chromatin organization, gene expression, and transcription. The findings also implicated nesprin-2 as a structural reinforcer at the nuclear envelope. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15622532+17881656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs58048078 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58048078;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs58048078?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs58048078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs58048078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015605 OR RCV000057457 OR RCV005089263" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015605, RCV000057457, RCV005089263" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015605...</a>
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<p>In 9 affected members of Dutch family diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was later reclassified as Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>) by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#127" class="mim-tip-reference" title="van Engelen, B. G. M., Muchir, A., Hutchison, C. J., van der Kooi, A. J., Bonne, G., Lammens, M. <strong>The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene.</strong> Neurology 64: 374-376, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668447</a>] [<a href="https://doi.org/10.1212/01.WNL.0000149763.15180.00" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15668447">van Engelen et al. (2005)</a> identified a 777T-A transversion in the LMNA gene, resulting in a tyr259-to-ter substitution (Y259X). The heterozygous Y259X mutation led to a classic LGMD1B phenotype. One infant homozygous for the mutation was born of consanguineous parents who were both affected, and delivered at 30 weeks' gestational age by cesarean section because of decreasing cardiac rhythm. The infant died at birth from very severe generalized muscular dystrophy. Cultured skin fibroblasts from the infant showed complete absence of A-type lamins leading to disorganization of the lamina, alterations in the protein composition of the inner nuclear membrane, and decreased life span. <a href="#127" class="mim-tip-reference" title="van Engelen, B. G. M., Muchir, A., Hutchison, C. J., van der Kooi, A. J., Bonne, G., Lammens, M. <strong>The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene.</strong> Neurology 64: 374-376, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668447</a>] [<a href="https://doi.org/10.1212/01.WNL.0000149763.15180.00" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15668447">Van Engelen et al. (2005)</a> noted that the fibroblasts from this child showed remarkable similarity, in nuclear architectural defects and in decreased life span, to the fibroblasts of homozygous LMNA (L530P/L530P) mice (<a href="#85" class="mim-tip-reference" title="Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T., Stewart, C. L. <strong>A progeroid syndrome in mice is caused by defects in A-type lamins.</strong> Nature 423: 298-301, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12748643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12748643</a>] [<a href="https://doi.org/10.1038/nature01631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12748643">Mounkes et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+12748643+15668447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs113436208 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113436208;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs113436208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs113436208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015607 OR RCV000057377 OR RCV001847645" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015607, RCV000057377, RCV001847645" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015607...</a>
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In a premature infant (P1) who died at 6 months of age due to restrictive dermopathy (RSDM2; <a href="/entry/619793">619793</a>), <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> identified a heterozygous G-to-A transition at position 1 in the intron 11 donor site of the LMNA gene (IVS11+1G-A), resulting in loss of exon 11 from the transcript. The patient expressed lamins A and C and a truncated prelamin A. Patient cells showed an abnormal transcript with an in-frame deletion of the entire exon 11 (270 bp), predicted to cause an internal deletion of 90 residues corresponding to a large part of the globular domain (Gly567_Gln656del). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=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="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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649378">Barthelemy et al. (2015)</a> analyzed LMNA exon 11 transcripts in cells derived from the patient reported by <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a>. In addition to production of a normal full-length prelamin A transcript, there was a band corresponding to prelamin A(del50) (progerin), and an additional transcript correlation to prelamin A(del90) resulting from the skipping of all of exon 11. The prelamin A(del90) transcript was termed 'dermopathin.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15317753+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><p><strong><em>Hutchinson-Guilford Progeria Syndrome</em></strong></p><p>
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In a patient with an extremely severe form of Hutchinson-Guilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#84" 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. <strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong> Hum. Mutat. 28: 882-889, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>] [<a href="https://doi.org/10.1002/humu.20536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17469202">Moulson et al. (2007)</a> identified a heterozygous G-to-A transition at the +1 position of the donor splice site of intron 11 in the LMNA gene (1968+1G-A). RT-PCR studies showed a truncated protein product identical to that observed in HGPS cell lines with the common 1824C-T mutation (<a href="#0022">150330.0022</a>), indicating that the new mutation resulted in the abnormal use of the same cryptic exon 11 splice site. The findings were in contrast to those reported by <a href="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a>, who observed skipping of exon 11 with 1968+1G-A. Further quantitative studies of the patient's cells by <a href="#84" 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. <strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong> Hum. Mutat. 28: 882-889, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>] [<a href="https://doi.org/10.1002/humu.20536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17469202">Moulson et al. (2007)</a> found a 4.5-fold increase in the relative ratio of mutant mRNA and protein to wildtype prelamin A compared to typical HGPS cells. The findings were confirmed by Western blot analysis and provided an explanation for the severe phenotype observed in this patient. He had had abnormally thick and tight skin observed at 11 weeks of age, and developed more typical but severe progeroid features over time. He died of infection at age 3.5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15317753+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>
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<strong>.0037 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60580541 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60580541;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60580541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60580541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015608 OR RCV000057332 OR RCV002399329 OR RCV002467496 OR RCV003234906" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015608, RCV000057332, RCV002399329, RCV002467496, RCV003234906" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015608...</a>
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<p>In 2 unrelated Turkish patients with mandibuloacral dysplasia with type A lipodystrophy (MADA; <a href="/entry/248370">248370</a>), a 21-year-old woman previously described by <a href="#22" class="mim-tip-reference" title="Cogulu, O., Gunduz, C., Darcan, S., Kadioglu, B., Ozkinay, F., Ozkinay, C. <strong>Mandibuloacral dysplasia with absent breast development. (Letter)</strong> Am. J. Med. Genet. 119A: 391-392, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12784312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12784312</a>] [<a href="https://doi.org/10.1002/ajmg.a.10169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12784312">Cogulu et al. (2003)</a> and an 18-year-old man, <a href="#38" class="mim-tip-reference" title="Garg, A., Cogulu, O., Ozkinay, F., Onay, H., Agarwal, A. K. <strong>A novel homozygous ala529val LMNA mutation in Turkish patients with mandibuloacral dysplasia.</strong> J. Clin. Endocr. Metab. 90: 5259-5264, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998779</a>] [<a href="https://doi.org/10.1210/jc.2004-2560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15998779">Garg et al. (2005)</a> identified homozygosity for a 1586C-T transition in the LMNA gene, resulting in an ala529-to-val (A529V) substitution. Intragenic SNPs revealed a common haplotype spanning 2.5 kb around the mutated nucleotide in the parents of both patients, suggesting ancestral origin of the mutation. The female patient had no breast development despite normal menstruation, a phenotype different from that seen in women with the R527H mutation (<a href="#0021">150330.0021</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15998779+12784312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs56699480 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs56699480;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs56699480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs56699480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015609 OR RCV000057304 OR RCV004698335" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015609, RCV000057304, RCV004698335" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015609...</a>
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<p>In a German woman diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#102" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Botzenhart, E., Eggermann, T., Senderek, J., Schoser, B. G. H., Schroder, R., Wehnert, M., Wirth, B., Zerres, K. <strong>Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.</strong> Neurogenetics 8: 137-142, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17136397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17136397</a>] [<a href="https://doi.org/10.1007/s10048-006-0070-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17136397">Rudnik-Schoneborn et al. (2007)</a> identified a heterozygous 1477C-T transition in exon 8 of the LMNA gene, resulting in a gln493-to-ter (Q493X) substitution. She presented with slowly progressive proximal muscle weakness beginning in the lower extremities and later involving the upper extremities. EMG showed both neurogenic and myopathic defects in the quadriceps muscle. At age 53 years, she was diagnosed with atrioventricular conduction block and arrhythmia requiring pacemaker implantation. Family history showed that her mother had walking difficulties from age 40 years and died of a heart attack at age 54. Six other deceased family members had suspected cardiomyopathy without muscle involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+17136397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607543 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607543;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607543" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267607543" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015610 OR RCV000057307 OR RCV003581575" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015610, RCV000057307, RCV003581575" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015610...</a>
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<p><a href="#83" class="mim-tip-reference" title="Morel, C. F., Thomas, M. A., Cao, H., O'Neil, C. H., Pickering, J. G., Foulkes, W. D., Hegele, R. A. <strong>A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2.</strong> J. Clin. Endocr. Metab. 91: 2689-2695, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16636128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16636128</a>] [<a href="https://doi.org/10.1210/jc.2005-2746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16636128">Morel et al. (2006)</a> reported 2 sisters, the children of nonconsanguineous Punjabi parents, with familial partial lipodystrophy type 2 (FPLD2; <a href="/entry/151660">151660</a>). The first presented with acanthosis nigricans at age 5 years, diabetes with insulin resistance, hypertension, and hypertriglyceridemia at age 13 years, and partial lipodystrophy starting at puberty. Her sister and their mother had a similar metabolic profile and physical features, and their mother died of vascular disease at age 32 years. LMNA sequencing showed that the sisters were each heterozygous for a novel G-to-C mutation at the intron 8 consensus splice donor site, which was absent from the genomes of 300 healthy individuals. The retention of intron 8 in mRNA predicted a prematurely terminated lamin A isoform (516 instead of 664 amino acids) with 20 nonsense 3-prime terminal residues. The authors concluded that this was the first LMNA splicing mutation to be associated with FPLD2, and that it causes a severe clinical and metabolic phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16636128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs59886214 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs59886214;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs59886214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs59886214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015611 OR RCV000057362" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015611, RCV000057362" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015611...</a>
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<p>In a patient with a severe form of Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#84" 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. <strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong> Hum. Mutat. 28: 882-889, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>] [<a href="https://doi.org/10.1002/humu.20536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17469202">Moulson et al. (2007)</a> identified a de novo heterozygous 1821G-A transition in exon 11 of the LMNA gene, resulting in a val607-to-val (V607V) substitution. The 1821G-A mutation favored the use of the same cryptic splice site as the common 1824C-T mutation (<a href="#0022">150330.0022</a>) and produced the same resultant progerin product. However, the ratio of mutant to wildtype mRNA and protein was increased in the patient compared to typical HGPS cells. The patient had flexion contractures, thick and tight skin, and other severe progeroid features. He died of infection at 26 days of age. <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>
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<strong>.0041 CARDIOMYOPATHY, DILATED, 1A</strong>
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MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL, INCLUDED<br />
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LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs60890628 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60890628;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs60890628?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60890628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60890628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015612 OR RCV000015613 OR RCV000015614 OR RCV000041329 OR RCV000057351 OR RCV000617932 OR RCV000653881 OR RCV001188887 OR RCV001248900 OR RCV002221478 OR RCV002509159 OR RCV005042059" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015612, RCV000015613, RCV000015614, RCV000041329, RCV000057351, RCV000617932, RCV000653881, RCV001188887, RCV001248900, RCV002221478, RCV002509159, RCV005042059" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015612...</a>
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<p>In a 50-year-old Italian woman with sporadic dilated cardiomyopathy with conduction defects (CMD1A; <a href="/entry/115200">115200</a>), <a href="#119" class="mim-tip-reference" title="Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group. <strong>Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.</strong> J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12628721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12628721</a>] [<a href="https://doi.org/10.1016/s0735-1097(02)02954-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12628721">Taylor et al. (2003)</a> identified heterozygosity for a 1718C-T transition in exon 11 of the LMNA gene, resulting in a ser573-to-leu substitution at a highly conserved residue, predicted to affect the carboxyl tail of the lamin A isoform. The mutation was not found in the proband's 2 unaffected offspring or in 300 control chromosomes, but her unaffected 60-year-old sister also carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12628721" 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="#128" class="mim-tip-reference" title="Van Esch, H., Agarwal, A. K., Debeer, P., Fryns, J.-P., Garg, A. <strong>A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.</strong> J. Clin. Endocr. Metab. 91: 517-521, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278265</a>] [<a href="https://doi.org/10.1210/jc.2005-1297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278265">Van Esch et al. (2006)</a> analyzed the LMNA gene in a 44-year-old male of European descent with arthropathy, tendinous calcifications, and a progeroid appearance (see <a href="/entry/248370">248370</a>) and identified homozygosity for the S573L mutation. Progeroid features included a small pinched nose, small lips, micrognathia with crowded teeth, cataract, and alopecia. He also had generalized lipodystrophy, and sclerodermatous skin. The arthropathy affected predominantly the distal femora and proximal tibia in the knee with tendinous calcifications. However, he had normal clavicles and no evidence of acroosteolysis. The authors concluded that he had a novel phenotype. The patient's unaffected 15-year-old son was heterozygous for the mutation, which was not found in 450 control chromosomes. The authors noted that the patient had no evidence of cardiomyopathy and his 70-year-old mother, an obligate heterozygote, had no known cardiac problems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278265" 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 75-year-old European male with partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#66" class="mim-tip-reference" title="Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A. <strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong> Clin. Genet. 71: 183-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250669">Lanktree et al. (2007)</a> identified heterozygosity for the S573L mutation in the LMNA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0042 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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LMNA, ASP230ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61214927 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61214927;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61214927" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs61214927" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015615 OR RCV000057443" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015615, RCV000057443" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015615...</a>
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<p>In a 46-year-old South Asian female with partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#66" class="mim-tip-reference" title="Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A. <strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong> Clin. Genet. 71: 183-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250669">Lanktree et al. (2007)</a> identified heterozygosity for a 688G-A transition in exon 4 of the LMNA gene, resulting in an asp230-to-asn (D230N) substitution at a conserved residue located 5-prime to the nuclear localization signal. The mutation, predicted to affect only the lamin A isoform, was not found in 200 controls of multiple ethnic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0043 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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LMNA, ARG399CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs58672172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58672172;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs58672172?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs58672172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs58672172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015616 OR RCV000057255 OR RCV000653937 OR RCV001174241 OR RCV001188431 OR RCV001257937 OR RCV002336085 OR RCV005042060" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015616, RCV000057255, RCV000653937, RCV001174241, RCV001188431, RCV001257937, RCV002336085, RCV005042060" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015616...</a>
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<p>In a 50-year-old European female with partial lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>), <a href="#66" class="mim-tip-reference" title="Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A. <strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong> Clin. Genet. 71: 183-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250669">Lanktree et al. (2007)</a> identified heterozygosity for a 1195C-T transition in exon 7 of the LMNA gene, resulting in an arg399-to-cys (R399C) substitution at a conserved residue located 5-prime to the nuclear localization signal. The mutation, predicted to affect only the lamin A isoform, was not found in 200 controls of multiple ethnic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250669" 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="#29" class="mim-tip-reference" title="Decaudain, A., Vantyghem, M.-C., Guerci, B., Hecart, A.-C., Auclair, M., Reznik, Y., Narbonne, H., Ducluzeau, P.-H., Donadille, B., Lebbe, C., Bereziat, V., Capeau, J., Lascols, O., Vigouroux, C. <strong>New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.</strong> J. Clin. Endocr. Metab. 92: 4835-4844, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17711925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17711925</a>] [<a href="https://doi.org/10.1210/jc.2007-0654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17711925">Decaudain et al. (2007)</a> identified a heterozygous R399 mutation in a woman with severe metabolic syndrome. She was diagnosed with insulin-resistant diabetes at age 32. Chronic hyperglycemia led to retinopathy, peripheral neuropathy, and renal failure. She had severe hypertriglyceridemia and diffuse atherosclerosis, requiring coronary artery bypass at age 49. Physical examination revealed android fat distribution with lipoatrophy of lower limbs and calves hypertrophy without any muscle weakness. Her mother and a brother had diabetes and died several years earlier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17711925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0044 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL</strong>
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LMNA, VAL440MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912493 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912493;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015617 OR RCV000057268 OR RCV000552191 OR RCV001172618 OR RCV001186220 OR RCV001264435 OR RCV002381252 OR RCV003996102 OR RCV005049339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015617, RCV000057268, RCV000552191, RCV001172618, RCV001186220, RCV001264435, RCV002381252, RCV003996102, RCV005049339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015617...</a>
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<p>In a 27-year-old Italian woman with a mandibuloacral dysplasia type A (MADA; <a href="/entry/248370">248370</a>)-like phenotype, <a href="#72" class="mim-tip-reference" title="Lombardi, F., Gullotta, F., Columbaro, M., Filareto, A., D'Adamo, M., Vielle, A., Guglielmi, V., Nardone, A. M., Azzolini, V., Grosso, E., Lattanzi, G., D'Apice, M. R., Masala, S., Maraldi, N. M., Sbraccia, P., Novelli, G. <strong>Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.</strong> J. Clin. Endocr. Metab. 92: 4467-4471, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17848409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17848409</a>] [<a href="https://doi.org/10.1210/jc.2007-0116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17848409">Lombardi et al. (2007)</a> found compound heterozygosity for missense mutations in the LMNA cDNA: a G-to-A transition at position 1318 in exon 7 that gave rise to a val-to-met substitution at codon 440 (V440M), and an R527H substitution (<a href="#0021">150330.0021</a>). Each healthy parent was a simple heterozygote for one or the other mutation. The apparent MADA phenotype was associated with muscular hyposthenia and generalized hypotonia. Clavicular hypoplasia and metabolic imbalances were absent. <a href="#72" class="mim-tip-reference" title="Lombardi, F., Gullotta, F., Columbaro, M., Filareto, A., D'Adamo, M., Vielle, A., Guglielmi, V., Nardone, A. M., Azzolini, V., Grosso, E., Lattanzi, G., D'Apice, M. R., Masala, S., Maraldi, N. M., Sbraccia, P., Novelli, G. <strong>Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.</strong> J. Clin. Endocr. Metab. 92: 4467-4471, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17848409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17848409</a>] [<a href="https://doi.org/10.1210/jc.2007-0116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17848409">Lombardi et al. (2007)</a> hypothesized that lack of homozygosity for the R527H mutation attenuated the MADA phenotype, while the V440M mutation may have contributed to both the muscle phenotype and the pathogenic effect of the single R527H mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17848409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0045 HEART-HAND SYNDROME, SLOVENIAN TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267607582 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607582;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs267607582?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267607582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015618 OR RCV000057337" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015618, RCV000057337" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015618...</a>
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<p>In affected members of a Slovenian family with heart-hand syndrome (<a href="/entry/610140">610140</a>), originally reported by <a href="#116" class="mim-tip-reference" title="Sinkovec, M., Petrovic, D., Volk, M., Peterlin, B. <strong>Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly: a new type of heart-hand syndrome?</strong> Clin. Genet. 68: 155-160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996213</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00476.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996213">Sinkovec et al. (2005)</a>, <a href="#100" class="mim-tip-reference" title="Renou, L., Stora, S., Yaou, R. B., Volk, M., Sinkovec, M., Demay, L., Richard, P., Peterlin, B., Bonne, G. <strong>Heart-hand syndrome of Slovenian type: a new kind of laminopathy. (Letter)</strong> J. Med. Genet. 45: 666-671, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18611980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18611980</a>] [<a href="https://doi.org/10.1136/jmg.2008.060020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18611980">Renou et al. (2008)</a> identified heterozygosity for a T-G transversion in intron 9 of the LMNA gene (IVS9-12T-G), predicted to cause a frameshift and premature termination in exon 10, with the addition of 14 new amino acids at the C terminus. The mutation was not found in unaffected family members or in 100 healthy controls. Analysis of fibroblasts from 2 affected individuals confirmed the presence of truncated protein and revealed aberrant localization of lamin A/C accumulated in intranuclear foci as well as dysmorphic nuclei with nuclear envelope herniations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15996213+18611980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0046 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912494 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912494;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912494?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015619 OR RCV000057331" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015619, RCV000057331" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015619...</a>
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<p>In a 56-year-old Japanese woman, born of consanguineous parents, with mandibuloacral dysplasia and type A lipodystrophy (MADA; <a href="/entry/248370">248370</a>), <a href="#63" class="mim-tip-reference" title="Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimura, G., Kato, H., Fukushima, Y. <strong>Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.</strong> Am. J. Med. Genet. 143A: 2598-2603, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935239</a>] [<a href="https://doi.org/10.1002/ajmg.a.31983" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935239">Kosho et al. (2007)</a> identified a homozygous 1585G-A transition in exon 9 of the LMNA gene, resulting in an ala529-to-thr (A529T) substitution. The authors stated that she was the oldest reported patient with the disorder. In addition to classic MAD with lipodystrophy type A phenotype, including progeroid appearance, acroosteolysis of the distal phalanges, and loss of subcutaneous fat in the limbs, she had severe progressive destructive skeletal and osteoporotic changes. Vertebral collapse led to paralysis. However, <a href="#63" class="mim-tip-reference" title="Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimura, G., Kato, H., Fukushima, Y. <strong>Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.</strong> Am. J. Med. Genet. 143A: 2598-2603, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935239</a>] [<a href="https://doi.org/10.1002/ajmg.a.31983" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935239">Kosho et al. (2007)</a> also noted that other factors may have contributed to the severe osteoporosis observed in this patient. Another mutation in this codon, A529V (<a href="#0037">150330.0037</a>), results in a similar phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0047 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912495 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912495;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015620 OR RCV000057237" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015620, RCV000057237" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015620...</a>
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<p>In a 7-year-old boy with a LMNA-related congenital muscular dystrophy (<a href="/entry/613205">613205</a>), <a href="#96" class="mim-tip-reference" title="Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others. <strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong> Ann. Neurol. 64: 177-186, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>] [<a href="https://doi.org/10.1002/ana.21417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551513">Quijano-Roy et al. (2008)</a> identified a de novo heterozygous mutation in exon 6 of the LMNA gene, resulting in a leu380-to-ser (L380S) substitution. He showed decreased movements in utero, hypotonia, talipes foot deformities, no head or trunk control, distal joint contractures, respiratory insufficiency, and paroxysmal atrial tachycardia. Serum creatine kinase was increased, and muscle biopsy showed dystrophic changes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0048 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912496 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912496;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912496" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912496" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015621 OR RCV000057452 OR RCV000814531" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015621, RCV000057452, RCV000814531" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015621...</a>
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<p>In a 9-year-old girl with congenital muscular dystrophy (<a href="/entry/613205">613205</a>), <a href="#96" class="mim-tip-reference" title="Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others. <strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong> Ann. Neurol. 64: 177-186, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>] [<a href="https://doi.org/10.1002/ana.21417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551513">Quijano-Roy et al. (2008)</a> identified a de novo heterozygous mutation in exon 4 of the LMNA gene, resulting in an arg249-to-trp (R249W) substitution. She presented at age 3 to 6 months with axial weakness and talipes foot deformities. She lost head support at 9 months, had respiratory insufficiency, joint contractures, and axial and limb muscle weakness. A de novo heterozygous R249W mutation was also identified in an unrelated 3-year-old boy with congenital LGMD1B who showed decreased movements in utero, hypotonia, distal contractures, no head or trunk control, and respiratory insufficiency. Both patients had increased serum creatine kinase and showed myopathic changes on EMG studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551513" 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="#106" class="mim-tip-reference" title="Scharner, J., Brown, C. A., Bower, M., Iannaccone, S. T., Khatri, I. A., Escolar, D., Gordon, E., Felice, K., Crowe, C. A., Grosmann, C., Meriggioli, M. N., Asamoah, A., Gordon, O., Gnocchi, V. F., Ellis, J. A., Mendell, J. R., Zammit, P. S. <strong>Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.</strong> Hum. Mutat. 32: 152-167, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20848652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20848652</a>] [<a href="https://doi.org/10.1002/humu.21361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20848652">Scharner et al. (2011)</a> found that transfection of the R249W mutation into cells resulted in increased expression of mutant LMNA, mislocalization of the protein in the nucleus, abnormal nuclear morphology with lobules, and mislocalization of lamin B (LMNB; <a href="/entry/150340">150340</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20848652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60458016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60458016;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60458016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60458016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015622 OR RCV000015623 OR RCV000057227 OR RCV000470514 OR RCV000502108 OR RCV001420791" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015622, RCV000015623, RCV000057227, RCV000470514, RCV000502108, RCV001420791" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015622...</a>
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<p><a href="#80" class="mim-tip-reference" title="Mercuri, E., Poppe, M., Quinlivan, R., Messina, S., Kinali, M., Demay, L., Bourke, J., Richard, P., Sewry, C., Pike, M., Bonne, G., Muntoni, F., Bushby, K. <strong>Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.</strong> Arch. Neurol. 61: 690-694, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148145</a>] [<a href="https://doi.org/10.1001/archneur.61.5.690" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15148145">Mercuri et al. (2004)</a> identified a de novo heterozygous 1072G-A transition in exon 5 of the LMNA gene, resulting in a glu358-to-lys (E358K) substitution, in 5 unrelated patients with muscular dystrophy. Three patients had the common phenotype of autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; <a href="/entry/181350">181350</a>), 1 was diagnosed with early-onset limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as EDMD2 by <a href="#118" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, and the last had had a more severe disorder consistent with congenital muscular dystrophy (<a href="/entry/613205">613205</a>). The mutation was not identified in 150 controls. The patient with LGMD1B also had cardiac conduction abnormalities, respiratory failure, and features of lipodystrophy (FPLD2; <a href="/entry/151660">151660</a>). <a href="#80" class="mim-tip-reference" title="Mercuri, E., Poppe, M., Quinlivan, R., Messina, S., Kinali, M., Demay, L., Bourke, J., Richard, P., Sewry, C., Pike, M., Bonne, G., Muntoni, F., Bushby, K. <strong>Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.</strong> Arch. Neurol. 61: 690-694, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148145</a>] [<a href="https://doi.org/10.1001/archneur.61.5.690" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15148145">Mercuri et al. (2004)</a> commented on the extreme phenotypic variability associated with this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+15148145" 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 unrelated patients with LMNA-related congenital muscular dystrophy, <a href="#96" class="mim-tip-reference" title="Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others. <strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong> Ann. Neurol. 64: 177-186, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>] [<a href="https://doi.org/10.1002/ana.21417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551513">Quijano-Roy et al. (2008)</a> identified a de novo heterozygous mutation in exon 6 of the LMNA gene, resulting in a glu358-to-lys (E358K) substitution. Three patients presented before 1 year of age with hypotonia and later developed head drop with neck muscle weakness. There was delayed motor development with early loss of ambulation, distal limb contractures, axial and limb muscle weakness, respiratory insufficiency requiring mechanical ventilation, increased serum creatine kinase, and dystrophic changes on muscle biopsy. One patient developed ventricular tachycardia at age 20 years. The fourth patient with congenital LGMD1B had decreased fetal movements and presented at age 3 to 6 months with hypotonia, loss of head control, and delayed motor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs60872029 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60872029;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs60872029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs60872029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015625 OR RCV000057490 OR RCV000459386" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015625, RCV000057490, RCV000459386" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015625...</a>
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<p>In an 18-month-old boy with LMNA-related congenital muscular dystrophy (<a href="/entry/613205">613205</a>), <a href="#24" class="mim-tip-reference" title="D'Amico, A., Haliloglu, G., Richard, P., Talim, B., Maugenre, S., Ferreiro, A., Guicheney, P., Menditto, I., Benedetti, S., Bertini, E., Bonne, G., Topaloglu, H. <strong>Two patients with 'dropped head syndrome' due to mutations in LMNA or SEPN1 genes.</strong> Neuromusc. Disord. 15: 521-524, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15961312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15961312</a>] [<a href="https://doi.org/10.1016/j.nmd.2005.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15961312">D'Amico et al. (2005)</a> identified a de novo heterozygous 3-bp deletion (94delAAG) in exon 1 of the LMNA gene, resulting in the deletion of lys32. Although he had normal early motor development, he showed prominent neck extensor weakness resulting in a 'dropped head' phenotype at age 1 year. He was able to stand independently but had some difficulty walking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15961312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs142000963 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs142000963;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs142000963?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs142000963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs142000963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015626 OR RCV000041340 OR RCV000057374 OR RCV000144868 OR RCV000148602 OR RCV000245284 OR RCV000755679 OR RCV000771143 OR RCV001084244 OR RCV001174411 OR RCV002467497 OR RCV003224100 OR RCV004528114" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015626, RCV000041340, RCV000057374, RCV000144868, RCV000148602, RCV000245284, RCV000755679, RCV000771143, RCV001084244, RCV001174411, RCV002467497, RCV003224100, RCV004528114" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015626...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to various phenotypes has not been confirmed.</p><p>An arg644-to-cys (R644C) mutation in the LMNA gene has been found in several different phenotypic presentations (<a href="#40" class="mim-tip-reference" title="Genschel, J., Bochow, B., Kuepferling, S., Ewert, R., Hetzer, R., Lochs, H., Schmidt, H. H.-J. <strong>A R644C mutation within lamin A extends the mutations causing dilated cardiomyopathy.</strong> Hum. Genet. 17: 154, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180602</a>] [<a href="https://doi.org/10.1002/1098-1004(200102)17:2<154::AID-HUMU11>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11180602">Genschel et al., 2001</a>; <a href="#79" class="mim-tip-reference" title="Mercuri, E., Brown, S. C., Nihoyannopoulos, P., Poulton, J., Kinali, M., Richard, P., Piercy, R. J., Messina, S., Sewry, C., Burke, M. M., McKenna, W., Bonne, G., Muntoni, F. <strong>Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.</strong> Muscle Nerve 31: 602-609, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15770669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15770669</a>] [<a href="https://doi.org/10.1002/mus.20293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15770669">Mercuri et al., 2005</a>; <a href="#98" class="mim-tip-reference" title="Rankin, J., Auer-Grumbach, M., Bagg, W., Colclough, K., Duong, N. T., Fenton-May, J., Hattersley, A., Hudson, J., Jardine, P., Josifova, D., Longman, C., McWilliam, R., Owen, K., Walker, M., Wehnert, M., Ellard, S. <strong>Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.</strong> Am. J. Med. Genet. 146A: 1530-1542, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478590</a>] [<a href="https://doi.org/10.1002/ajmg.a.32331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18478590">Rankin et al., 2008</a>), but the pathogenicity of the mutation has not been confirmed (<a href="#82" class="mim-tip-reference" title="Moller, D. V., Pham, T. T., Gustafsson, F., Hedley, P., Ersboll, M. K., Bundgaard, H., Andersen, C. B., Torp-Pedersen, C., Kober, L., Christiansen, M. <strong>The role of lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy.</strong> Europ. J. Heart Fail. 11: 1031-1035, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19875404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19875404</a>] [<a href="https://doi.org/10.1093/eurjhf/hfp134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19875404">Moller et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15770669+11180602+19875404+18478590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a German patient with dilated cardiomyopathy with no history of conduction system disease (see <a href="/entry/115200">115200</a>), <a href="#40" class="mim-tip-reference" title="Genschel, J., Bochow, B., Kuepferling, S., Ewert, R., Hetzer, R., Lochs, H., Schmidt, H. H.-J. <strong>A R644C mutation within lamin A extends the mutations causing dilated cardiomyopathy.</strong> Hum. Genet. 17: 154, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180602</a>] [<a href="https://doi.org/10.1002/1098-1004(200102)17:2<154::AID-HUMU11>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11180602">Genschel et al. (2001)</a> identified heterozygosity for a 1930C-T transition in exon 11 of the LMNA gene resulting in an R644C substitution in the C-terminal domain of lamin A. The authors noted that the mutation is solely within lamin A, but not lamin C, whereas previously reported mutations causing dilated cardiomyopathy are located more in the rod domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11180602" 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="#79" class="mim-tip-reference" title="Mercuri, E., Brown, S. C., Nihoyannopoulos, P., Poulton, J., Kinali, M., Richard, P., Piercy, R. J., Messina, S., Sewry, C., Burke, M. M., McKenna, W., Bonne, G., Muntoni, F. <strong>Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.</strong> Muscle Nerve 31: 602-609, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15770669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15770669</a>] [<a href="https://doi.org/10.1002/mus.20293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15770669">Mercuri et al. (2005)</a> identified heterozygosity for the R644C mutation in 4 patients with skeletal and cardiac muscle involvement of varying severity. In 1 patient, the mutation was found in the affected brother and the unaffected father, and was not found in the affected mother. The mutation was not found in 100 unrelated control subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15770669" 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="#98" class="mim-tip-reference" title="Rankin, J., Auer-Grumbach, M., Bagg, W., Colclough, K., Duong, N. T., Fenton-May, J., Hattersley, A., Hudson, J., Jardine, P., Josifova, D., Longman, C., McWilliam, R., Owen, K., Walker, M., Wehnert, M., Ellard, S. <strong>Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.</strong> Am. J. Med. Genet. 146A: 1530-1542, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478590</a>] [<a href="https://doi.org/10.1002/ajmg.a.32331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18478590">Rankin et al. (2008)</a> described 9 patients in 8 families with the R644C mutation. Patients 1 and 2 presented with lipodystrophy and insulin resistance; patient 1 also had focal segmental glomerulosclerosis. Patient 3 presented with motor neuropathy, patient 4 with arthrogryposis and dilated cardiomyopathy with left ventricular noncompaction, patient 5 with severe scoliosis and contractures, patient 6 with limb-girdle weakness, and patient 7 with hepatic steatosis and insulin resistance. Patients 8 and 9 were brothers who had proximal weakness and contractures. The same mutation was identified in 9 unaffected individuals in these 9 families, but was not detected in 200 German and 300 British controls. <a href="#98" class="mim-tip-reference" title="Rankin, J., Auer-Grumbach, M., Bagg, W., Colclough, K., Duong, N. T., Fenton-May, J., Hattersley, A., Hudson, J., Jardine, P., Josifova, D., Longman, C., McWilliam, R., Owen, K., Walker, M., Wehnert, M., Ellard, S. <strong>Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.</strong> Am. J. Med. Genet. 146A: 1530-1542, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478590</a>] [<a href="https://doi.org/10.1002/ajmg.a.32331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18478590">Rankin et al. (2008)</a> suggested that extreme phenotypic diversity and low penetrance are associated with the R644C mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18478590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0052 CARDIOMYOPATHY, DILATED, WITH HYPERGONADOTROPIC HYPOGONADISM</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs58922911 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58922911;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs58922911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs58922911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015627 OR RCV000057357" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015627, RCV000057357" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015627...</a>
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<p>In a 17-year-old Caucasian female with dilated cardiomyopathy and ovarian failure (<a href="/entry/212112">212112</a>), <a href="#92" class="mim-tip-reference" title="Nguyen, D., Leistritz, D. F., Turner, L., MacGregor, D., Ohson, K., Dancey, P., Martin, G. M., Oshima, J. <strong>Collagen expression in fibroblasts with a novel LMNA mutation.</strong> Biochem. Biophys. Res. Commun. 352: 603-608, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17150192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17150192</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17150192[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.11.070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17150192">Nguyen et al. (2007)</a> identified heterozygosity for a de novo 176T-C transition in exon 1 of the LMNA gene, predicted to result in a leu59-to-arg (L59R) substitution. Analysis of nuclear morphology in patient fibroblasts showed more irregularity and variation than that of control fibroblasts, with denting, blebbing, and irregular margins. The mutation was not found in the unaffected parents or in 116 population-based controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17150192" 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 15-year-old Caucasian girl with dilated cardiomyopathy and ovarian failure who died from an arrhythmia while awaiting cardiac transplantation, <a href="#78" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. <strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong> Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>] [<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19283854">McPherson et al. (2009)</a> identified heterozygosity for the L59R mutation in the LMNA gene. The mutation was presumed to be de novo, although the unaffected parents declined DNA testing. The patient also had a healthy older sister, and there was no family history of cardiomyopathy or hypogonadism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19283854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs56984562 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs56984562;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs56984562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs56984562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs with dilated cardiomyopathy (CMD1A; <a href="/entry/115200">115200</a>), <a href="#75" class="mim-tip-reference" title="Malek, L. A., Labib, S., Mazurkiewicz, L., Saj, M., Ploski, R., Tesson, F., Bilinska, Z. T. <strong>A new c.1621 C-G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation.</strong> J. Hum. Genet. 56: 83-86, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21085127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21085127</a>] [<a href="https://doi.org/10.1038/jhg.2010.137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21085127">Malek et al. (2011)</a> identified a heterozygous 1621C-G transversion in exon 10 of the LMNA gene, resulting in an arg541-to-gly (R541G) substitution in the C-terminal tail region. The 23-year-old male proband had a history of paroxysmal atrioventricular nodal reentrant tachycardia and was found by echocardiogram to have dilation of the left ventricle and global hypokinesis. Cardiac MRI showed discrete regional areas of akinesis with muscle thinning in the left ventricle and marked hypertrabeculation in dysfunctional regions, as well as evidence of fibrosis. The proband's sister had sinus bradycardia and supraventricular and ventricular arrhythmias, but normal echocardiogram and cardiac MRI. The sibs' father and paternal aunt had both died of dilated cardiomyopathy. In vitro functional expression studies showed that the R541G mutant resulted in the formation of abnormal lamin aggregates, most of which were sickle-shaped, suggesting aberrant formation of the inner nuclear lamina from misassembled lamin dimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21085127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034134 OR RCV000190400 OR RCV001178806 OR RCV001384595 OR RCV001781340 OR RCV001814022 OR RCV003996150 OR RCV005042105" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034134, RCV000190400, RCV001178806, RCV001384595, RCV001781340, RCV001814022, RCV003996150, RCV005042105" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034134...</a>
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<p>In 4 sibs, born of consanguineous Spanish parents, with autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; <a href="/entry/616516">616516</a>), <a href="#57" class="mim-tip-reference" title="Jimenez-Escrig, A., Gobernado, I., Garcia-Villanueva, M., Sanchez-Herranz, A. <strong>Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing.</strong> Muscle Nerve 45: 605-610, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22431096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22431096</a>] [<a href="https://doi.org/10.1002/mus.22324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22431096">Jimenez-Escrig et al. (2012)</a> identified a homozygous c.674G-A transition in exon 4 of the LMNA gene, resulting in an arg225-to-gln (R225Q) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in 200 control chromosomes. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22431096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797044487 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044487;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs797044487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs797044487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs and a mother with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>), <a href="#53" 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. <strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong> Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.34336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065502">Hisama et al. (2011)</a> identified a heterozygous c.1968G-A transition at the last nucleotide of exon 11 of the LMNA gene, predicted to result in a nonsynonymous gln656-to-gln (Q656Q) substitution. However, analysis of patient cells showed that the mutation affected splicing, resulting in an in-frame deletion of 150 nucleotides that corresponded to progerin (see <a href="#0022">150330.0022</a>) observed in patients with HGPS. The ratio of progerin/lamin A was 0.15, which is one-quarter that observed in HGPS cells. The patients had adult-onset severe coronary artery disease and a progeroid appearance. <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="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649378">Barthelemy et al. (2015)</a> identified a heterozygous c.1968G-A (c.1968G-A, NM_1707073) transition in the LMNA gene in another patient with adult-onset HGPS manifest as progeroid features and severe atherosclerosis necessitating bypass surgery at age 35. Analysis of LMNA exon 11 transcripts in patient cells showed the production of a normal full-length prelamin A transcript, a band corresponding to prelamin A(del50) (progerin), and an additional transcript corresponding to prelamin A(del90) resulting from the skipping of all of exon 11. <a href="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> (see <a href="#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). In fibroblasts derived from 2 of the patients reported by <a href="#53" 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. <strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong> Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.34336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065502">Hisama et al. (2011)</a>, <a href="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649378">Barthelemy et al. (2015)</a> presented preliminary evidence that a polymorphism in exon 10 of the LMNA gene (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs4641;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs4641</a>) may influence the production of various transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15317753+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>
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<strong>.0056 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797044488 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044488;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs797044488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs797044488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000190823 OR RCV000192020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190823, RCV000192020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190823...</a>
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<p>In a woman with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>) manifest as severe coronary artery disease and progeroid features, <a href="#53" 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. <strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong> Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.34336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065502">Hisama et al. (2011)</a> identified a heterozygous G-to-A transition (c.1968+5G-A) in the donor splice site of intron 11 of the LMNA gene, resulting in a 150-bp deletion. Western blot analysis of patient cells showed progerin at lower levels than in classic HGPS patient cells. <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="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649378">Barthelemy et al. (2015)</a> identified a heterozygous c.1968+5G-A transition (c.1968+5G-A, NM_170707.3) in the LMNA gene in another patient with atypical HGPS manifest as progeroid features and cardiac disease. He died at age 17 years of hypertrophic cardiomyopathy and aortic and mitral valve stenosis. Analysis of LMNA exon 11 transcripts in patient cells showed the production of 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="#2" 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. <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://doi.org/10.1038/ejhg.2014.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#91" 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. <strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong> Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>] [<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317753">Navarro et al. (2004)</a> (see <a href="#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). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15317753+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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<strong>.0057 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs79907212 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs79907212;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs79907212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs79907212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000201431" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201431" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201431</a>
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<p>In affected members of a family with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; <a href="/entry/176670">176670</a>) manifest as premature cutaneous and cardiac aging, <a href="#61" 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. <strong>LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.</strong> Am. J. Med. Genet. 161A: 1599-1611, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23666920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23666920</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.35971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23666920">Kane et al. (2013)</a> identified a heterozygous c.899A-G transition in the LMNA gene, resulting in an asp300-to-gly (D300G) substitution at a highly conserved residue in the second coiled-coil domain. The mutation, which segregated with the disorder in the family, was not found in the 1000 Genomes Project (Phase 1) or Exome Variant Server databases or in 100 control chromosomes. The affected domain mediates lamin protein dimerization and promotes filament formation. 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>
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<strong>.0058 HEART-HAND SYNDROME, SLOVENIAN TYPE</strong>
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LMNA, ARG335TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs386134243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386134243;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs386134243?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs386134243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs386134243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000030145 OR RCV000182368 OR RCV000546102 OR RCV000620788 OR RCV000721960 OR RCV000844672 OR RCV000845456 OR RCV000852407 OR RCV001196390 OR RCV002477025 OR RCV003149579 OR RCV003492303 OR RCV004532421" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030145, RCV000182368, RCV000546102, RCV000620788, RCV000721960, RCV000844672, RCV000845456, RCV000852407, RCV001196390, RCV002477025, RCV003149579, RCV003492303, RCV004532421" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030145...</a>
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<p>In affected members of a family with Slovenian-type heart-hand syndrome, <a href="#142" class="mim-tip-reference" title="Zaragoza, M. V., Hakim, S. A., Hoang, V., Elliott, A. M. <strong>Heart-hand syndrome IV: a second family with LMNA-related cardiomyopathy and brachydactyly. (Letter)</strong> Clin. Genet. 91: 499-500, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27723096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27723096</a>] [<a href="https://doi.org/10.1111/cge.12870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27723096">Zaragoza et al. (2017)</a> identified heterozygosity for a c.1003C-T transition in the LMNA gene, resulting in an arg335-to-trp (R335W) substitution, that segregated with the disorder in the family. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27723096" 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="seeAlso" class="mim-anchor"></a>
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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>See Also:</strong>
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<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
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<a href="#Krohne1986" class="mim-tip-reference" title="Krohne, G., Benavente, R. <strong>The nuclear lamins: a multigene family of proteins in evolution and differentiation.</strong> Exp. Cell Res. 162: 1-10, 1986.">Krohne and Benavente (1986)</a>; <a href="#Lebel1987" class="mim-tip-reference" title="Lebel, S., Raymond, Y. <strong>Lamin A is not synthesized as a larger precursor polypeptide.</strong> Biochem. Biophys. Res. Commun. 149: 417-423, 1987.">Lebel and Raymond (1987)</a>
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<br />
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<strong>REFERENCES</strong>
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</h4>
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<a id="1" class="mim-anchor"></a>
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<a id="Arimura2005" class="mim-anchor"></a>
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Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacene, E., Fromes, Y., Toussaint, M., Mura, A.-M., Keller, D. I., Amthor, H., Isnard, R., Malissen, M., Schwartz, K., Bonne, G.
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<strong>Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.</strong>
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Hum. Molec. Genet. 14: 155-169, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15548545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15548545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15548545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi017" 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.
|
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<strong>Truncated prelamin A expression in HGPS-like patients: a transcriptional study.</strong>
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Europ. J. Hum. Genet. 23: 1051-1061, 2015.
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[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://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>]
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[<a href="https://doi.org/10.1038/ejhg.2014.239" target="_blank">Full Text</a>]
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<a id="Ben Yaou2007" class="mim-anchor"></a>
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<div class="">
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Ben Yaou, R., Toutain, A., Arimura, T., Demay, L., Massart, C., Peccate, C., Muchir, A., Llense, S., Deburgreave, N., Leturcq, F., Litim, K. E., Rahmoun-Chiali, N., Richard, P., Babuty, D., Recan-Budiartha, D., Bonne, G.
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<strong>Multitissular involvement in a family with LMNA and EMD mutations: role of digenic mechanism?</strong>
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Neurology 68: 1883-1894, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17536044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17536044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17536044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000263138.57257.6a" target="_blank">Full Text</a>]
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<a id="Benedetti2007" class="mim-anchor"></a>
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Benedetti, S., Menditto, I., Degano, M., Rodolico, C., Merlini, L., D'Amico, A., Palmucci, L., Berardinelli, A., Pegoraro, E., Trevisan, C. P., Morandi, L., Moroni, I., and 15 others.
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<strong>Phenotypic clustering of lamin A/C mutations in neuromuscular patients.</strong>
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Neurology 69: 1285-1292, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000261254.87181.80" target="_blank">Full Text</a>]
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<a id="Boguslavsky2006" class="mim-anchor"></a>
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Boguslavsky, R. L., Stewart, C. L., Worman, H. J.
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<strong>Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 15: 653-663, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi480" target="_blank">Full Text</a>]
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<a id="Bonne1999" class="mim-anchor"></a>
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Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K.
|
|
<strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong>
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Nature Genet. 21: 285-288, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/6799" target="_blank">Full Text</a>]
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<a id="Brodsky2000" class="mim-anchor"></a>
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Brodsky, G. L., Muntoni, F., Miocic, S., Sinagra, G., Sewry, C., Mestroni, L.
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<strong>Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement.</strong>
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Circulation 101: 473-476, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10662742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10662742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10662742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.cir.101.5.473" target="_blank">Full Text</a>]
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<a id="Broers2004" class="mim-anchor"></a>
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Broers, J. L. V., Peeters, E. A. G., Kuijpers, H. J. H., Endert, J., Bouten, C. V. C., Oomens, C. W. J., Baaijens, F. P. T., Ramaekers, F. C. S.
|
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<strong>Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies.</strong>
|
|
Hum. Molec. Genet. 13: 2567-2580, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367494</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh295" target="_blank">Full Text</a>]
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<a id="Brown2001" class="mim-anchor"></a>
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Brown, C. A., Lanning, R. W., McKinney, K. Q., Salvino, A. R., Cherniske, E., Crowe, C. A., Darras, B. T., Gominak, S., Greenberg, C. R., Grosmann, C., Heydemann, P., Mendell, J. R., Pober, B. R., Sasaki, T., Shapiro, F., Simpson, D. A., Suchowersky, O., Spence, J. E.
|
|
<strong>Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Med. Genet. 102: 359-367, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11503164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11503164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11503164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1463" target="_blank">Full Text</a>]
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Brown, W. T.
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<strong>Personal Communication.</strong>
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Staten Island, N.Y. 1/12/2004.
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<a id="Cao2000" class="mim-anchor"></a>
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Cao, H., Hegele, R. A.
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<strong>Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.</strong>
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Hum. Molec. Genet. 9: 109-112, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.1.109" target="_blank">Full Text</a>]
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Cao, H., Hegele, R. A.
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<strong>LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).</strong>
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J. Hum. Genet. 48: 271-274, 2003.
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[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>]
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[<a href="https://doi.org/10.1007/s10038-003-0025-3" target="_blank">Full Text</a>]
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Capanni2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Capanni, C., Mattioli, E., Columbaro, M., Lucarelli, E., Parnaik, V. K., Novelli, G., Wehnert, M., Cenni, V., Maraldi, N. M., Squarzoni, S., Lattanzi, G.
|
|
<strong>Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 14: 1489-1502, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843404</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi158" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Capell2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Capell, B. C., Collins, F. S.
|
|
<strong>Human laminopathies: nuclei gone genetically awry.</strong>
|
|
Nature Rev. Genet. 7: 940-952, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17139325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17139325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17139325" 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/nrg1906" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Capell2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Capell, B. C., Erdos, M. R., Madigan, J. P., Fiordalisi, J. J., Varga, R., Conneely, K. N., Gordon, L. B., Der, C. J., Cox, A. D., Collins, F. S.
|
|
<strong>Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 12879-12884, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129833</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129833[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=16129833" 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.0506001102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Caux2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caux, F., Dubosclard, E., Lascols, O., Buendia, B., Chazouilleres, O., Cohen, A., Courvalin, J.-C., Laroche, L., Capeau, J., Vigouroux, C., Christin-Maitre, S.
|
|
<strong>A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1006-1013, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629077</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021506" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Charniot2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M.
|
|
<strong>Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.</strong>
|
|
Hum. Mutat. 21: 473-481, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.10170" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Chen2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, C.-Y., Chi, Y.-H., Mutalif, R. A., Starost, M. F., Myers, T. G., Anderson, S. A., Stewart, C. L., Jeang, K.-T.
|
|
<strong>Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.</strong>
|
|
Cell 149: 565-577, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22541428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22541428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22541428[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=22541428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2012.01.059" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Chen2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Choi2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Choi, J. C., Wu, W., Muchir, A., Iwata, S., Homma, S., Worman, H. J.
|
|
<strong>Dual specificity phosphatase 4 mediates cardiomyopathy caused by lamin A/C (LMNA) gene mutation.</strong>
|
|
J. Biol. Chem. 287: 40513-40524, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23048029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23048029</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23048029[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=23048029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M112.404541" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Coffinier2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Coffinier, C., Hudon, S. E., Farber, E. A., Chang, S. Y., Hrycyna, C. A., Young, S. G., Fong, L. G.
|
|
<strong>HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 13432-13437, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17652517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17652517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17652517[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=17652517" 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.0704212104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Cogulu2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cogulu, O., Gunduz, C., Darcan, S., Kadioglu, B., Ozkinay, F., Ozkinay, C.
|
|
<strong>Mandibuloacral dysplasia with absent breast development. (Letter)</strong>
|
|
Am. J. Med. Genet. 119A: 391-392, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12784312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12784312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12784312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.10169" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Csoka2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Csoka, A. B., Cao, H., Sammak, P. J., Constantinescu, D., Schatten, G. P., Hegele, R. A.
|
|
<strong>Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.</strong>
|
|
J. Med. Genet. 41: 304-308, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060110" 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/jmg.2003.015651" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="D'Amico2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
D'Amico, A., Haliloglu, G., Richard, P., Talim, B., Maugenre, S., Ferreiro, A., Guicheney, P., Menditto, I., Benedetti, S., Bertini, E., Bonne, G., Topaloglu, H.
|
|
<strong>Two patients with 'dropped head syndrome' due to mutations in LMNA or SEPN1 genes.</strong>
|
|
Neuromusc. Disord. 15: 521-524, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15961312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15961312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15961312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2005.03.006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="D'Apice2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
D'Apice, M. R., Tenconi, R., Mammi, I., van den Ende, J., Novelli, G.
|
|
<strong>Paternal origin of LMNA mutations in Hutchinson-Gilford progeria. (Letter)</strong>
|
|
Clin. Genet. 65: 52-54, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15032975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15032975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15032975" 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..2004.00181.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Davies2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, B. S. J., Barnes, R. H., II, Tu, Y., Ren, S., Andres, D. A., Spielmann, H. P., Lammerding, J., Wang, Y., Young, S. G., Fong, L. G.
|
|
<strong>An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.</strong>
|
|
Hum. Molec. Genet. 19: 2682-2694, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20421363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20421363</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20421363[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=20421363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq158" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="De Sandre-Giovannoli2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="De Sandre-Giovannoli2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N.
|
|
<strong>Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.</strong>
|
|
Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799477</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11799477[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=11799477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/339274" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Decaudain2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Decaudain, A., Vantyghem, M.-C., Guerci, B., Hecart, A.-C., Auclair, M., Reznik, Y., Narbonne, H., Ducluzeau, P.-H., Donadille, B., Lebbe, C., Bereziat, V., Capeau, J., Lascols, O., Vigouroux, C.
|
|
<strong>New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.</strong>
|
|
J. Clin. Endocr. Metab. 92: 4835-4844, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17711925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17711925</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17711925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2007-0654" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Eriksson2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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.
|
|
<strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature 423: 293-298, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12714972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12714972</a>, <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'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature01629" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Fatkin1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E.
|
|
<strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong>
|
|
New Eng. J. Med. 341: 1715-1724, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10580070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10580070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10580070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199912023412302" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Favreau2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Favreau, C., Higuet, D., Courvalin, J.-C., Buendia, B.
|
|
<strong>Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.</strong>
|
|
Molec. Cell. Biol. 24: 1481-1492, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749366</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14749366[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=14749366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.24.4.1481-1492.2004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Fisher1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fisher, D. Z., Chaudhary, N., Blobel, G.
|
|
<strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3462705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3462705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3462705" 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.83.17.6450" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Flier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Flier, J. S.
|
|
<strong>Pushing the envelope on lipodystrophy.</strong>
|
|
Nature Genet. 24: 103-104, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/72734" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Folker2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Folker, E. S., Ostlund, C., Luxton, G. W. G., Worman, H. J., Gundersen, G. G.
|
|
<strong>Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement.</strong>
|
|
Proc. Nat. Acad. Sci. 108: 131-136, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173262</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21173262[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=21173262" 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.1000824108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Frock2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K.
|
|
<strong>Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.</strong>
|
|
Genes Dev. 20: 486-500, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16481476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16481476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16481476[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=16481476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1364906" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Garavelli2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garavelli, L., D'Apice, M. R., Rivieri, F., Bertoli, M., Wischmeijer, A., Gelmini, C., De Nigris, V., Albertini, E., Rosato, S., Virdis, R., Bacchini, E., Dal Zotto, R., Banchini, G., Iughetti, L., Bernasconi, S., Superti-Furga, A., Novelli, G.
|
|
<strong>Mandibuloacral dysplasia type A in childhood.</strong>
|
|
Am. J. Med. Genet. 149A: 2258-2264, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19764019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19764019</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.33005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Garg2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garg, A., Cogulu, O., Ozkinay, F., Onay, H., Agarwal, A. K.
|
|
<strong>A novel homozygous ala529val LMNA mutation in Turkish patients with mandibuloacral dysplasia.</strong>
|
|
J. Clin. Endocr. Metab. 90: 5259-5264, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15998779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-2560" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Garg2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garg, A., Vinaitheerthan, M., Weatherall, P. T., Bowcock, A. M.
|
|
<strong>Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 59-65, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231979</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11231979" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.1.7121" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Genschel2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Genschel, J., Bochow, B., Kuepferling, S., Ewert, R., Hetzer, R., Lochs, H., Schmidt, H. H.-J.
|
|
<strong>A R644C mutation within lamin A extends the mutations causing dilated cardiomyopathy.</strong>
|
|
Hum. Genet. 17: 154, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11180602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1098-1004(200102)17:2<154::AID-HUMU11>3.0.CO;2-R" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Genschel2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Genschel, J., Schmidt, H. H.-J.
|
|
<strong>Mutations in the LMNA gene encoding lamin A/C.</strong>
|
|
Hum. Mutat. 16: 451-459, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11102973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11102973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11102973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1098-1004(200012)16:6<451::AID-HUMU1>3.0.CO;2-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Glynn2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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>
|
|
Hum. Molec. Genet. 14: 2959-2969, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16126733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16126733</a>, <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'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi326" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Goldman2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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.
|
|
<strong>Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184648</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[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=15184648" 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.0402943101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Gross2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 3/26/2013.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Guilly1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guilly, M. N., Bensussan, A., Bourge, J. F., Bornens, M., Courvalin, J. C.
|
|
<strong>A human T lymphoblastic cell line lacks lamins A and C.</strong>
|
|
EMBO J. 6: 3795-3799, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3501373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3501373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3501373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02715.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Gupta2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gupta, P., Bilinska, Z. T., Sylvius, N., Boudreau, E., Veinot, J. P., Labib, S., Bolongo, P. M., Hamza, A., Jackson, T., Ploski, R., Walski, M., Grzybowski, J., Walczak, E., Religa, G., Fidzianska, A., Tesson, F.
|
|
<strong>Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption.</strong>
|
|
Basic Res. Cardiol. 105: 365-377, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20127487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20127487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20127487[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=20127487" 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/s00395-010-0085-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Haque2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haque, F., Mazzeo, D., Patel, J. T., Smallwood, D. T., Ellis, J. A., Shanahan, C. M., Shackleton, S.
|
|
<strong>Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.</strong>
|
|
J. Biol. Chem. 285: 3487-3498, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19933576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19933576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19933576[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=19933576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M109.071910" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Hegele2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J., Anderson, C. M.
|
|
<strong>Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.</strong>
|
|
Physiol. Genomics 3: 39-44, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015599</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11015599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1152/physiolgenomics.2000.3.1.39" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Hegele2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Huff, M. W., Anderson, C. M.
|
|
<strong>LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.</strong>
|
|
J. Clin. Endocr. Metab. 85: 3089-3093, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10999791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.9.6768" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Hegele2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Huff, M. W., Young, T. K.
|
|
<strong>Common genomic variation in LMNA modulates indexes of obesity in Inuit.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2747-2751, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.6.7550" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Hegele2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A.
|
|
<strong>Drawing the line in progeria syndromes.</strong>
|
|
Lancet 362: 416-417, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12927424" 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)14097-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Hegele2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A.
|
|
<strong>LMNA mutation position predicts organ system involvement in laminopathies.</strong>
|
|
Clin. Genet. 68: 31-34, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952983</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952983" 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.1399-0004.2005.00447.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Hisama2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong>
|
|
Am. J. Med. Genet. 155A: 3002-3006, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[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=22065502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.34336" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Ho2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ho, C. Y., Jaalouk, D. E., Vartiainen, M. K., Lammerding, J.
|
|
<strong>Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.</strong>
|
|
Nature 497: 507-511, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23644458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23644458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23644458[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=23644458" 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/nature12105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Huang2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huang, S., Chen, L., Libina, N., Janes, J., Martin, G. M., Campisi, J., Oshima, J.
|
|
<strong>Correction of cellular phenotypes of Hutchinson-Gilford progeria cells by RNA interference.</strong>
|
|
Hum. Genet. 118: 444-450, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16208517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16208517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16208517" 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/s00439-005-0051-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Jacob2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jacob, K. N., Baptista, F., dos Santos, H. G., Oshima, J., Agarwal, A. K., Garg, A.
|
|
<strong>Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous arg133leu lamin A/C mutation.</strong>
|
|
J. Clin. Endocr. Metab. 90: 6699-6706, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16174718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-0939" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Jimenez-Escrig2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jimenez-Escrig, A., Gobernado, I., Garcia-Villanueva, M., Sanchez-Herranz, A.
|
|
<strong>Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing.</strong>
|
|
Muscle Nerve 45: 605-610, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22431096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22431096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22431096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/mus.22324" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Jung2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jung, H.-J., Coffinier, C., Choe, Y., Beigneux, A. P., Davies, B. S. J., Yang, S. H., Barnes, R. H., II, Hong, J., Sun, T., Pleasure, S. J., Young, S. G., Fong, L. G.
|
|
<strong>Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 109: E423-E431, 2012. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22308344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22308344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22308344[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=22308344" 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.1111780109" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Jung2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jung, H.-J., Tu, Y., Yang, S. H., Tatar, A., Nobumori, C., Wu, D., Young, S. G., Fong, L. G.
|
|
<strong>New Lmna knock-in mice provide a molecular mechanism for the 'segmental aging' in Hutchinson-Gilford progeria syndrome.</strong>
|
|
Hum. Molec. Genet. 23: 1506-1515, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24203701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24203701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24203701[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=24203701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddt537" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Kandert2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kandert, S., Luke, Y., Kleinhenz, T., Neumann, S., Lu, W., Jaeger, V. M., Munck, M., Wehnert, M., Muller, C. R., Zhou, Z., Noegel, A. A., Dabauvalle, M.-C., Karakesisoglou, I.
|
|
<strong>Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells.</strong>
|
|
Hum. Molec. Genet. 16: 2944-2959, 2007. Note: Erratum: Hum. Molec. Genet. 17: 468 only, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddm255" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Kane2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rhys, C., Simonson, L., Dietz, H. C., Michaelis, S.
|
|
<strong>LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.</strong>
|
|
Am. J. Med. Genet. 161A: 1599-1611, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23666920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23666920</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[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=23666920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.35971" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Kirschner2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kirschner, J., Brune, T., Wehnert, M., Denecke, J., Wasner, C., Feuer, A., Marquardt, T., Ketelsen, U.-P., Wieacker, P., Bonnemann, C. G., Korinthenberg, R.
|
|
<strong>p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.</strong>
|
|
Ann. Neurol. 57: 148-151, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15622532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15622532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15622532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Kosho2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimura, G., Kato, H., Fukushima, Y.
|
|
<strong>Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.</strong>
|
|
Am. J. Med. Genet. 143A: 2598-2603, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31983" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Krohne1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krohne, G., Benavente, R.
|
|
<strong>The nuclear lamins: a multigene family of proteins in evolution and differentiation.</strong>
|
|
Exp. Cell Res. 162: 1-10, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2415378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2415378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2415378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0014-4827(86)90421-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Lammerding2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lammerding, J., Schulze, P. C., Takahashi, T., Kozlov, S., Sullivan, T., Kamm, R. D., Stewart, C. L., Lee, R. T.
|
|
<strong>Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.</strong>
|
|
J. Clin. Invest. 113: 370-378, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14755334[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=14755334" 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/JCI19670" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Lanktree2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A.
|
|
<strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong>
|
|
Clin. Genet. 71: 183-186, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250669</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00740.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Lebel1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lebel, S., Raymond, Y.
|
|
<strong>Lamin A is not synthesized as a larger precursor polypeptide.</strong>
|
|
Biochem. Biophys. Res. Commun. 149: 417-423, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3426582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3426582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3426582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(87)90383-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Libotte2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Libotte, T., Zaim, H., Abraham, S., Padmakumar, V. C., Schneider, M., Lu, W., Munck, M., Hutchison, C., Wehnert, M., Fahrenkrog, B., Sauder, U., Aebi, U., Noegel, A. A., Karakesisoglou, I.
|
|
<strong>Lamin A/C-dependent localization of nesprin-2, a giant scaffolder at the nuclear envelope.</strong>
|
|
Molec. Biol. Cell 16: 3411-3424, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843432</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15843432[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=15843432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1091/mbc.e04-11-1009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Lin1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, F., Worman, H. J.
|
|
<strong>Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.</strong>
|
|
J. Biol. Chem. 268: 16321-16326, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8344919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8344919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8344919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Liu2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature 472: 221-225, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21346760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21346760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21346760[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=21346760" 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/nature09879" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Lloyd2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lloyd, D. J., Trembath, R. C., Shackleton, S.
|
|
<strong>A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.</strong>
|
|
Hum. Molec. Genet. 11: 769-777, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929849</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11929849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/11.7.769" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Lombardi2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lombardi, F., Gullotta, F., Columbaro, M., Filareto, A., D'Adamo, M., Vielle, A., Guglielmi, V., Nardone, A. M., Azzolini, V., Grosso, E., Lattanzi, G., D'Apice, M. R., Masala, S., Maraldi, N. M., Sbraccia, P., Novelli, G.
|
|
<strong>Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.</strong>
|
|
J. Clin. Endocr. Metab. 92: 4467-4471, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17848409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17848409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17848409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2007-0116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Machiels1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Machiels, B. M., Zorenc, A. H. G., Endert, J. M., Kuijpers, H. J. H., van Eys, G. J. J. M., Ramaekers, F. C. S., Broers, J. L. V.
|
|
<strong>An alternative splicing product of the lamin A/C gene lacks exon 10.</strong>
|
|
J. Biol. Chem. 271: 9249-9253, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8621584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.271.16.9249" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Makri2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Makri, S., Clarke, N. F., Richard, P., Maugenre, S., Demay, L., Bonne, G., Guicheney, P.
|
|
<strong>Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy.</strong>
|
|
Neuromusc. Disord. 19: 26-28, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19084400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19084400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19084400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2008.09.016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Malek2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Malek, L. A., Labib, S., Mazurkiewicz, L., Saj, M., Ploski, R., Tesson, F., Bilinska, Z. T.
|
|
<strong>A new c.1621 C-G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 56: 83-86, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21085127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21085127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21085127" 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/jhg.2010.137" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Mallampalli2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., Michaelis, S.
|
|
<strong>Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 14416-14421, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16186497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16186497</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16186497[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=16186497" 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.0503712102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="McKeon1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKeon, F. D., Kirschner, M. W., Caput, D.
|
|
<strong>Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.</strong>
|
|
Nature 319: 463-468, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3453101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3453101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3453101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/319463a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="McPherson2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F.
|
|
<strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong>
|
|
Am. J. Med. Genet. 149A: 567-572, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19283854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19283854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19283854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Mercuri2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mercuri, E., Brown, S. C., Nihoyannopoulos, P., Poulton, J., Kinali, M., Richard, P., Piercy, R. J., Messina, S., Sewry, C., Burke, M. M., McKenna, W., Bonne, G., Muntoni, F.
|
|
<strong>Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.</strong>
|
|
Muscle Nerve 31: 602-609, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15770669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15770669</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15770669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/mus.20293" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Mercuri2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mercuri, E., Poppe, M., Quinlivan, R., Messina, S., Kinali, M., Demay, L., Bourke, J., Richard, P., Sewry, C., Pike, M., Bonne, G., Muntoni, F., Bushby, K.
|
|
<strong>Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.</strong>
|
|
Arch. Neurol. 61: 690-694, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15148145" 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/archneur.61.5.690" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Meune2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meune, C., Van Berlo, J. H., Anselme, F., Bonne, G., Pinto, Y. M., Duboc, D.
|
|
<strong>Primary prevention of sudden death in patients with lamin A/C gene mutations. (Letter)</strong>
|
|
New Eng. J. Med. 354: 209-210, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16407522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMc052632" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Moller2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moller, D. V., Pham, T. T., Gustafsson, F., Hedley, P., Ersboll, M. K., Bundgaard, H., Andersen, C. B., Torp-Pedersen, C., Kober, L., Christiansen, M.
|
|
<strong>The role of lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy.</strong>
|
|
Europ. J. Heart Fail. 11: 1031-1035, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19875404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19875404</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19875404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/eurjhf/hfp134" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Morel2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morel, C. F., Thomas, M. A., Cao, H., O'Neil, C. H., Pickering, J. G., Foulkes, W. D., Hegele, R. A.
|
|
<strong>A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2.</strong>
|
|
J. Clin. Endocr. Metab. 91: 2689-2695, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16636128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16636128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16636128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-2746" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Moulson2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong>
|
|
Hum. Mutat. 28: 882-889, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17469202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17469202</a>, <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'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20536" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Mounkes2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T., Stewart, C. L.
|
|
<strong>A progeroid syndrome in mice is caused by defects in A-type lamins.</strong>
|
|
Nature 423: 298-301, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12748643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12748643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12748643" 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/nature01631" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Mounkes2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L.
|
|
<strong>Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.</strong>
|
|
Hum. Molec. Genet. 14: 2167-2180, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15972724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi221" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Muchir2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K.
|
|
<strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong>
|
|
Hum. Molec. Genet. 9: 1453-1459, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814726</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10814726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.9.1453" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Muchir2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muchir, A., Pavlidis,. P., Decostre, V., Herron, A. J., Arimura, T., Bonne, G., Worman, H. J.
|
|
<strong>Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.</strong>
|
|
J. Clin. Invest. 117: 1282-1293, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17446932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17446932</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17446932[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=17446932" 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/JCI29042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Muchir2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muchir, A., Shan, J., Bonne, G., Lehnart, S. E., Worman, H. J.
|
|
<strong>Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.</strong>
|
|
Hum. Molec. Genet. 18: 241-247, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18927124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18927124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18927124[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=18927124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddn343" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Navarro2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Navarro, C. L., Cadinanos, J., De Sandre-Giovannoli, A., Bernard, R., Courrier, S., Boccaccio, I., Boyer, A., Kleijer, W. J., Wagner, A., Giuliano, F., Beemer, F. A., Freije, J. M., Cau, P., Hennekam, R. C. M., Lopez-Otin, C., Badens, C., Levy, N.
|
|
<strong>Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors.</strong>
|
|
Hum. Molec. Genet. 14: 1503-1513, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843403</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi159" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Navarro2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong>
|
|
Hum. Molec. Genet. 13: 2493-2503, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15317753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Nguyen2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nguyen, D., Leistritz, D. F., Turner, L., MacGregor, D., Ohson, K., Dancey, P., Martin, G. M., Oshima, J.
|
|
<strong>Collagen expression in fibroblasts with a novel LMNA mutation.</strong>
|
|
Biochem. Biophys. Res. Commun. 352: 603-608, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17150192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17150192</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17150192[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=17150192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.bbrc.2006.11.070" target="_blank">Full Text</a>]
|
|
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</p>
|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Novelli2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M. R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G.
|
|
<strong>Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.</strong>
|
|
Am. J. Hum. Genet. 71: 426-431, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075506</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12075506[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=12075506" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/341908" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Pan2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pan, Y., Garg, A., Agarwal, A. K.
|
|
<strong>Mislocalization of prelamin A Tyr646Phe mutant to the nuclear pore complex in human embryonic kidney 293 cells.</strong>
|
|
Biochem. Biophys. Res. Commun. 355: 78-84, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17291448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17291448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17291448[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=17291448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.bbrc.2007.01.116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Plasilova2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plasilova, M., Chattopadhyay, C., Pal, P., Schaub, N. A., Buechner, S. A., Mueller, H., Miny, P., Ghosh, A., Heinimann, K.
|
|
<strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong>
|
|
J. Med. Genet. 41: 609-614, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15286156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15286156</a>, <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'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Quijano-Roy2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others.
|
|
<strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong>
|
|
Ann. Neurol. 64: 177-186, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.21417" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Raffaele di Barletta2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raffaele di Barletta, M., Ricci, E., Galluzzi, G., Tonali, P., Mora, M., Morandi, L., Romorini, A., Voit, T., Orstavik, K. H., Merlini, L., Trevisan, C., Biancalana, V., Housmanowa-Petrusewicz, I., Bione, S., Ricotti, R., Schwartz, K., Bonne, G., Toniolo, D.
|
|
<strong>Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 66: 1407-1412, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739764[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=10739764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302869" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Rankin2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rankin, J., Auer-Grumbach, M., Bagg, W., Colclough, K., Duong, N. T., Fenton-May, J., Hattersley, A., Hudson, J., Jardine, P., Josifova, D., Longman, C., McWilliam, R., Owen, K., Walker, M., Wehnert, M., Ellard, S.
|
|
<strong>Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.</strong>
|
|
Am. J. Med. Genet. 146A: 1530-1542, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18478590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.32331" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Reddel2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reddel, C. J., Weiss, A. S.
|
|
<strong>Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.</strong>
|
|
J. Med. Genet. 41: 715-717, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342704" 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/jmg.2004.019323" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Renou2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Renou, L., Stora, S., Yaou, R. B., Volk, M., Sinkovec, M., Demay, L., Richard, P., Peterlin, B., Bonne, G.
|
|
<strong>Heart-hand syndrome of Slovenian type: a new kind of laminopathy. (Letter)</strong>
|
|
J. Med. Genet. 45: 666-671, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18611980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18611980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18611980" 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/jmg.2008.060020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Rodriguez2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rodriguez, S., Coppede, F., Sagelius, H., Eriksson, M.
|
|
<strong>Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging.</strong>
|
|
Europ. J. Hum. Genet. 17: 928-937, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19172989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19172989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19172989[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=19172989" 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.2008.270" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Rudnik-Schoneborn2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Botzenhart, E., Eggermann, T., Senderek, J., Schoser, B. G. H., Schroder, R., Wehnert, M., Wirth, B., Zerres, K.
|
|
<strong>Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.</strong>
|
|
Neurogenetics 8: 137-142, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17136397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17136397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17136397" 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/s10048-006-0070-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Scaffidi2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature Med. 11: 440-445, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15750600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15750600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15750600[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=15750600" 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/nm1204" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
<a id="Scaffidi2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Lamin A-dependent nuclear defects in human aging.</strong>
|
|
Science 312: 1059-1063, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16645051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16645051</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16645051[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=16645051" 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.1127168" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
<a id="Scaffidi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.</strong>
|
|
Nature Cell Biol. 10: 452-459, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18311132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18311132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18311132[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=18311132" 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/ncb1708" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Scharner2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scharner, J., Brown, C. A., Bower, M., Iannaccone, S. T., Khatri, I. A., Escolar, D., Gordon, E., Felice, K., Crowe, C. A., Grosmann, C., Meriggioli, M. N., Asamoah, A., Gordon, O., Gnocchi, V. F., Ellis, J. A., Mendell, J. R., Zammit, P. S.
|
|
<strong>Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.</strong>
|
|
Hum. Mutat. 32: 152-167, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20848652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20848652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20848652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.21361" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Schmidt2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schmidt, H. H.-J., Genschel, J., Baier, P., Schmidt, M., Ockenga, J., Tietge, U. J. F., Propsting, M., Buttner, C., Manns, M. P., Lochs, H., Brabant, G.
|
|
<strong>Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2289-2295, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11344241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11344241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11344241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.5.7500" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Schreiber2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schreiber, K. H., Kennedy, B. K.
|
|
<strong>When lamins go bad: nuclear structure and disease.</strong>
|
|
Cell 152: 1365-1375, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23498943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23498943</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23498943[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=23498943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2013.02.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Sebillon2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M.
|
|
<strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong>
|
|
J. Med. Genet. 40: 560-567, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920062" 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/jmg.40.8.560" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="110" class="mim-anchor"></a>
|
|
<a id="Shackleton2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C.
|
|
<strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong>
|
|
Nature Genet. 24: 153-156, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655060</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/72807" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Shen2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shen, J. J., Brown, C. A., Lupski, J. R., Potocki, L.
|
|
<strong>Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C.</strong>
|
|
J. Med. Genet. 40: 854-857, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627682</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14627682" 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/jmg.40.11.854" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Shumaker2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shumaker, D. K., Dechat, T., Kohlmaier, A., Adam, S. A., Bozovsky, M. R., Erdos, M. R., Eriksson, M., Goldman, A. E., Khuon, S., Collins, F. S., Jenuwein, T., Goldman, R. D.
|
|
<strong>Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 8703-8708, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738054</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16738054[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=16738054" 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.0602569103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Simha2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Simha, V., Agarwal, A. K., Oral, E. A., Fryns, J.-P., Garg, A.
|
|
<strong>Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2821-2824, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788894</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021575" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="114" class="mim-anchor"></a>
|
|
<a id="Simon2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L.
|
|
<strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong>
|
|
Molec. Biol. Cell 24: 342-350, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23243001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23243001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23243001[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=23243001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1091/mbc.E12-07-0527" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="Sinensky1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sinensky, M., Fantle, K., Trujillo, M., McLain, T., Kupfer, A., Dalton, M.
|
|
<strong>The processing pathway of prelamin A.</strong>
|
|
J. Cell Sci. 107: 61-67, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8175923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8175923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8175923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1242/jcs.107.1.61" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="116" class="mim-anchor"></a>
|
|
<a id="Sinkovec2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sinkovec, M., Petrovic, D., Volk, M., Peterlin, B.
|
|
<strong>Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly: a new type of heart-hand syndrome?</strong>
|
|
Clin. Genet. 68: 155-160, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996213</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15996213" 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.1399-0004.2005.00476.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Speckman2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M.
|
|
<strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong>
|
|
Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10739751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10739751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10739751[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=10739751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302836" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Straub2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Straub, V., Murphy, A., Udd, B.
|
|
<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
|
|
Neuromusc. Disord. 28: 702-710, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Taylor2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group.
|
|
<strong>Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.</strong>
|
|
J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12628721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12628721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12628721" 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/s0735-1097(02)02954-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="120" class="mim-anchor"></a>
|
|
<a id="Thomasson2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomasson, R., Vignier, N., Peccate, C., Mougenot, N., Noirez, P., Muchir, A.
|
|
<strong>Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.</strong>
|
|
Hum. Molec. Genet. 28: 2237-2244, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31220270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31220270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31220270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddz056" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="121" class="mim-anchor"></a>
|
|
<a id="Toth2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Toth, J. I., Yang, S. H., Qiao, X., Beigneux, A. P., Gelb, M. H., Moulson, C. L., Miner, J. H., Young, S. G., Fong, L. G.
|
|
<strong>Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 12873-12878, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16129834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16129834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16129834[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=16129834" 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.0505767102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="122" class="mim-anchor"></a>
|
|
<a id="Vadrot2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vadrot, N., Duband-Goulet, I., Cabet, E., Attanda, W., Barateau, A., Vicart, P., Gerbal, F., Briand, N., Vigouroux, C., Oldenburg, A. R., Lund, E. G., Collas, P., Buendia, B.
|
|
<strong>The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 24: 2096-2109, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25524705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25524705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25524705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddu728" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="123" class="mim-anchor"></a>
|
|
<a id="Van Berlo2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Berlo, J. H., Voncken, J. W., Kubben, N., Broers, J. L. V., Duisters, R., van Leeuwen, R. E. W., Crijns, H. J. G. M., Ramaekers, F. C. S., Hutchison, C. J., Pinto, Y. M.
|
|
<strong>A-type lamins are essential for TGF-beta-1 induced PP2A to dephosphorylate transcription factors.</strong>
|
|
Hum. Molec. Genet. 14: 2839-2849, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi316" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="124" class="mim-anchor"></a>
|
|
<a id="van der Kooi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M.
|
|
<strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong>
|
|
Neurology 59: 620-623, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12196663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.59.4.620" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="125" class="mim-anchor"></a>
|
|
<a id="van der Kooi1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., Ledderhof, T. M., de Voogt, W. G., Res, J. C. J., Bouwsma, G., Troost, D., Busch, H. F. M., Becker, A. E., de Visser, M.
|
|
<strong>A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement.</strong>
|
|
Ann. Neurol. 39: 636-642, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8619549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.410390513" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="126" class="mim-anchor"></a>
|
|
<a id="van der Kooi1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., van Meegen, M., Ledderhof, T. M., McNally, E. M., de Visser, M., Bolhuis, P. A.
|
|
<strong>Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21.</strong>
|
|
Am. J. Hum. Genet. 60: 891-895, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="127" class="mim-anchor"></a>
|
|
<a id="van Engelen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van Engelen, B. G. M., Muchir, A., Hutchison, C. J., van der Kooi, A. J., Bonne, G., Lammens, M.
|
|
<strong>The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene.</strong>
|
|
Neurology 64: 374-376, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15668447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.WNL.0000149763.15180.00" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="128" class="mim-anchor"></a>
|
|
<a id="Van Esch2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Agarwal, A. K., Debeer, P., Fryns, J.-P., Garg, A.
|
|
<strong>A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.</strong>
|
|
J. Clin. Endocr. Metab. 91: 517-521, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278265</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-1297" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="129" class="mim-anchor"></a>
|
|
<a id="Vantyghem2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vantyghem, M. C., Pigny, P., Maurage, C. A., Rouaix-Emery, N., Stojkovic, T., Cuisset, J. M., Millaire, A., Lascols, O., Vermersch, P., Wemeau, J. L., Capeau, J., Vigouroux, C.
|
|
<strong>Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5337-5346, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531479</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-031658" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="130" class="mim-anchor"></a>
|
|
<a id="Varga2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 3250-3255, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16492728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16492728</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16492728[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=16492728" 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.0600012103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="131" class="mim-anchor"></a>
|
|
<a id="Vigouroux2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vigouroux, C., Auclair, M., Dubosclard, E., Pouchelet, M., Capeau, J., Courvalin, J.-C., Buendia, B.
|
|
<strong>Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.</strong>
|
|
J. Cell Sci. 114: 4459-4468, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11792811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11792811</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11792811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1242/jcs.114.24.4459" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="132" class="mim-anchor"></a>
|
|
<a id="Vigouroux2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vigouroux, C., Caux, F. Capeau, J., Christin-Maitre, S., Cohen, A.
|
|
<strong>LMNA mutations in atypical Werner's syndrome. (Letter)</strong>
|
|
Lancet 362: 1585 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14615128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14615128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14615128" 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)14760-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="133" class="mim-anchor"></a>
|
|
<a id="Wang2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, Y., Shilagardi, K., Hsu, T., Odinammadu, K. O., Maruyama, T., Wu, W., Lin, C. S., Damoci, C. B., Spear, E. D., Shin, J. Y., Hsu, W., Michaelis, S., Worman, H. J.
|
|
<strong>Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 119: e2118695119, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35197292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35197292</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35197292[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=35197292" 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.2118695119" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="134" class="mim-anchor"></a>
|
|
<a id="Weber1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weber, K., Plessmann, U., Traub, P.
|
|
<strong>Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina.</strong>
|
|
FEBS Lett. 257: 411-414, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2583287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2583287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2583287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0014-5793(89)81584-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="135" class="mim-anchor"></a>
|
|
<a id="Wiltshire2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wiltshire, K. M., Hegele, R. A., Innes, A. M., Brownell, A. K. W.
|
|
<strong>Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.</strong>
|
|
Neuromusc. Disord. 23: 265-268, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23313286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23313286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23313286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2012.11.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="136" class="mim-anchor"></a>
|
|
<a id="Worman2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Worman, H. J., Bonne, G.
|
|
<strong>'Laminopathies': a wide spectrum of human diseases.</strong>
|
|
Exp. Cell Res. 313: 2121-2133, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17467691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17467691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17467691[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=17467691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.yexcr.2007.03.028" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="137" class="mim-anchor"></a>
|
|
<a id="Wuyts2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wuyts, W., Biervliet, M., Reyniers, E., D'Apice, M. R., Novelli, G., Storm, K.
|
|
<strong>Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.</strong>
|
|
Am. J. Med. Genet. 135A: 66-68, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15793835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15793835</a>, <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'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30663" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="138" class="mim-anchor"></a>
|
|
<a id="Wydner1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B.
|
|
<strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong>
|
|
Genomics 32: 474-478, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0146" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="139" class="mim-anchor"></a>
|
|
<a id="Yang2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, S. H., Andres, D. A., Spielmann, H. P., Young, S. G., Fong, L. G.
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<strong>Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated.</strong>
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J. Clin. Invest. 118: 3291-3300, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18769635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18769635</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18769635[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=18769635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI35876" target="_blank">Full Text</a>]
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<a id="Yang2005" class="mim-anchor"></a>
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Yang, S. H., Bergo, M. O., Toth, J. I., Qiao, X., Hu, Y., Sandoval, S., Meta, M., Bendale, P., Gelb, M. H., Young, S. G., Fong, L. G.
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<strong>Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.</strong>
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Proc. Nat. Acad. Sci. 102: 10291-10296, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16014412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16014412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16014412[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=16014412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0504641102" target="_blank">Full Text</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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<strong>A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.</strong>
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J. Clin. Invest. 116: 2115-2121, 2006.
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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>]
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[<a href="https://doi.org/10.1172/JCI28968" target="_blank">Full Text</a>]
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Zaragoza, M. V., Hakim, S. A., Hoang, V., Elliott, A. M.
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<strong>Heart-hand syndrome IV: a second family with LMNA-related cardiomyopathy and brachydactyly. (Letter)</strong>
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Clin. Genet. 91: 499-500, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27723096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27723096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27723096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12870" target="_blank">Full Text</a>]
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<a id="Zirn2008" class="mim-anchor"></a>
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Zirn, B., Kress, W., Grimm, T., Berthold, L. D., Neubauer, B., Kuchelmeister, K., Muller, U., Hahn, A.
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<strong>Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.</strong>
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Am. J. Med. Genet. 146A: 1049-1054, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32259" target="_blank">Full Text</a>]
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Bao Lige - updated : 12/01/2022
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Bao Lige - updated : 02/08/2022<br>Carol A. Bocchini - updated : 11/19/2018<br>Patricia A. Hartz - updated : 10/28/2016<br>Cassandra L. Kniffin - updated : 10/27/2015<br>Cassandra L. Kniffin - updated : 9/4/2015<br>Cassandra L. Kniffin - updated : 8/13/2015<br>Patricia A. Hartz - updated : 11/25/2014<br>Patricia A. Hartz - updated : 8/6/2014<br>Marla J. F. O'Neill - updated : 4/30/2014<br>Carol A. Bocchini - updated : 2/18/2014<br>George E. Tiller - updated : 9/10/2013<br>George E. Tiller - updated : 8/23/2013<br>Ada Hamosh - updated : 7/11/2013<br>Patricia A. Hartz - updated : 6/10/2013<br>Matthew B. Gross - updated : 3/26/2013<br>Cassandra L. Kniffin - updated : 10/3/2012<br>Ada Hamosh - updated : 6/7/2011<br>Cassandra L. Kniffin - updated : 2/14/2011<br>Marla J. F. O'Neill - updated : 10/19/2010<br>Cassandra L. Kniffin - updated : 10/13/2010<br>Paul J. Converse - updated : 9/20/2010<br>Patricia A. Hartz - updated : 8/10/2010<br>Patricia A. Hartz - updated : 7/27/2010<br>Cassandra L. Kniffin - updated : 4/7/2010<br>Nara Sobreira - updated : 1/8/2010<br>Cassandra L. Kniffin - updated : 1/5/2010<br>Cassandra L. Kniffin - updated : 11/2/2009<br>George E. Tiller - updated : 8/3/2009<br>Cassandra L. Kniffin - updated : 7/9/2009<br>Patricia A. Hartz - updated : 6/30/2009<br>George E. Tiller - updated : 5/13/2009<br>George E. Tiller - updated : 4/22/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 3/5/2009<br>Marla J. F. O'Neill - updated : 2/19/2009<br>George E. Tiller - updated : 11/19/2008<br>Paul J. Converse - updated : 10/27/2008<br>John A. Phillips, III - updated : 9/23/2008<br>John A. Phillips, III - updated : 9/23/2008<br>George E. Tiller - updated : 6/5/2008<br>Cassandra L. Kniffin - updated : 1/30/2008<br>Marla J. F. O'Neill - updated : 11/21/2007<br>Cassandra L. Kniffin - updated : 11/7/2007<br>George E. Tiller - updated : 10/31/2007<br>Cassandra L. Kniffin - updated : 10/16/2007<br>John A. Phillips, III - updated : 7/17/2007<br>George E. Tiller - updated : 6/13/2007<br>Cassandra L. Kniffin - updated : 5/2/2007<br>John A. Phillips, III - updated : 4/9/2007<br>John A. Phillips, III - updated : 3/22/2007<br>Marla J. F. O'Neill - updated : 3/8/2007<br>Ada Hamosh - updated : 8/1/2006<br>Cassandra L. Kniffin - updated : 6/26/2006<br>Patricia A. Hartz - updated : 3/28/2006<br>Marla J. F. O'Neill - updated : 3/22/2006<br>Marla J. F. O'Neill - updated : 2/15/2006<br>Victor A. McKusick - updated : 2/1/2006<br>Marla J. F. O'Neill - updated : 7/5/2005<br>Marla J. F. O'Neill - updated : 6/1/2005<br>George E. Tiller - updated : 5/19/2005<br>Victor A. McKusick - updated : 5/11/2005<br>John A. Phillips, III - updated : 4/13/2005<br>Victor A. McKusick - updated : 3/15/2005<br>Victor A. McKusick - updated : 2/22/2005<br>Victor A. McKusick - updated : 2/17/2005<br>Marla J. F. O'Neill - updated : 11/3/2004<br>Patricia A. Hartz - updated : 10/27/2004<br>Victor A. McKusick - updated : 10/12/2004<br>Cassandra L. Kniffin - reorganized : 5/3/2004<br>Cassandra L. Kniffin - updated : 4/15/2004<br>Victor A. McKusick - updated : 2/25/2004<br>Patricia A. Hartz - updated : 2/17/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 1/20/2004<br>Cassandra L. Kniffin - updated : 1/6/2004<br>Victor A. McKusick - updated : 10/22/2003<br>Victor A. McKusick - updated : 10/1/2003<br>John A. Phillips, III - updated : 8/25/2003<br>John A. Phillips, III - updated : 8/25/2003<br>Victor A. McKusick - updated : 6/11/2003<br>Ada Hamosh - updated : 5/28/2003<br>Ada Hamosh - updated : 4/29/2003<br>Ada Hamosh - updated : 4/23/2003<br>Ada Hamosh - updated : 4/16/2003<br>Cassandra L. Kniffin - updated : 12/16/2002<br>George E. Tiller - updated : 10/28/2002<br>Victor A. McKusick - updated : 8/16/2002<br>Victor A. McKusick - updated : 3/21/2002<br>John A. Phillips, III - updated : 11/6/2001<br>John A. Phillips, III - updated : 10/4/2001<br>John A. Phillips, III - updated : 7/16/2001<br>John A. Phillips, III - updated : 3/16/2001<br>Victor A. McKusick - updated : 1/2/2001<br>George E. Tiller - updated : 8/16/2000<br>Victor A. McKusick - updated : 7/20/2000<br>Victor A. McKusick - updated : 4/13/2000<br>Paul Brennan - updated : 4/10/2000<br>Victor A. McKusick - updated : 1/28/2000<br>Victor A. McKusick - updated : 12/14/1999<br>Victor A. McKusick - updated : 12/3/1999<br>Victor A. McKusick - updated : 2/23/1999<br>Alan F. Scott - updated : 4/22/1996
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Victor A. McKusick : 1/5/1988
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carol : 01/11/2023
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mgross : 12/01/2022<br>alopez : 11/17/2022<br>carol : 03/14/2022<br>carol : 03/11/2022<br>mgross : 02/08/2022<br>alopez : 02/12/2020<br>carol : 11/19/2018<br>carol : 10/05/2018<br>carol : 09/26/2018<br>carol : 09/25/2018<br>carol : 10/29/2016<br>alopez : 10/28/2016<br>alopez : 08/04/2016<br>carol : 10/29/2015<br>ckniffin : 10/27/2015<br>carol : 9/9/2015<br>ckniffin : 9/4/2015<br>carol : 8/18/2015<br>alopez : 8/14/2015<br>mcolton : 8/13/2015<br>ckniffin : 8/13/2015<br>mgross : 11/26/2014<br>mcolton : 11/25/2014<br>mgross : 10/14/2014<br>mgross : 10/14/2014<br>mcolton : 8/6/2014<br>carol : 6/15/2014<br>carol : 5/1/2014<br>mcolton : 4/30/2014<br>carol : 2/18/2014<br>carol : 9/18/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 8/23/2013<br>alopez : 7/11/2013<br>mgross : 6/10/2013<br>mgross : 6/10/2013<br>alopez : 6/10/2013<br>mgross : 3/26/2013<br>carol : 10/17/2012<br>carol : 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2/24/2009<br>wwang : 2/23/2009<br>wwang : 2/23/2009<br>terry : 2/19/2009<br>wwang : 11/19/2008<br>mgross : 10/27/2008<br>alopez : 9/23/2008<br>alopez : 9/23/2008<br>alopez : 9/23/2008<br>wwang : 6/11/2008<br>terry : 6/5/2008<br>wwang : 2/1/2008<br>ckniffin : 1/30/2008<br>carol : 11/26/2007<br>carol : 11/26/2007<br>terry : 11/21/2007<br>wwang : 11/20/2007<br>ckniffin : 11/7/2007<br>alopez : 11/6/2007<br>terry : 10/31/2007<br>wwang : 10/25/2007<br>ckniffin : 10/16/2007<br>terry : 9/20/2007<br>alopez : 7/17/2007<br>wwang : 6/14/2007<br>terry : 6/13/2007<br>wwang : 6/8/2007<br>wwang : 5/11/2007<br>ckniffin : 5/2/2007<br>carol : 4/9/2007<br>alopez : 3/22/2007<br>wwang : 3/12/2007<br>terry : 3/8/2007<br>wwang : 8/9/2006<br>alopez : 8/3/2006<br>terry : 8/1/2006<br>wwang : 7/5/2006<br>ckniffin : 6/26/2006<br>wwang : 3/29/2006<br>terry : 3/28/2006<br>wwang : 3/22/2006<br>wwang : 2/23/2006<br>terry : 2/15/2006<br>alopez : 2/15/2006<br>terry : 2/3/2006<br>terry : 2/1/2006<br>terry : 10/12/2005<br>wwang : 7/8/2005<br>terry : 7/5/2005<br>alopez : 6/13/2005<br>wwang : 6/8/2005<br>wwang : 6/1/2005<br>tkritzer : 5/25/2005<br>terry : 5/19/2005<br>wwang : 5/18/2005<br>wwang : 5/11/2005<br>wwang : 5/11/2005<br>wwang : 4/13/2005<br>wwang : 3/22/2005<br>wwang : 3/18/2005<br>terry : 3/16/2005<br>terry : 3/15/2005<br>carol : 3/8/2005<br>carol : 3/8/2005<br>carol : 3/8/2005<br>wwang : 3/7/2005<br>terry : 2/22/2005<br>terry : 2/21/2005<br>terry : 2/17/2005<br>joanna : 2/9/2005<br>carol : 12/8/2004<br>tkritzer : 12/7/2004<br>tkritzer : 11/4/2004<br>terry : 11/3/2004<br>mgross : 10/27/2004<br>tkritzer : 10/15/2004<br>terry : 10/12/2004<br>terry : 6/28/2004<br>tkritzer : 5/10/2004<br>carol : 5/4/2004<br>carol : 5/3/2004<br>ckniffin : 4/29/2004<br>ckniffin : 4/28/2004<br>ckniffin : 4/27/2004<br>ckniffin : 4/27/2004<br>ckniffin : 4/15/2004<br>cwells : 3/4/2004<br>tkritzer : 2/26/2004<br>terry : 2/25/2004<br>cwells : 2/23/2004<br>terry : 2/17/2004<br>cwells : 2/16/2004<br>terry : 2/9/2004<br>carol : 1/21/2004<br>terry : 1/20/2004<br>tkritzer : 1/13/2004<br>ckniffin : 1/6/2004<br>terry : 11/11/2003<br>tkritzer : 10/24/2003<br>alopez : 10/22/2003<br>tkritzer : 10/22/2003<br>tkritzer : 10/7/2003<br>tkritzer : 10/1/2003<br>alopez : 8/25/2003<br>alopez : 8/25/2003<br>alopez : 7/7/2003<br>tkritzer : 6/25/2003<br>tkritzer : 6/24/2003<br>terry : 6/11/2003<br>alopez : 5/28/2003<br>alopez : 5/28/2003<br>terry : 5/28/2003<br>alopez : 5/9/2003<br>alopez : 4/30/2003<br>terry : 4/29/2003<br>alopez : 4/25/2003<br>alopez : 4/23/2003<br>joanna : 4/23/2003<br>alopez : 4/16/2003<br>terry : 4/16/2003<br>ckniffin : 4/10/2003<br>tkritzer : 2/28/2003<br>carol : 1/3/2003<br>carol : 1/3/2003<br>tkritzer : 12/23/2002<br>ckniffin : 12/16/2002<br>cwells : 11/19/2002<br>terry : 11/15/2002<br>cwells : 10/28/2002<br>tkritzer : 8/23/2002<br>tkritzer : 8/22/2002<br>terry : 8/16/2002<br>alopez : 4/19/2002<br>carol : 4/2/2002<br>alopez : 3/27/2002<br>terry : 3/21/2002<br>mcapotos : 12/21/2001<br>alopez : 11/6/2001<br>cwells : 10/8/2001<br>cwells : 10/4/2001<br>cwells : 7/20/2001<br>cwells : 7/16/2001<br>alopez : 3/16/2001<br>cwells : 1/11/2001<br>terry : 1/2/2001<br>alopez : 8/16/2000<br>mcapotos : 7/24/2000<br>mcapotos : 7/20/2000<br>mcapotos : 6/30/2000<br>carol : 5/9/2000<br>carol : 5/9/2000<br>alopez : 5/8/2000<br>terry : 4/13/2000<br>terry : 4/13/2000<br>alopez : 4/10/2000<br>alopez : 2/1/2000<br>terry : 1/28/2000<br>alopez : 12/14/1999<br>carol : 12/14/1999<br>mgross : 12/3/1999<br>terry : 12/3/1999<br>alopez : 3/1/1999<br>alopez : 3/1/1999<br>alopez : 2/26/1999<br>terry : 2/23/1999<br>terry : 4/22/1996<br>mark : 4/22/1996<br>mark : 12/7/1995<br>carol : 10/1/1993<br>carol : 8/14/1992<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 2/3/1990<br>ddp : 10/27/1989
|
|
</span>
|
|
</div>
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|
</div>
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|
</div>
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</div>
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</div>
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</div>
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|
<div class="container visible-print-block">
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<div class="row">
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|
<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
|
<strong>*</strong> 150330
|
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</span>
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</h3>
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
|
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|
|
LAMIN A/C; LMNA
|
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</span>
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
|
|
Other entities represented in this entry:
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|
</span>
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</p>
|
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</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
|
LAMIN A, INCLUDED
|
|
</span>
|
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</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
LAMIN C, INCLUDED; LMNC, INCLUDED<br />
|
|
PRELAMIN A, INCLUDED<br />
|
|
PROGERIN, INCLUDED
|
|
</span>
|
|
</div>
|
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|
|
</div>
|
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<div>
|
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<br />
|
|
</div>
|
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|
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: LMNA</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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|
|
<strong>SNOMEDCT:</strong> 1003431005, 1010712009, 238870004, 53043001, 715439000, 719451006, 721014007, 725048002, 771272007;
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<strong>ICD10CM:</strong> E34.8;
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
|
Cytogenetic location: 1q22
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|
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:156,082,573-156,140,081 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
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|
</p>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed 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>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="11">
|
|
<span class="mim-font">
|
|
1q22
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1A
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
115200
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, type 2B1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
605588
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emery-Dreifuss muscular dystrophy 2, autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
181350
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emery-Dreifuss muscular dystrophy 3, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616516
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Heart-hand syndrome, Slovenian type
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610140
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hutchinson-Gilford progeria
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176670
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Lipodystrophy, familial partial, type 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
151660
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Malouf syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
212112
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mandibuloacral dysplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
248370
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, congenital
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613205
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Restrictive dermopathy 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619793
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The LMNA gene encodes lamin A and lamin C. Lamins are structural protein components of the nuclear lamina, a protein network underlying the inner nuclear membrane that determines nuclear shape and size. The lamins constitute a class of intermediate filaments. Three types of lamins, A, B (see LMNB1; 150340), and C, have been described in mammalian cells (Fisher et al., 1986). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
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<p>By screening human fibroblast and hepatoma cDNA libraries, Fisher et al. (1986) isolated cDNAs corresponding to lamin A and lamin C. The lamin A and C proteins are predicted to have molecular masses of 74 kD and 65 kD, respectively. Fisher et al. (1986) and McKeon et al. (1986) found that the deduced amino acid sequences from cDNA clones of human lamin A and C are identical for the first 566 amino acids, but that lamin A contains an extra 98 amino acids (corresponding to approximately 9 kD) at the C terminus. Lamin C has 6 unique C-terminal amino acids. Both lamins A and C contain a 360-residue alpha-helical domain with homology to a corresponding alpha-helical rod domain that is the structural hallmark of all intermediate filament proteins. Fisher et al. (1986) and McKeon et al. (1986) concluded that lamin A and lamin C arise by alternative splicing from the same gene. </p><p>Guilly et al. (1987) detected a 3-kb lamin A mRNA and a 2.1-kb lamin C mRNA in epithelial HeLa cells, but not in T lymphoblasts. Lamin B was the only lamin present in T lymphoblasts. Guilly et al. (1987) noted that the transport of newly synthesized proteins from the cytoplasm into the nucleus differs from the transport of proteins into other organelles, such as mitochondria, in that sequences are not cleaved and remain a permanent feature of the mature polypeptide. Lamin A appears to be an exception to this rule. </p><p>Weber et al. (1989) showed that lamin A is synthesized as a precursor molecule called prelamin A. Maturation of lamin A involves the removal of 18 residues from the C terminus, which is accomplished by isoprenylation and farnesylation involving a C-terminal CAAX (cysteine-aliphatic-aliphatic-any amino acid) box (Sinensky et al., 1994). </p><p>By RT-PCR analysis of several human cell lines, Machiels et al. (1996) identified an LMNA splice variant, lamin A-delta-10, that lacks exon 10. The predicted protein lacks 30 amino acids in the lamin A tail, which in full-length lamin A contains an aspartic acid- and glutamine-rich stretch, followed by 4 consecutive histidines. Variable lamin A-delta-10 expression was detected in all cell lines and tissues examined. The ratio of lamin A to lamin A-delta-10 varied among samples. Western blot analysis of a 2-dimensional gel revealed a lamin A doublet with an apparent molecular mass of approximately 70 kD and a second, more basic protein of approximately 65 kD. </p><p>Using Western blot analysis, Jung et al. (2012) found that lamins A and C were highly expressed in mouse heart, liver, and kidney, with lamin A showing slightly higher expression than lamin C. In contrast, expression of lamin A was much lower than that of lamin C in cerebral cortex and cerebellum. Immunohistochemical analysis revealed that only vascular and meningeal cells in mouse brain expressed significant lamin A, whereas lamin C showed widespread expression in brain. Northern blot analysis and quantitative RT-PCR confirmed high expression of lamin C, but not lamin A, in mouse cerebral cortex and cerebellum. </p><p>Simon et al. (2013) stated that prelamin A is C-terminally farnesylated and carboxymethylated, then proteolytically cleaved after tyr646 (Y646) to generate mature lamin A. Mature lamin A can be further modified by acetylation, phosphorylation, or addition of N-acetylglucosamine, and the rod domain can be sumoylated by SUMO2 (603042). Simon et al. (2013) found that the tail domain of mature lamin A, comprising residues 385 to 646, was modified by SUMO1 (601912). </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</h4>
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<p>Lin and Worman (1993) demonstrated that the coding region of the lamin A/C gene spans approximately 24 kb and contains 12 exons. Alternative splicing within exon 10 gives rise to 2 different mRNAs that code for prelamin A and lamin C. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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<p>Wydner et al. (1996) mapped the LMNA gene to chromosome 1q21.2-q21.3 by fluorescence in situ hybridization. </p><p>Gross (2013) mapped the LMNA gene to chromosome 1q22 based on an alignment of the LMNA sequence (GenBank AY847595) with the genomic sequence (GRCh37).</p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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<p>Lloyd et al. (2002) identified proteins interacting with the C-terminal domain of lamin A by screening a mouse 3T3-L1 adipocyte library in a yeast 2-hybrid interaction screen. Using this approach, the adipocyte differentiation factor SREBP1 (184756) was identified as a novel lamin A interactor. In vitro glutathione S-transferase pull-down and in vivo coimmunoprecipitation studies confirmed an interaction between lamin A and both SREBP1a and 1c. A binding site for lamin A was identified in the N-terminal transcription factor domain of SREBP1, between residues 227 and 487. The binding of lamin A to SREBP1 was noticeably reduced by FPLD mutations. The authors speculated that fat loss seen in laminopathies may be caused in part by reduced binding of the adipocyte differentiation factor SREBP1 to lamin A. </p><p>Favreau et al. (2004) analyzed myoblast-to-myotube differentiation in a mouse myogenic cell line overexpressing wildtype or mutant human lamin A. In contrast to clones overexpressing wildtype lamin A, those expressing lamin A with the R453W mutation (150330.0002) differentiated poorly or not at all, did not exit the cell cycle properly, and were extensively committed to apoptosis. Clones expressing the R482W mutation (150330.0011) differentiated normally. Favreau et al. (2004) concluded that lamin A mutated at arginine-453 fails to build a functional scaffold and/or fails to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes. </p><p>Using a novel technique to measure nuclear deformation in response to biaxial strain applied to cells, Lammerding et al. (2004) found that Lmna -/- cells showed increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain compared to wildtype cells. In addition, activity of nuclear factor-kappa-B (NFKB; 164011), a mechanical stress-responsive transcription factor that can act as an antiapoptotic signal, was impaired in the Lmna -/- cells. The findings suggested that lamin A/C deficiency is associated with both defective nuclear mechanics and impaired transcriptional activation. </p><p>Broers et al. (2004) used a cell compression device to compare wildtype and Lmna-knockout mouse embryonic fibroblasts, and found that Lmna-null cells showed significantly decreased mechanical stiffness and significantly lower bursting force. Partial rescue of the phenotype by transfection with either lamin A or lamin C prevented gross nuclear disruption, but was unable to fully restore mechanical stiffness. Confocal microscopy revealed that the nuclei of Lmna-null cells exhibited an isotropic deformation upon indentation, despite an anisotropic deformation of the cell as a whole. This nuclear behavior suggested a loss of interaction of the disturbed nucleus with the surrounding cytoskeleton. Actin (102610)-, vimentin (193060)-, and tubulin (191110)-based filaments showed disturbed interaction in Lmna-null cells. Broers et al. (2004) suggested that in addition to the loss of nuclear stiffness, the loss of a physical interaction between nuclear structures (i.e., lamins) and the cytoskeleton may cause more general cellular weakness; they proposed a potential key function for lamins in maintaining cellular tensegrity. </p><p>Van Berlo et al. (2005) showed that A-type lamins were essential for the inhibition of fibroblast proliferation by TGF-beta-1 (190180). TGF-beta-1 dephosphorylated RB1 (614041) through protein phosphatase 2A (PPP2CA; 176915), both of which were associated with lamin A/C. In addition, lamin A/C modulated the effect of TGF-beta-1 on collagen production, a marker of mesenchymal differentiation. Van Berlo et al. (2005) proposed a role for lamin A/C in control of gene activity downstream of TGF-beta-1, via nuclear phosphatases such as PPP2CA. </p><p>Capanni et al. (2005) showed that the lamin A precursor was specifically accumulated in lipodystrophy cells. Pre-lamin A was located at the nuclear envelope and colocalized with SREBP1. Binding of SREBP1 to the lamin A precursor was detected in patient fibroblasts, as well as in control fibroblasts, forced to accumulate pre-lamin A by farnesylation inhibitors. In contrast, SREBP1 did not interact in vivo with mature lamin A or C in cultured fibroblasts. Inhibition of lamin A precursor processing in 3T3-L1 preadipocytes resulted in sequestration of SREBP1 at the nuclear rim, thus decreasing the pool of active SREBP1 that normally activates PPAR-gamma (601487) and causing impairment of preadipocyte differentiation. This defect could be rescued by treatment with troglitazone, a known PPAR-gamma ligand activating the adipogenic program. </p><p>Using yeast 2-hybrid analysis and protein pull-down assays, Libotte et al. (2005) found that the last 4 spectrin repeats at the C terminus of nesprin-2 (SYNE2; 608442), a nuclear membrane scaffold protein, bound directly to a C-terminal region common to both lamins A and C. Knockdown studies with human cell lines revealed that lamin A/C was required for nesprin-2 nuclear envelope localization. </p><p>Scaffidi and Misteli (2006) showed that the same molecular mechanism responsible for Hutchinson-Gilford progeria syndrome (HGPS; 176670) is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. Scaffidi and Misteli (2006) concluded that their observations implicate lamin A in physiologic aging. </p><p>Human immunodeficiency virus (HIV)-1 (see 609423) protease inhibitors (PIs) targeting the viral aspartyl protease are a cornerstone of treatment for HIV infection and disease, but they are associated with lipodystrophy and other side effects. Coffinier et al. (2007) found that treatment of human and mouse fibroblasts with HIV-PIs caused an accumulation of prelamin A. The prelamin A in HIV-PI-treated fibroblasts migrated more rapidly than nonfarnesylated prelamin A, comigrating with the farnesylated form found in ZMPSTE24 (606480)-deficient fibroblasts. HIV-PI-treated heterozygous ZMPSTE24 fibroblasts exhibited an exaggerated accumulation of farnesyl-prelamin A. Western blot and enzymatic analysis showed that HIV-PIs inhibited ZMPSTE24 activity and endoproteolytic processing of a GFP-prelamin A fusion protein, but they did not affect farnesylation of HDJ2 (DNAJA1; 602837) or activity of farnesyltransferase (see 134635), ICMT (605851), and RCE1 (605385) in vitro. Coffinier et al. (2007) concluded that HIV-PIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A, possibly explaining HIV-PI side effects. </p><p>Prelamin A is normally prenylated at cys661 (C661), then proteolytically processed by ZMPSTE24 into mature lamin A with a C-terminal Y646 residue. By transfecting HEK293 cells with cDNAs encoding prelamin A with various point mutations, Pan et al. (2007) determined that prenylation at C661 was not necessary for proteolytic processing and targeting of mature lamin A to the nuclear lamina. However, prelamin A that was prenylated but could not be C-terminally processed by ZMPSTE24 mislocalized to the nuclear pore complex. Inhibition of prenylation resulted in correct targeting of mutant prelamin A, suggesting that prenylation itself contributed to mislocalization. Since inhibition of prenylation in cultured cells also inhibits accumulation of progerin at the nuclear pore complex, Pan et al. (2007) proposed that accumulation of prenylated protein at the nuclear pore complex causes nuclear dysmorphology and is cytotoxic. </p><p>The nuclear envelope LINC (links the nucleoskeleton and cytoskeleton) complex, which is formed by SUN (e.g., SUN1, 607723) and nesprin (e.g., SYNE1, 608441) proteins, provides a direct connection between the nuclear lamina and the cytoskeleton. Haque et al. (2010) stated that SUN1 and SUN2 interact with LMNA and that LMNA is required for the nuclear envelope localization of SUN2, but not SUN1. They found that LMNA mutations associated with Emery-Dreifuss muscular dystrophy (EDMD2; 181350) and HGPS disrupted interaction of LMNA with mouse Sun1 and human SUN2. Nuclear localization of SUN1 and SUN2 was not impaired in EDMD2 or HGPS cell lines. Expression of SUN1, but not SUN2, at the nuclear envelope was enhanced in some HGPS cells, likely due to increased interaction of SUN1 with accumulated prelamin A. Haque et al. (2010) proposed that different perturbations in LMNA-SUN protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics. </p><p>Nuclei are precisely positioned in skeletal muscle, with a small number clustered under neuromuscular junctions, and the remainder equally spaced along the periphery of the fiber. By screening 16 different disease-causing lamin A variants, Folker et al. (2011) found that nearly all variants affected microtubule-dependent centrosome orientation, but only those that caused striated muscle disease disturbed actin-dependent nuclear movement and positioning. Wildtype, but not mutant, lamin A anchored SUN- and nesprin-containing LINC complexes that attach nuclei to retrogradely moving actin filaments. </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>Chen et al. (2012) showed that cells from Lmna -/- mice, which represent EDMD2, cells from Lmna(L530P/L530P) mice, which represent HGPS, and cells from HGPS patients all had overaccumulation of the inner nuclear envelope SUN1 protein. In wildtype cells, Lmna and Sun1 colocalized at the nuclear envelope. In Lmna -/- cells, larger amounts of Sun1 were found at the nuclear envelope and also in the Golgi. The larger amounts of Sun1 appeared to result from reduced protein turnover. Transfection of increasing amounts of mouse Sun1 into Lmna-null/Sun1-null murine cells resulted in increased prevalence of nuclear herniations and apoptosis, and the herniations appeared to result from Sun1 accumulation in the Golgi. Loss of the Sun1 gene in both mouse models extensively rescued cellular, tissue, organ, and lifespan abnormalities. Similarly, knockdown of overaccumulated SUN1 protein in primary human HGPS cells corrected nuclear defects and cellular senescence. The findings indicated that accumulation of SUN1 is a common pathogenetic event in these disorders. </p><p>Jung et al. (2012) found that mouse prelamins A and C both contain at least 1 binding site for microRNA-9 (MIR9; 611186) in their 3-prime UTRs. Mir9 downregulated lamin A expression by reducing prelamin A mRNA, but it did not downregulate lamin C expression. The findings suggested that high expression of Mir9 causes the low amount of lamin A, relative to lamin C, in mouse brain. </p><p>Using knockin mice expressing prelamin A with alterations in its 3-prime UTR, Jung et al. (2014) showed that Mir9 repressed lamin A expression in cerebral cortex and cerebellum. Mutation of the Mir9-binding site in the 3-prime UTR of prelamin A or replacement of the 3-prime UTR of prelamin A with that of prelamin C resulted in enhanced lamin A expression in brain. Jung et al. (2014) proposed that reduced expression of prelamin A in brain might explain why children with HGPS are spared neurodegenerative disease. </p><p>In mice, Ho et al. (2013) found that lamin A/C-deficient (Lmna-null) and Lmna(N195K/N195K) (see 150330.0007) mutant cells have impaired nuclear translocation and downstream signaling of the mechanosensitive transcription factor megakaryoblastic leukemia-1 (MKL1; 606078), a myocardin family member that is pivotal in cardiac development and function. Altered nucleocytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna-null and Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin (300384), which is mislocalized in Lmna mutant cells and also linked to Emery-Dreifuss muscular dystrophy (310300) and dilated cardiomyopathy, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. Ho et al. (2013) concluded that their findings presented a novel mechanism that could provide insight into the disease etiology for the cardiac phenotype in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization. </p><p>Simon et al. (2013) hypothesized that extensive posttranslational modification of mature lamin A may regulate its interactions with its binding partners, including actin, titin (TTN; 188840), emerin, and SREBP1. They found that lys420 (K420) and K486 in lamin A were modified by SUMO1. K420 lies within the nuclear localization signal, and K486 lies within the immunoglobulin (Ig)-fold. Simon et al. (2013) proposed that SUMO modification of K420 might inhibit lamin A/C binding to cyclin D3 (CCND3; 123834) or core histones that require an unmodified nuclear localization signal, or that it might inhibit binding of lamin A/C to alpha-importin (see 600686). They suggested that SUMO1 modification of K486 might block partners that require an unmodified Ig-fold. </p><p>Using in situ proximity ligation assays, reporter gene assays, and biochemical analysis, Vadrot et al. (2015) found that the interaction of SREBP1 with lamin A and lamin C occurs at the nuclear periphery and in the nucleoplasm. Interactions involved the Ig fold common to preLMNA, LMNA, and LMNC, and were stronger when SREBP1 was bound to sterol response elements (SREs) in DNA. SREBP1, LMNA, and SREs formed ternary complexes in vitro. The interaction was inhibitory, and overexpression of A-type lamins reduced transcriptional activity of SREBP1. </p><p><strong><em>Reviews</em></strong></p><p>
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Schreiber and Kennedy (2013) reviewed the disorders caused by mutations in nuclear lamins and other proteins of the nuclear envelope as well as the mechanisms underlying disease pathology. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Mutations in the LMNA gene cause a wide range of human diseases. Since more than 10 different clinical syndromes have been attributed to LMNA mutations, many of which show overlapping features, attempts at broad classification have been proposed. Worman and Bonne (2007) suggested that the disorders may be classified into 4 major types: diseases of striated and cardiac muscle; lipodystrophy syndromes; peripheral neuropathy; and premature aging. Benedetti et al. (2007) suggested 2 main groups: (1) neuromuscular and cardiac disorders, and (2) lipodystrophy and premature aging disorders. The phenotypic heterogeneity of diseases resulting from a mutation in a single gene can be explained by the numerous roles of the nuclear lamina, including maintenance of nuclear shape and structure, as well as functional roles in transcriptional regulation and heterochromatin organization (review by Capell and Collins, 2006). </p><p>Genschel and Schmidt (2000) compiled a list of 41 known mutations, predominantly missense, in the LMNA gene. Twenty-three different mutations had been shown to cause autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350). Three mutations had been reported to cause what was formerly designated autosomal dominant limb-girdle muscular dystrophy (LGMD1B), reclassified as EDMD2 by Straub et al. (2018). Eight mutations were known to result in dilated cardiomyopathy (CMD1A; 115200), and 7 mutations were reported to cause familial partial lipodystrophy (FPLD2; 151660). In addition, 1 mutation in LMNA (H222Y; 150330.0014) appeared to be responsible for an autosomal recessive, atypical form of Emery-Dreifuss muscular dystrophy (EDMD3; 616516). </p><p><strong><em>Muscular Dystrophies</em></strong></p><p>
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In 5 families with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), Bonne et al. (1999) identified 4 mutations in the LMNA gene (150330.0001-150330.0004) that cosegregated with the disease phenotype. These findings represented the first identification of mutations in a component of the nuclear lamina as a cause of an inherited muscle disorder. The authors noted that lamins interact with integral proteins of the inner nuclear membrane, including emerin (300384), which is mutated in the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD1; 310300). </p><p>Raffaele di Barletta et al. (2000) showed that heterozygous mutations in LMNA may cause diverse phenotypes ranging from typical EDMD to no phenotypic effect. LMNA mutations in patients with autosomal dominant EDMD occur in the tail and in the 2A rod domain of the protein, suggesting that unique interactions between lamin A/C and other nuclear components have an important role in cardiac and skeletal muscle function. They identified a homozygous LMNA mutation (H222Y; 150330.0014) in 1 patient born of consanguineous unaffected parents, consistent with autosomal recessive inheritance (EDMD3) and a severe atypical phenotype lacking cardiac features. </p><p>Muchir et al. (2000) found mutations in the LMNA gene in 3 families with LGMD1B, reclassified as EDMD2 by Straub et al. (2018): a missense mutation (150330.0017), a deletion of a codon (150330.0018), and a splice donor site mutation (150330.0019). The 3 mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. </p><p>Quijano-Roy et al. (2008) described a form of congenital muscular dystrophy (MDC) with onset in the first year of life in 15 children resulting from de novo heterozygous mutations in the LMNA gene (see, e.g., 150330.0047-150330.0049). Three patients had severe early-onset disease, with decreased fetal movements in utero, no motor development, severe hypotonia, diffuse limb and axial muscle weakness and atrophy, and talipes foot deformities. The remaining 12 children initially acquired head and trunk control and independent ambulation, but most lost head control due to neck extensor weakness, a phenotype consistent with 'dropped head syndrome.' Ten children required ventilatory support. Cardiac arrhythmias were observed in 4 of the oldest patients, but were symptomatic only in 1. Quijano-Roy et al. (2008) concluded that the identified LMNA mutations appeared to correlate with a relatively severe phenotype, broadening the spectrum of laminopathies. The authors suggested that this group of patients may define a new disease entity, which they designated LMNA-related congenital muscular dystrophy (613205). </p><p>Benedetti et al. (2007) reported 27 individuals with mutations in the LMNA gene resulting in a wide range of neuromuscular disorders. Phenotypic analysis yielded 2 broad groups of patients. One group included patients with childhood onset who had skeletal muscle involvement with predominant scapuloperoneal and facial weakness, consistent with EDMD or congenital muscular dystrophy. The second group included patients with later or adult onset who had cardiac disorders or a limb-girdle myopathy, consistent with LGMD1B. Those in the group with early onset tended to have missense mutations, whereas those in the group with adult onset tended to have truncating mutations. Analysis of the variants showed that those associated with early-onset phenotypes were primarily found in the Ig-like domain and in coil 2A, which may interfere with binding to specific ligands. Those associated with later onset were mostly located in the rod domain and in coil 2B, which was predicted to affect the surface of lamin A/C dimers and lead to impaired filament assembly. Benedetti et al. (2007) speculated that there may be 2 different pathogenetic mechanisms associated with neuromuscular LMNA-related disorders: late-onset phenotypes may arise through loss of LMNA function secondary to haploinsufficiency, whereas dominant-negative or toxic gain-of-function mechanisms may underlie the more severe early phenotypes. </p><p>Scharner et al. (2011) identified LMNA mutations in 61 (23.9%) of 255 patients with muscular dystrophy. Eleven of the patients had previously been reported by Brown et al. (2001). Among the remaining 50 patients from the United States and Canada, Scharner et al. (2011) found 37 mutations, including 15 novel ones. The mutations were scattered throughout the gene. In vitro functional expression studies performed on some of the mutations (e.g., R249W; 150330.0048) showed that they resulted in increased expression of mutant LMNA, mislocalization of the protein in the nucleus, abnormal nuclear morphology with lobules, and mislocalization of lamin B (LMNB; 150340). </p><p>In 4 sibs, born of consanguineous Spanish parents, with EDMD3, Jimenez-Escrig et al. (2012) identified a homozygous missense mutation in the LMNA gene (R225Q; 150330.0054). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in 200 control chromosomes. Functional studies of the variant were not performed. Two heterozygous carriers had no muscular symptoms, but developed cardiac arrhythmias late in life. </p><p>In 2 sibs from a family of Hutterite descent with EDMD3 and features of partial lipodystrophy, Wiltshire et al. (2013) identified a homozygous missense mutation in the LMNA gene (R482Q; 150330.0010). </p><p><strong><em>Dilated Cardiomyopathy and Cardiac Conduction Defects</em></strong></p><p>
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Fatkin et al. (1999) studied the LMNA gene in 11 families with autosomal dominant dilated cardiomyopathy and conduction system disease (CMD1A; 115200) linked to a region on chromosome 1 overlapping that of the LMNA gene. They identified 5 novel missense mutations (150330.0004-150330.0009): 4 in the alpha-helical rod domain of lamin A, and 1 in the tail domain of lamin C. No family members with mutations had joint contractures or skeletal myopathy characteristic of autosomal dominant Emery-Dreifuss muscular dystrophy. Furthermore, serum creatine kinase levels were normal in family members with mutations of the lamin A rod domain, but mildly elevated in some family members with a defect in the lamin C tail domain. The authors noted that mutations in the rod domain of the protein led to dilated cardiomyopathy, whereas mutations in the head or tail domain caused Emery-Dreifuss muscular dystrophy. </p><p>Van der Kooi et al. (2002) reported a sporadic patient and 2 unrelated families with mutations in the LMNA gene who presented with varying degrees and combinations of muscular dystrophy, partial lipodystrophy, and cardiomyopathy with conduction defects, presumably due to single mutations (see 150330.0003 and 150330.0005). </p><p>Sebillon et al. (2003) screened the coding sequence of LMNA in DNA samples from 66 index cases of dilated cardiomyopathy with or without associated features. They identified a glu161-to-lys mutation (E161K; 150330.0028) in a family with early-onset atrial fibrillation preceding or coexisting with dilated cardiomyopathy, the previously described R377H mutation (150330.0017) in the family with quadriceps myopathy associated with dilated cardiomyopathy previously reported by Charniot et al. (2003), and a 28insA mutation (150330.0029) leading to a premature stop codon in a third family with dilated cardiomyopathy with conduction defects. No mutation in LMNA was found in cases with isolated dilated cardiomyopathy. </p><p>Meune et al. (2006) investigated the efficacy of implantable cardioverter-defibrillators (ICDs) in the primary prevention of sudden death in patients with cardiomyopathy due to lamin A/C gene mutations. Patients referred for permanent cardiac pacing were systematically offered the implantation of an ICD. The patients were enrolled solely on the basis of the presence of lamin A/C mutations associated with cardiac conduction defects. Indications for pacemaker implantation were progressive conduction block and sinus block. In all, 19 patients were treated. Meune et al. (2006) concluded that ICD implantation in patients with lamin A/C mutations who are in need of a pacemaker is effective in treating possibly lethal tachyarrhythmias, and that implantation of an ICD, rather than a pacemaker, should be considered for such patients. </p><p>Taylor et al. (2003) screened the LMNA gene in 40 families and 9 sporadic patients with CMD with or without muscular dystrophy and identified mutations in 3 families (see, e.g., 150330.0017) and 1 sporadic patient (S573L; 150330.0041). All mutations involved a conserved residue, cosegregated with the disease within the families, and were not found in 300 control chromosomes. LMNA mutation carriers had a severe and progressive form of CMD with significantly poorer cumulative survival compared to noncarrier CMD patients. </p><p><strong><em>Dilated Cardiomyopathy and Hypergonadotropic Hypogonadism</em></strong></p><p>
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In a 17-year-old Caucasian female with premature ovarian failure and dilated cardiomyopathy, who had features consistent with atypical Werner syndrome (see 277700) but who was negative for mutation in the RECQL2 gene (604611), Nguyen et al. (2007) identified heterozygosity for a missense mutation in the LMNA gene (L59R; 150330.0052). The authors suggested the diagnosis of a laminopathy, most likely an atypical form of mandibuloacral dysplasia (see 248370). </p><p>In a 15-year-old Caucasian girl with premature ovarian failure and dilated cardiomyopathy, McPherson et al. (2009) identified heterozygosity for the L59R mutation in the LMNA gene. McPherson et al. (2009) noted phenotypic similarities between this patient and the patient previously reported by Nguyen et al. (2007), who carried the same mutation, as well as a patient originally described by Chen et al. (2003) with an adjacent A57P mutation in LMNA (150330.0030). 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 involving dilated cardiomyopathy and hypergonadotropic hypogonadism (212112). </p><p><strong><em>Lipodystrophy Disorders</em></strong></p><p>
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Patients with Dunnigan-type familial partial lipodystrophy, or partial lipodystrophy type 2 (FPLD2; 151660), are born with normal fat distribution, but after puberty experience regional and progressive adipocyte degeneration, often associated with profound insulin resistance and diabetes. Cao and Hegele (2000) hypothesized that the analogy between the regional muscle wasting in autosomal dominant Emery-Dreifuss muscular dystrophy and the regional adipocyte degeneration in FPLD, in addition to the chromosomal localization of the FPLD2 locus on 1q21-q22, made LMNA a good candidate gene for FPLD2. Studies of 5 Canadian probands with familial partial lipodystrophy of Dunnigan type indicated that each had a novel missense mutation (R482Q; 150330.0010) that cosegregated with the lipodystrophy phenotype and was absent from 2,000 normal alleles. </p><p>Shackleton et al. (2000) identified 5 different missense mutations in the LMNA gene (see, e.g., 150330.0010-150330.0012) among 10 kindreds and 3 individuals with partial lipodystrophy. All of the mutations occurred in exon 8, which the authors noted is within the C-terminal globular domain of lamin A/C. Flier (2000) commented on the significance of LMNA mutations in partial lipodystrophy. </p><p>Vantyghem et al. (2004) characterized the neuromuscular and cardiac phenotypes of FPLD patients bearing the heterozygous R482W mutation. Fourteen patients from 2 unrelated families, including 10 affected subjects, were studied. Clinical and histologic examination showed an incapacitating, progressive limb-girdle muscular dystrophy in a 42-year-old woman that had been present since childhood, associated with a typical postpubertal FPLD phenotype. Six of 8 adults presented the association of calf hypertrophy, perihumeral muscular atrophy, and a rolling gait due to proximal lower limb weakness. Muscular histology was compatible with muscular dystrophy in one of them and/or showed a nonspecific excess of lipid droplets (in 3 cases). Cardiac septal hypertrophy and atherosclerosis were frequent in FPLD patients. In addition, a 24-year-old FPLD patient had a symptomatic second-degree atrioventricular block. Vantyghem et al. (2004) concluded that most lipodystrophic patients affected by the FPLD-linked R482W mutation show muscular and cardiac abnormalities. </p><p>Mandibuloacral dysplasia (see 248370) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. Patients with MAD frequently have partial lipodystrophy and insulin resistance, which are features seen in FPLD. In all affected members of 5 consanguineous Italian families with MAD, Novelli et al. (2002) identified a homozygous missense mutation (R527H; 150330.0021) in the LMNA gene. Patient skin fibroblasts showed nuclei that presented abnormal lamin A/C distribution and a dysmorphic envelope, demonstrating the pathogenic effect of the mutation. </p><p>In affected members of a consanguineous family from north India, Plasilova et al. (2004) identified a homozygous missense mutation in the LMNA gene (150330.0033). The extent of skeletal lesions in this family were consistent with MAD, but affected individuals also had classic features of progeria. Plasilova et al. (2004) suggested that autosomal recessive HGPS and mandibuloacral dysplasia may represent a single disorder with varying degrees of disease severity. </p><p>Decaudain et al. (2007) identified changes in codon 482 of the LMNA gene (see, e.g., R482Q, 150330.0010 and R482W, 150330.0011) in 17 of 277 unrelated adults investigated for lipodystrophy and/or insulin resistance. All 17 had classic features of FPLD2. Ten additional patients who fulfilled the International Diabetes Federation diagnostic criteria for metabolic syndrome were found to have heterozygous LMNA mutations that were not in codon 482, but affected all 3 domains of the protein, the N terminal, central rod domain, and C terminal globulin domain (see, e.g., R399C; 150330.0043). Because the phenotype of these patients was not typical of FPLD2, the diagnosis of laminopathy was delayed. Although lipodystrophy was less severe than in typical FPLD2, common features included calf hypertrophy, myalgia, and muscle cramps or weakness. Two patients had cardiac conduction disturbances. Metabolic alterations were prominent, especially insulin resistance and hypertriglyceridemia. </p><p><strong><em>Charcot-Marie-Tooth Disease Type 2B1</em></strong></p><p>
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In affected members of inbred Algerian families with an axonal form of Charcot-Marie-Tooth disease linked to chromosome 1q21.2-q21.3 (CMT2B1; 605588), De Sandre-Giovannoli et al. (2002) found a shared common homozygous ancestral haplotype that was suggestive of a founder mutation and identified a unique mutation in the LMNA rod domain (R298C; 150330.0020). Ultrastructural studies of sciatic nerves of Lmna-null mice showed a strong reduction of axon density, axonal enlargement, and the presence of nonmyelinated axons, all of which were highly similar to the phenotypes of human peripheral axonopathies. </p><p><strong><em>Hutchinson-Gilford Progeria Syndrome and Other Premature Aging Syndromes</em></strong></p><p>
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Eriksson et al. (2003) identified de novo heterozygous point mutations in lamin A that cause Hutchinson-Gilford progeria syndrome (HGPS; 176670). Eighteen of 20 classic cases of HGPS harbored the identical de novo single-base substitution resulting in a silent gly-to-gly change at codon 608 within exon 11 (150330.0022). This change creates an exonic consensus splice site and activates cryptic splicing, leading to deletion of 50 codons at the end of prelamin A. This prelamin A still retains the CAAX box but lacks the site for endoproteolytic cleavage. Eriksson et al. (2003) suggested that there is at least 1 site for phosphorylation, ser625, that is deleted in the abnormal lamin A protein. De Sandre-Giovannoli et al. (2003) independently identified the heterozygous exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del; 150330.0022) in 2 HGPS patients. Later cellular studies (Capell et al., 2005; Glynn and Glover, 2005; Toth et al., 2005) indicated that Hutchinson-Gilford progeria syndrome results from the production of a truncated prelamin A, called progerin, which is farnesylated at its C terminus and accumulates at the nuclear envelope, causing misshapen nuclei (Yang et al., 2006). </p><p>Werner syndrome (277700) is an autosomal recessive progeroid syndrome caused by mutation in the RECQL2 gene (WRN; 604611). Chen et al. (2003) reported that of 129 index patients referred to their international registry for molecular diagnosis of Werner syndrome, 26 (20%) had wildtype RECQL2 coding regions and were categorized as having 'atypical Werner syndrome' or 'non-WRN' on the basis of molecular criteria. Because of some phenotypic similarities between Werner syndrome and laminopathies including Hutchinson-Gilford progeria, Chen et al. (2003) sequenced all exons of the LMNA gene in these 26 individuals and found heterozygosity for novel missense mutations in LMNA in 4 (15%): A57P (150330.0030), R133L (150330.0027) in 2 persons, and L140R (150330.0031). Hegele (2003) stated that the clinical designation of Werner syndrome for each of the 4 patients of Chen et al. (2003), in whom mutations in the LMNA gene were found, 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 Hutchinson-Gilford syndrome as with early-onset Werner syndrome. Patients with so-called atypical Werner syndrome and mutant LMNA also expressed components of nonprogeroid laminopathies. 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) suggested that the patient in whom Chen et al. (2003) identified an A57P LMNA mutation had a distinct phenotype involving dilated cardiomyopathy and hypergonadotropic hypogonadism (212112). </p><p>Csoka et al. (2004) screened 13 cell lines from atypical progeroid patients for mutation in the LMNA gene. They identified 3 novel heterozygous missense mutations in the LMNA gene in 3 patients: a 13-year-old female with a progeroid syndrome, a 15-year-old male with a lipodystrophy, and a 20-year-old male with 'atypical progeria.' The mutations identified in the last 2 patients were the most 5-prime and 3-prime missense mutations, respectively, that had been identified in LMNA. </p><p>Reddel and Weiss (2004) reported that transcription efficiencies of the mutant and wildtype LMNA alleles were equivalent in HGPS. The mutant allele gave 2 types of transcripts that encoded truncated and normal lamin A. Abnormally spliced progerin transcript constituted the majority (84.5%) of the total steady-state mRNA derived from the mutant allele. The abnormally spliced progerin transcript was a minority (40%) of all lamin A transcripts obtained from both alleles. Reddel and Weiss (2004) concluded that the mutated progerin functions as a dominant negative by interfering with the structure of the nuclear lamina, intranuclear architecture, and macromolecular interactions, which collectively would have a major impact on nuclear function. </p><p>Fibroblasts from individuals with HGPS have severe morphologic abnormalities in nuclear envelope structure. Scaffidi and Misteli (2005) showed that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wildtype lamin A protein did not rescue the cellular disease manifestations. The mutant LMNA mRNA and lamin A protein could be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assumed normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins were rescued, defects in heterochromatin-specific histone modifications were corrected, and proper expression of several misregulated genes was reestablished. The results established proof of principle for the correction of the premature aging phenotype in individuals with HGPS. </p><p>Huang et al. (2005) designed short hairpin RNAs (shRNA) targeting mutated pre-spliced or mature LMNA mRNAs and expressed them in HGPS fibroblasts carrying the 1824C-T mutation (150330.0022). One of the shRNAs reduced the expression levels of mutant lamin A (so-called LA delta-50) to 26% or lower. The reduced expression was associated with amelioration of abnormal nuclear morphology, improvement of proliferative potential, and reduction in the numbers of senescent cells. </p><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 that is also 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 with severity of disease. </p><p>Scaffidi and Misteli (2008) found that progerin (150330.0022) expression in immortalized human skin fibroblasts produced several defects typical of HGPS. Progerin also caused the spontaneous differentiation of human mesenchymal stem cells (MSCs) into endothelial cells, and reduced their differentiation along the adipogenic lineage. Abnormal differentiation of MSCs appeared to be due to progerin-induced activation of major downstream effectors of the Notch signaling pathway, including HES1 (139605), HES5 (607348), and HEY1 (602953). Scaffidi and Misteli (2008) noted that the progerin splice variant of LMNA is present at low levels in cells from healthy individuals and has been implicated in the normal aging process. They suggested that progerin-induced defects in Notch signaling are involved in normal aging and similarly affect adult MSCs and their differentiation. </p><p>In affected members of a nonconsanguineous family with an atypical form of HGPS manifest as adult-onset coronary disease and progeroid features, Hisama et al. (2011) identified a heterozygous splice site mutation affecting exon 11 of 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. </p><p>In affected members of a family with a protracted form of HGPS (see 176670) manifest as premature cutaneous and cardiac aging in young adulthood, 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><strong><em>Restrictive Dermopathy 2</em></strong></p><p>
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In 2 of 9 patients with restrictive dermopathy (RSMD2; 619793), a lethal genodermatosis in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence, Navarro et al. (2004) identified heterozygous splicing mutations in the LMNA gene, resulting in the complete or partial loss of exon 11 (150330.0036 and 150330.0022, respectively). In the other 7 patients, they identified a heterozygous 1-bp duplication resulting in a premature stop codon in the zinc metalloproteinase STE24 gene (ZMPSTE24; 606480). This gene encodes a metalloproteinase specifically involved in the posttranslational processing of lamin A precursor. In all patients carrying a ZMPSTE24 mutation, loss of expression of lamin A as well as abnormal patterns of nuclear sizes and shapes and mislocalization of lamin-associated proteins was seen. Navarro et al. (2004) concluded that a common pathogenetic pathway, involving defects of the nuclear lamina and matrix, is involved in restrictive dermopathy. </p><p>Navarro et al. (2005) described 7 previously reported patients and 3 new patients with restrictive dermopathy who were homozygous or compound heterozygous for ZMPSTE24 mutations. In all cases there was complete absence of both ZMPSTE24 and mature lamin A, associated with prelamin A accumulation. The authors concluded that restrictive dermopathy is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations. The accumulation of truncated or normal length prelamin A is, therefore, a shared pathophysiologic feature in recessive and dominant restrictive dermopathy. </p><p><strong><em>Heart-Hand Syndrome, Slovenian Type</em></strong></p><p>
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In a Slovenian family with heart-hand syndrome (610140), originally reported by Sinkovec et al. (2005), Renou et al. (2008) identified a splice site mutation in the LMNA gene (150330.0045) that segregated with disease and was not found in 100 healthy controls. Analysis of fibroblasts from 2 affected members of the family revealed truncated lamin A/C protein and nuclear envelope abnormalities, confirming the pathogenicity of the mutation. </p><p>In affected members of a family with Slovenian-type heart-hand syndrome, Zaragoza et al. (2017) identified heterozygosity for a missense mutation in the LMNA gene (R335W; 150330.0058) that segregated with the disorder in the family. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </p><p><strong><em>Other Associations</em></strong></p><p>
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Hegele et al. (2000) identified a common single-nucleotide polymorphism (SNP) in LMNA, 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. Hegele et al. (2001) reported association of this LMNA SNP with anthropometric indices in 186 nondiabetic Canadian Inuit. They found that physical indices of obesity, such as body mass index, waist circumference, waist-to-hip circumference ratio, subscapular skinfold thickness, and subscapular-to-triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for approximately 10 to 100% of the attributable variation. The results indicated that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>In 14 of 15 families with familial partial lipodystrophy, Speckman et al. (2000) identified mutations in exon 8 of the LMNA gene: 5 families had an R482Q mutation (150330.0010); 7 families had an R482W alteration (150330.0011), and 1 family had a G465D alteration (150330.0015). The R482Q and R482W mutations occurred on different haplotypes, indicating that they probably had arisen more than once. One family with an atypical form of familial partial lipodystrophy had an R582H mutation (150330.0016) in exon 11 of the LMNA gene, which the authors noted can affect the lamin A protein only. Speckman et al. (2000) noted that all mutations in Dunnigan lipodystrophy affect the globular C-terminal domain of the lamin A/C protein, whereas mutations responsible for dilated cardiomyopathy and conduction-system disease are usually clustered in the rod domain of the protein (Fatkin et al., 1999). Speckman et al. (2000) could not detect mutations in the LMNA gene in 1 FPLD family that showed linkage to 1q21-q23. </p><p>Hegele (2005) used hierarchical cluster analysis to assemble 16 laminopathy phenotypes into 2 classes based on organ system involvement, and then classified 91 reported causative LMNA mutations according to their position upstream or downstream of the nuclear localization signal (NLS) sequence. Contingency analysis revealed that laminopathy class and LMNA mutation position were strongly correlated (p less than 0.0001), suggesting that laminopathy phenotype and LMNA genotype are nonrandomly associated. </p><p>Lanktree et al. (2007) analyzed the LMNA gene in 3 unrelated patients with FPLD2 and identified heterozygosity for 3 different missense mutations, all affecting only the lamin A isoform and each changing a conserved residue. Two of the mutations, D230N (150330.0042) and R399C (150330.0043), were 5-prime to the NLS, which is not typical of LMNA mutations in FPLD2. The third mutation, S573L (150330.0041), had previously been identified in heterozygosity in a patient with dilated cardiomyopathy and conduction defects (CMD1A; 115200) and in homozygosity in a patient with arthropathy, tendinous calcinosis, and progeroid features (see 248370). None of the mutations were found in 200 controls of multiple ethnicities. Because heterozygosity for an S573L mutation can cause cardiomyopathy without lipodystrophy or lipodystrophy without cardiomyopathy, Lanktree et al. (2007) suggested that additional factors, genetic or environmental, may contribute to the precise tissue involvement. </p><p>Gupta et al. (2010) analyzed the LMNA gene in heart samples from 25 unrelated CMD patients and identified 3 heterozygous missense mutations in 3 patients as well as a heterozygous deletion of exons 3 to 12 in 1 patient. The LMNA deletion and 1 of the missense mutations were associated with major cardiomyocyte nuclear envelope abnormalities, whereas the other 2 missense mutations were found in patients without specific nuclear envelope abnormalities. Gupta et al. (2010) stated that they did not find any evidence of a genotype/phenotype relationship between the onset and severity of CMD, the presence of nuclear abnormalities, and the presence or absence of LMNA mutations. </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 (150330.0036, 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 corresponding 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 (619793) 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>
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<strong>Animal Model</strong>
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<p>Mounkes et al. (2003) attempted to create a mouse model for autosomal dominant Emery-Dreifuss muscular dystrophy (181350) by introducing a L530P (150330.0004) mutation in the LMNA gene. Although mice heterozygous for L530P did not show signs of muscular dystrophy and remained overtly normal up to 6 months of age, mice homozygous for the mutation showed phenotypes markedly reminiscent of symptoms observed in progeria patients. Homozygous Lmna L530P/L530P mice were indistinguishable from their littermates at birth, but by 4 to 6 days developed severe growth retardation, dying within 4 to 5 weeks. Homozygous mutant mice showed a slight waddling gait, suggesting immobility of joints. Other progeria features of these mutant mice included micrognathia and abnormal dentition--in approximately half of the mutants a gap was observed between the lower 2 incisors, which also appeared yellowed. Mutant mice also had loss of subcutaneous fat, reduced numbers of eccrine and sebaceous glands, increased collagen deposition in skin, and decreased hair follicle density. Mounkes et al. (2003) concluded that Lmna L530P/L530P mice have significant phenotypic overlap with Hutchinson-Gilford progeria syndrome, including nuclear envelope abnormalities and decreased doublet capacity and life span of fibroblasts. </p><p>Mounkes et al. (2005) generated mice expressing the human N195K (150330.0007) mutation and observed characteristics consistent with CMD1A. Continuous electrocardiographic monitoring of cardiac activity demonstrated that N195K-homozygous mice died at an early age due to arrhythmia. Immunofluorescence and Western blot analysis showed that Hf1b/Sp4 (600540), connexin-40 (GJA5; 121013), and connexin-43 (GJA1; 121014) were misexpressed and/or mislocalized in N195K-homozygous mouse hearts. Desmin staining revealed a loss of organization at sarcomeres and intercalated disks. Mounkes et al. (2005) hypothesized that mutations within the LMNA gene may cause cardiomyopathy by disrupting the internal organization of the cardiomyocyte and/or altering the expression of transcription factors essential to normal cardiac development, aging, or function. </p><p>Arimura et al. (2005) created a mouse model of autosomal dominant Emery-Dreifuss muscular dystrophy expressing an H222P mutation in Lmna. At adulthood, male homozygous mice displayed reduced locomotion activity with abnormal stiff walking posture, and all died by 9 months of age. They also developed dilated cardiomyopathy with hypokinesia and conduction defects. These skeletal and cardiac muscle features were also observed in the female homozygous mice, but with a later onset than in males. Histopathologic analysis of the mice revealed muscle degeneration with fibrosis associated with dislocation of heterochromatin and activation of Smad signaling in heart and skeletal muscles. </p><p>Varga et al. (2006) created transgenic mice carrying the G608G (150330.0022)-mutated human LMNA gene and observed the development of a dramatic defect of the large arteries, consisting of progressive medial vascular smooth muscle cell loss and replacement with proteoglycan and collagen followed by vascular remodeling with calcification and adventitial thickening. In vivo, these arterial abnormalities were reflected by a blunted initial response to the vasodilator sodium nitroprusside, consistent with impaired vascular relaxation, and attenuated blood pressure recovery after infusion. Varga et al. (2006) noted that although G608G transgenic mice lacked the external phenotype seen in human progeria, they demonstrated a progressive vascular abnormality that closely resembled the most lethal aspect of the human phenotype. </p><p>Frock et al. (2006) found that most cultured muscle cells from Lmna knockout mice exhibited impaired differentiation kinetics and reduced differentiation potential. Similarly, knockdown of Lmna or emerin (EMD; 300384) expression by RNA interference in normal muscle cells impaired differentiation potential and reduced expression of muscle-specific genes, Myod (159970) and desmin (125660). To determine whether impaired myogenesis was linked to reduced Myod or desmin levels, Frock et al. (2006) individually expressed these proteins in Lmna-null myoblasts and found that both increased the differentiation potential of mutant myoblasts. Frock et al. (2006) concluded that LMNA and emerin are required for myogenic differentiation, at least in part, through an effect on expression of critical myoblast proteins. </p><p>Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a truncated prelamin A, called progerin, which is farnesylated at its C terminus and accumulates at the nuclear envelope, causing misshapen nuclei (Yang et al., 2006). Farnesyltransferase inhibitors (FTIs) have been shown to reverse this cellular abnormality (Yang et al., 2005; Toth et al., 2005; Capell et al., 2005; Mallampalli et al., 2005). 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>Yang et al. (2008) created knockin mice expressing a nonfarnesylatable form of progerin. Knockin mice developed the same disease phenotype as mice expressing farnesylated progerin, although the phenotype was milder, and embryonic fibroblasts derived from these mice contained fewer misshapen nuclei. The steady-state level of nonfarnesylated progerin, but not mRNA, was lower in cultured fibroblasts and whole tissues, suggesting that the absence of farnesylation may accelerate progerin turnover. </p><p>In a mouse model of EDMD carrying an H222P mutation in the Lmna gene (Arimura et al., 2005), Muchir et al. (2007) found that activation of MAPK (see 176948) pathways preceded clinical signs or detectable molecular markers of cardiomyopathy. Expression of H222P-mutant Lmna in heart tissue and isolated cardiomyocytes resulted in tissue-specific activation of MAPKs and downstream target genes. The results suggested that activation of MAPK pathways plays a role in the pathogenesis of cardiac disease in EDMD. </p><p>Muchir et al. (2009) demonstrated abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P knockin mice, a model of autosomal Emery-Dreifuss muscular dystrophy. Systemic treatment of Lmna H222P/H222P mice that developed cardiomyopathy with PD98059, an inhibitor of ERK activation, inhibited ERK phosphorylation and blocked the activation of downstream genes in heart. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere organization that occurred in placebo-treated mice. Histologic analysis and echocardiography demonstrated that treatment with PD98059 delayed the development of left ventricular dilatation. PD98059-treated Lmna H222P/H222P mice had normal cardiac ejection fractions assessed by echocardiography, whereas placebo-treated mice had a 30% decrease. The authors emphasized the role of ERK activation in the development of cardiomyopathy caused by LMNA mutations, and provided further proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA. </p><p>Davies et al. (2010) created knockin mice harboring a mutant Lmna allele that yielded exclusively nonfarnesylated prelamin A. These mice had no evidence of progeria but succumbed to cardiomyopathy. Most of the nonfarnesylated prelamin A in the tissues of these mice was localized at the nuclear rim, indistinguishable from the lamin A in wildtype mice. The cardiomyopathy could not be ascribed to an absence of lamin C because mice expressing an otherwise identical knockin allele yielding only wildtype prelamin A appeared normal. The authors concluded that lamin C synthesis is dispensable in mice and that failure to convert prelamin A to mature lamin A causes cardiomyopathy in the absence of lamin C. </p><p>Choi et al. (2012) found that ERK activation in H222P/H222P mice specifically upregulated expression of dual-specificity phosphatase-4 (DUSP4; 602747) in cardiac muscle, with much lower Dusp4 induction in quadriceps muscle, and no Dusp4 induction in tongue, kidney, and liver. Dusp4 overexpression in cultured C2C12 muscle cells or targeted to mouse heart resulted in activation of the Akt (see AKT1; 164730)-Mtor (FRAP1; 601231) metabolic signaling pathway, leading to impaired autophagy and abnormal cardiac metabolism, similar to findings in H222P/H222P mice. </p><p>Thomasson et al. (2019) found that mice homozygous for the Lmna H222P mutation had depressed left ventricular function and altered body composition. The mutation decreased metabolic performance in mice and changed their physical activity. Supplementation with nicotinamide riboside (NR) in the diet partially restored the structure and function of striated muscles and improved the performance of mutant mice. </p><p>Wang et al. (2022) generated mice homozygous for a leu648-to-arg (L648R) mutation in Lmna, corresponding to the HGPS-causing L647R mutation in human LMNA that abolishes the prelamin A ZMPSTE24 cleavage site. Homozygous mutant mice expressed prelamin A and lamin C at roughly the same levels as wildtype, but they lacked mature lamin A. Mutant mice were viable, fertile, and grossly indistinguishable compared with wildtype, but they had unexpectedly long lifespans and low body mass and body fat. Microcomputed tomographic analysis revealed that homozygous mutant mice had cranial and mandibular defects with dental abnormalities, resembling those of Zmpste24 -/- mice and humans with HGPS mutations, but they appeared to be less severe and were not prominent until later in life. Mutant mice also exhibited decreased vertebral bone density and long bone defects, similar to Zmpste24 -/- mice, but they had normal grip strength with only rare rib fractures at old, preterminal ages. Analysis of embryonic fibroblasts from the mutant mice showed an accumulation of prelamin A and abnormal nuclear morphology, suggesting that accumulation of the farnesylated form of prelamin A was responsible for abnormal nuclear morphology. </p>
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<strong>ALLELIC VARIANTS</strong>
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<strong>58 Selected Examples):</strong>
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<strong>.0001 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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LMNA, GLN6TER
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SNP: rs61046466,
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gnomAD: rs61046466,
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ClinVar: RCV000015564, RCV000041328, RCV000057350
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), Bonne et al. (1999) identified a C-to-T transition in exon 1 of the LMNA gene that changed glutamine-6 (CAG) to a stop codon (TAG). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG453TRP
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<br />
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SNP: rs58932704,
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gnomAD: rs58932704,
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ClinVar: RCV000015565, RCV000057273, RCV000472112, RCV000500734, RCV001095717, RCV001813989, RCV003313922, RCV004639121
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), Bonne et al. (1999) demonstrated a C-to-T transition in exon 7 of the LMNA gene, resulting in an arg453-to-trp (R453W) substitution. </p>
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</span>
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|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
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|
</div>
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<div>
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<span class="mim-text-font">
|
|
LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
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|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
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LMNA, ARG527PRO
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<br />
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SNP: rs57520892,
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gnomAD: rs57520892,
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ClinVar: RCV000015569, RCV000015570, RCV000057327, RCV000700159, RCV001375641, RCV004018633
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
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|
<span class="mim-text-font">
|
|
<p>In 2 families with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), Bonne et al. (1999) found a G-to-C transversion in the LMNA gene which, resulting in an arg527-to-pro (R527P) substitution. The mutation, found in heterozygous state, was demonstrated to be de novo in both families. </p><p>Van der Kooi et al. (2002) reported a woman with limb-girdle muscle weakness, spinal rigidity, contractures, elevated creatine kinase, cardiac conduction abnormalities (atrial fibrillation), partial lipodystrophy (151660), and increased serum triglycerides who had the R527P mutation. Van der Kooi et al. (2002) also reported a family with the R527P mutation in which the proband, her father, and her son all presented with varying degrees of EDMD, lipodystrophy, and cardiac conduction abnormalities. </p><p>Makri et al. (2009) reported 2 sisters with early-onset autosomal dominant muscular dystrophy most consistent with EDMD. Because the girls were born of consanguineous Algerian parents, they were at first thought to have an autosomal recessive congenital muscular dystrophy. However, genetic analysis identified a heterozygous R527P mutation in the LMNA gene in both patients that was not present in either unaffected parent. The results were consistent with germline mosaicism or a recurrent de novo event. The older sib had a difficult birth and showed congenital hypotonia, diffuse weakness, and mild initial respiratory and feeding difficulties. She sat unsupported at age 2 years and walked independently from age 4 years with frequent falls and a waddling gait. At 13 years she had a high-arched palate, moderate limb hypotonia, and weakness of the pelvic muscles. There was proximal limb wasting, moderate cervical, elbow, and ankle contractures, pes cavus, spinal rigidity, and lordosis/scoliosis. Her sister had mild hypotonia in early infancy, walked without support at 24 months, and showed proximal muscle weakness. There were mild contractures of the elbow and ankles. At age 9 years, she showed adiposity of the neck, trunk and abdomen, consistent with lipodystrophy. Brain MRI and cognition were normal in both sisters, and neither had cardiac involvement. Muscle biopsies showed a dystrophic pattern. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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LMNA, LEU530PRO
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<br />
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SNP: rs60934003,
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|
|
ClinVar: RCV000015571, RCV000057333
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), Bonne et al. (1999) detected a heterozygous T-to-C transition in the LMNA gene, resulting in a leu530-to-pro (L530P) substitution. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
|
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</div>
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</div>
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|
<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
|
|
</span>
|
|
</div>
|
|
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG60GLY
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|
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|
|
|
<br />
|
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|
|
SNP: rs28928900,
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|
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|
|
|
gnomAD: rs28928900,
|
|
|
|
|
|
ClinVar: RCV000015566, RCV000015567, RCV000057359
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Dilated Cardiomyopathy 1A</em></strong></p><p>
|
|
In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; 115200), Fatkin et al. (1999) identified a 178C-G transversion in the LMNA gene, resulting in an arg60-to-gly (R60G) substitution. </p><p><strong><em>Familial Partial Lipodystrophy, Type 2</em></strong></p><p>
|
|
Van der Kooi et al. (2002) reported a woman with partial lipodystrophy (FPLD2; 151660), hypertriglyceridemia, and cardiomyopathy with conduction defects who carried the R60G mutation. The patient's mother reportedly had similar manifestations. The authors noted that lipodystrophy and cardiac abnormalities were combined manifestations of the same mutation. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
|
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</div>
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</div>
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|
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, LEU85ARG
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933090,
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|
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|
|
ClinVar: RCV000015568, RCV000057381, RCV002453264
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; 115200), Fatkin et al. (1999) identified a 254T-G transversion in the LMNA gene, resulting in a leu85-to-arg (L85R) substitution. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ASN195LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933091,
|
|
|
|
|
|
|
|
ClinVar: RCV000015572, RCV000057425, RCV000211789, RCV000794743
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; 115200), Fatkin et al. (1999) identified a 585C-G transversion in the LMNA gene, resulting in an asn195-to-lys (N195K) substitution. </p><p><strong><em>Variant Function</em></strong></p><p>
|
|
Using cells from the mouse model of Mounkes et al. (2005), Ho et al. (2013) found that Lmna N195K embryonic fibroblasts and bone marrow-derived mesenchymal stem cells had impaired nuclear localization of the mechanosensitive transcription factor MKL1 (606078). Cardiac sections from Lmna(N195K/N195K) mice had significantly reduced fractions of cardiomyocytes with nuclear Mkl1, implicating altered Mkl1 signaling in the development of cardiomyopathy in these animals. Nuclear accumulation of Mkl1 was substantially lower in Lmna N195K cells than in wildtype cells. Altered nucleocytoplasmic shuttling of Mkl1 was caused by altered actin dynamics in Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin (300384) restored Mkl1 nuclear translocation and rescued actin dynamics in mutant cells. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, GLU203GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933092,
|
|
|
|
|
|
|
|
ClinVar: RCV000015573, RCV000057428, RCV000211791, RCV003581565
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; 115200), Fatkin et al. (1999) identified a 608A-G transition in the LMNA gene, resulting in a glu203-to-gly (E203G) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG571SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338938,
|
|
|
|
|
|
gnomAD: rs80338938,
|
|
|
|
|
|
ClinVar: RCV000015574, RCV000057044, RCV000705473, RCV001189216, RCV003993745, RCV004018634, RCV004786264
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant dilated cardiomyopathy and conduction defects (CMD1A; 115200), Fatkin et al. (1999) identified a 1711C-A transversion in the LMNA gene, resulting in an arg571-to-ser (R571S) substitution. In this family, the C-terminal of lamin C was selectively affected by the mutation, and the cardiac phenotype was relatively milder than that associated with mutations in the rod domain of the LMNA gene. Furthermore, there was subclinical evidence of involvement of skeletal muscle. Although affected members of this family had no skeletal muscle symptoms, some had elevated serum creatine kinase levels, including 1 asymptomatic family member with the genotype associated with the disease. The arg571-to-ser mutation affected only lamin C isoforms, whereas previously described defects causing Emery-Dreifuss muscular dystrophy (181350) perturbed both lamin A and lamin C isoforms. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
EMERY-DREIFUSS MUSCULAR DYSTROPHY 3, AUTOSOMAL RECESSIVE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG482GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs11575937,
|
|
|
|
|
|
|
|
ClinVar: RCV000015575, RCV000041318, RCV000057299, RCV000190399, RCV000459624, RCV000754814, RCV000763258, RCV001179839, RCV001822996, RCV002390111, RCV004532361, RCV004806012
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 probands from 5 Canadian kindreds with familial partial lipodystrophy of the Dunnigan type (FPLD2; 151660), Cao and Hegele (2000) demonstrated heterozygosity for a G-to-A transition in exon 8 of the LMNA gene, predicted to result in an arg484-to-gln (R482Q) substitution. There were no differences in age, gender, or body mass index in Q482/R482 heterozygotes compared with R482/R482 homozygotes (normals) from these families; however, there were significantly more Q482/R482 heterozygotes who had definite partial lipodystrophy and frank diabetes. Also compared with the normal homozygotes, heterozygotes had significantly higher serum insulin and C-peptide (see 176730) levels. The LMNA heterozygotes with diabetes were significantly older than heterozygotes without diabetes. </p><p>Shackleton et al. (2000) found the R482Q mutation in a family with familial partial lipodystrophy. Hegele et al. (2000) analyzed the relationship between plasma leptin (164160) and the rare LMNA R482Q mutation in 23 adult familial partial lipodystrophy (FPLD) subjects compared with 25 adult family controls with normal LMNA in an extended Canadian FPLD kindred. They found that the LMNA Q482/R482 genotype was a significant determinant of plasma leptin, the ratio of plasma leptin to body mass index (BMI), plasma insulin, and plasma C peptide, but not BMI. Family members who were Q482/R482 heterozygotes had significantly lower plasma leptin and leptin:BMI ratio than unaffected R482/R482 homozygotes. Fasting plasma concentrations of insulin and C peptide were both significantly higher in LMNA Q482/R482 heterozygotes than in R482/R482 homozygotes. Multivariate regression analysis revealed that the LMNA R482Q genotype accounted for 40.9%, 48.2%, 86.9%, and 81.0%, respectively, of the attributable variation in log leptin, leptin:BMI ratio, log insulin, and log C peptide. The authors concluded that a rare FPLD mutation in LMNA determines the plasma leptin concentration. </p><p>Boguslavsky et al. (2006) found that overexpression of wildtype LMNA or mutant R482Q or R482W (150330.0011) in mouse 3T3-L1 preadipocytes prevented cellular lipid accumulation, inhibited triglyceride synthesis, and prevented normal differentiation into adipocytes. In contrast, embryonic fibroblasts from Lmna-null mice had increased levels of basal triglyceride synthesis and differentiated into fat-containing cells more readily that wildtype mouse cells. Mutations at residue 482 are not predicted to affect the structure of the nuclear lamina, but may change interactions with other proteins. The findings of this study suggested that mutations responsible for FPLD are gain-of-function mutations. Boguslavsky et al. (2006) postulated that mutations that result in gain of function may cause higher binding affinity to a proadipogenic transcription factor, thus preventing it from activating target genes; overexpression of the wildtype protein may result in increased numbers of molecules with a normal binding affinity. Overexpression of Lmna was associated with decreased levels of PPARG2 (601487), a nuclear hormone receptor transcription factor putatively involved in adipogenic conversion. Lmna-null cells had increased basal phosphorylation of AKT1 (164730), a mediator of insulin signaling. </p><p>In affected members of a Hutterite family with FPLD2, Wiltshire et al. (2013) identified a heterozygous R482Q mutation. Two family members were homozygous for the mutation and presented with onset of autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; 616516) as well as partial lipodystrophy in the first or second decades. The findings expanded the phenotype associated with this mutation. The overall frequency of the mutation in Dariusleut and Lehrerleut Hutterites in Alberta, Canada, was found to be 1.45%. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
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<div>
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG482TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs57920071,
|
|
|
|
|
|
gnomAD: rs57920071,
|
|
|
|
|
|
ClinVar: RCV000015579, RCV000057298, RCV001174239, RCV001235764, RCV001248961, RCV002390112, RCV002482872, RCV004532362
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 6 families and 3 isolated cases of partial lipodystrophy (FPLD2; 151660), Shackleton et al. (2000) found heterozygosity for C-to-T transition in the LMNA gene, resulting in an arg482-to-trp (R482W) substitution. This is the same codon as that affected in the R482Q mutation (150330.0010). R482L (150330.0012) is a third mutation in the same codon causing partial lipodystrophy. </p><p>Schmidt et al. (2001) identified a family with partial lipodystrophy carrying the R482W mutation in the LMNA gene. Clinically, the loss of subcutaneous fat and muscular hypertrophy, especially of the lower extremities, started as early as in childhood. Acanthosis and severe hypertriglyceridemia developed later in life, followed by diabetes. Characterization of the lipoprotein subfractions revealed that affected children present with hyperlipidemia. The presence and severity of hyperlipidemia seem to be influenced by age, apolipoprotein E genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipidemia is an early and prominent feature in the presented lipodystrophic family carrying the R482W mutation. </p><p>Vadrot et al. (2015) stated that R482 is located within the Ig fold common to A-type lamins, and found that the Ig fold is involved in binding of A-type lamins to SREBP1. In overexpression studies in primary human preadipocytes and patient fibroblasts, Vadrot et al. (2015) found that the R482W substitution reduced the inhibitory interaction of mutant LMNA with SREBP1. R482W patient fibroblasts showed elevated SREBP1 transcriptional activity and derepression of a large number of SREBP1 target genes. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0012 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG482LEU
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<br />
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SNP: rs11575937,
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ClinVar: RCV000015580, RCV000057300, RCV001097055, RCV001097056, RCV001098782, RCV001098783, RCV001098784, RCV001098785, RCV001098786, RCV001098787, RCV001098788
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with partial lipodystrophy (FPLD2; 151660), Shackleton et al. (2000) found that the affected individuals were heterozygous for a G-to-T transversion in the LMNA gene, resulting in an arg482-to-leu (R482L) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0013 CARDIOMYOPATHY, DILATED, 1A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, 1-BP DEL, 959T
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<br />
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SNP: rs56771886,
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ClinVar: RCV000015581, RCV000057492, RCV000681609
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large family with a severe autosomal dominant dilated cardiomyopathy with conduction defects (CMD1A; 115200) in which the majority of affected family members showed signs of mild skeletal muscle involvement, Brodsky et al. (2000) demonstrated heterozygosity in affected members for a 1-bp deletion (del959T) deletion in exon 6 of the LMNA gene. One individual had a pattern of skeletal muscle involvement that the authors considered consistent with mild Emery-Dreifuss muscular dystrophy (EDMD2; 181350). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0014 EMERY-DREIFUSS MUSCULAR DYSTROPHY 3, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, HIS222TYR
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<br />
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SNP: rs28928901,
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ClinVar: RCV000015583, RCV000057440, RCV004577319
|
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|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 40-year-old man with autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; 616516), Raffaele di Barletta et al. (2000) found a homozygous 664C-T transition in the LMNA gene, resulting in a his222-to-tyr (H222Y) amino acid substitution. Both parents, who were first cousins, were heterozygous for the mutation and were unaffected. The mutation was not found among 200 control chromosomes. The patient was the only one with a homozygous LMNA mutation among a larger study of individuals with autosomal dominant Emery-Dreifuss muscular dystrophy. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, GLY465ASP
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<br />
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|
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SNP: rs61282106,
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|
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|
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ClinVar: RCV000015584, RCV000057287, RCV001851878
|
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|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Speckman et al. (2000) found that 1 of 15 families with familial partial lipodystrophy of the Dunnigan variety (FPLD2; 151660) harbored a gly465-to-asp (G465D) mutation in exon 8 of the LMNA gene. </p><p>Simon et al. (2013) noted that G465 is located at the 'bottom front' of the Ig-fold of the mature lamin A tail. They found that the G465D substitution reduced SUMO1 (601912), but not SUMO2 (603042), modification of the lamin A tail in vitro and in cells. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
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LMNA, ARG582HIS
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|
<br />
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|
|
SNP: rs57830985,
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|
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|
|
|
gnomAD: rs57830985,
|
|
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|
|
|
ClinVar: RCV000015585, RCV000057353, RCV001068657, RCV001804734, RCV002399327, RCV003996099, RCV004532363, RCV004795416
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with an atypical form of familial partial lipodystrophy (FPLD2; 151660), Speckman et al. (2000) identified an arg582-to-his (R582H) mutation in exon 11 of the LMNA gene. In a follow-up of this same family, Garg et al. (2001) reported that 2 affected sisters showed less severe loss of subcutaneous fat from the trunk and extremities with some retention of fat in the gluteal region and medial parts of the proximal thighs compared to women with typical FPLD2. Noting that the R582H mutation interrupts only the lamin A protein, Garg et al. (2001) suggested that in typical FPLD2, interruption of both lamins A and C causes a more severe phenotype than that seen in atypical FPLD2, in which only lamin A is altered. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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</div>
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|
|
</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG377HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61672878,
|
|
|
|
|
|
gnomAD: rs61672878,
|
|
|
|
|
|
ClinVar: RCV000057235, RCV000503996, RCV000547164, RCV000681569, RCV001089610, RCV002321484, RCV003319170, RCV005042056
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family (family C) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; 181350) by Straub et al. (2018), Muchir et al. (2000) found a G-to-A transition in exon 6 of the LMNA gene, resulting in a substitution of histidine for arginine-377 (R377H). This family was previously reported by van der Kooi et al. (1996, 1997). </p><p>Taylor et al. (2003) identified heterozygosity for the R377H mutation in an American family of British descent with autosomal dominant dilated cardiomyopathy and mild limb-girdle muscular disease. </p><p>Charniot et al. (2003) described a French family with autosomal dominant severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias and a skeletal muscular dystrophy of the quadriceps muscles. Affected members were found to carry the R377H mutation, which was shown by transfection experiments in both muscular and nonmuscular cells to lead to mislocalization of both lamin and emerin (300384). Unlike previously reported cases of LMNA mutations causing dilated cardiomyopathy with neuromuscular involvement, cardiac involvement preceded neuromuscular disease in all affected members. Charniot et al. (2003) suggested that factors other than the R377H mutation influenced phenotypic expression in this family. Sebillon et al. (2003) also reported on this family. </p><p>In a German woman who had been diagnosed with LGMD1B, Rudnik-Schoneborn et al. (2007) identified a heterozygous R377H mutation in the LMNA gene. Family history revealed that the patient's paternal grandmother had proximal muscle weakness and died from heart disease at age 52, and a paternal aunt had 'walking difficulties' since youth. The patient's father and 4 cousins all had cardiac disease without muscle weakness ranging from nonspecific 'heart attacks' to dilated cardiomyopathy and arrhythmia. The only living affected cousin also carried the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, 3-BP DEL, EXON 3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607540,
|
|
|
|
|
|
|
|
ClinVar: RCV000015588, RCV000057433
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family (family A) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; 181350) by Straub et al. (2018), Muchir et al. (2000) found a 3-bp deletion (AAG) in exon 3 of the LMNA gene, resulting in loss of the codon for lysine-208 (delK208). This family was previously reported by van der Kooi et al. (1996, 1997). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, IVS9DS, G-C, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607539,
|
|
|
|
|
|
|
|
ClinVar: RCV000015589, RCV000057336, RCV002390205
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family (family B) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; 181350) by Straub et al. (2018), Muchir et al. (2000) found a G-to-C transversion in the splice donor site of intron 9, leading to retention of intron 9 and a frameshift at position 536. This potentially results in a truncated protein lacking half of the globular tail domain of lamins A/C. This family was previously reported by van der Kooi et al. (1996, 1997). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2B1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG298CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs59885338,
|
|
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|
|
|
gnomAD: rs59885338,
|
|
|
|
|
|
ClinVar: RCV000015590, RCV000057479, RCV000653885, RCV000826146, RCV000986429, RCV001176301, RCV002467495, RCV003162253, RCV003996100, RCV005042057
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>De Sandre-Giovannoli et al. (2002) found a homozygous arg298-to-cys (R298C) mutation in the LMNA gene in affected members of Algerian families with axonal Charcot-Marie-Tooth disease type 2B1 (CMT2B1; 605588). </p><p>Ben Yaou et al. (2007) identified a homozygous R298C mutation in a female and 2 male affected members of an Algerian family with CMT2B1. The 2 males also had X-linked Emery-Dreifuss muscular dystrophy (310300) and a hemizygous mutation in the EMD gene (300384). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
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</div>
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|
|
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG527HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs57520892,
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|
|
|
|
|
gnomAD: rs57520892,
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|
|
|
|
|
ClinVar: RCV000015591, RCV000015592, RCV000057326, RCV000148607, RCV000555364, RCV001174240, RCV001178367, RCV002399328, RCV003996101, RCV005042058
|
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|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 consanguineous Italian families, Novelli et al. (2002) demonstrated that individuals with mandibuloacral dysplasia (MADA; 248370) were homozygous for an arg527-to-his (R527H) mutation. </p><p>In affected members from 2 pedigrees with MADA, Simha et al. (2003) identified the homozygous R527H mutation. </p><p>In a Mexican American boy with MADA born of related parents, Shen et al. (2003) identified homozygosity for the R527H mutation. The authors noted that all the patients reported by Novelli et al. (2002) shared a common disease haplotype, but that the patients reported by Simha et al. (2003) and their Mexican American patient had different haplotypes, indicating independent origins of the mutation. The mutation is located within the C-terminal immunoglobulin-like domain in the center of a beta sheet on the domain surface of the protein. </p><p>Lombardi et al. (2007) identified this mutation in compound heterozygosity with another missense mutation (V440M; 150330.0044) in a patient with an apparent MADA phenotype associated with muscular hyposthenia and generalized hypotonia. </p><p>Garavelli et al. (2009) reported 2 unrelated patients with early childhood onset of MADA features associated with a homozygous R527H mutation. One presented at age 5 years, 3 months with bulbous distal phalanges of fingers and was observed to have dysmorphic craniofacial features, lipodystrophy type A, and acroosteolysis. The second child, born of consanguineous Pakistani parents, presented at age 4 years, 2 months with a round face, chubby cheeks, thin nose, lipodystrophy type A, and short, broad distal phalanges. Garavelli et al. (2009) emphasized that features of this disorder may become apparent as early as preschool age and that bulbous fingertips may be a clue to the diagnosis. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HUTCHINSON-GILFORD PROGERIA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
RESTRICTIVE DERMOPATHY 2, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, GLY608GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs58596362,
|
|
|
|
|
|
gnomAD: rs58596362,
|
|
|
|
|
|
ClinVar: RCV000015593, RCV000057364, RCV000150957, RCV000806737, RCV001847608
|
|
|
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Hutchinson-Gilford Progeria Syndrome</em></strong></p><p>
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In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (HGPS; 176670), Eriksson et al. (2003) found an identical de novo 1824C-T transition, resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and results in activation of a cryptic splice site and deletion of 50 codons of prelamin A. This mutation was not identified in any of the 16 parents available for testing. </p><p>De Sandre-Giovannoli et al. (2003) identified the exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del) 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>Cao and Hegele (2003) confirmed the observations of Eriksson et al. (2003) using the same cell lines. They referred to this mutation as 2036C-T. </p><p>D'Apice et al. (2004) confirmed paternal age effect and demonstrated a paternal origin of the 2036C-T mutation in 3 families with isolated cases of Hutchinson-Gilford progeria. </p><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. Introduction of LA delta-50 into normal cells by transfection or protein injection induced the same changes. Goldman et al. (2004) hypothesized that the alterations in nuclear structure are due to a concentration-dependent dominant-negative effect of LA delta-50, leading to the disruption of lamin-related functions ranging from the maintenance of nuclear shape to regulation of gene expression and DNA replication. </p><p>In a patient with Hutchinson-Gilford progeria, Wuyts et al. (2005) identified the G608G mutation. 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 manifestations of HGPS. </p><p>Glynn and Glover (2005) studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and G608G-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>In cells from a female patient with HGPS due to the 1824C-T mutation, Shumaker et al. (2006) found that the inactive X chromosome showed loss of histone H3 trimethylation of lys27 (H3K27me3), a marker for facultative heterochromatin, as well as loss of histone H3 trimethylation of lys9 (H3K9me3), a marker of pericentric constitutive heterochromatin. Other alterations in epigenetic control included downregulation of the EZH2 methyltransferase (601573), upregulation of pericentric satellite III repeat transcripts, and increase in the trimethylation of H4K20. The epigenetic alterations were observed before the pathogenic changes in nuclear shape. The findings indicated that the mutant LMNA protein alters sites of histone methylation known to regulate heterochromatin and provided evidence that the rapid aging phenotype of HGPS reflects aspects of normal aging at the molecular level. </p><p>Moulson et al. (2007) demonstrated that HGPS cells with the common 1824C-T LMNA mutation produced about 37.5% of wildtype full-length transcript, which was higher than previous estimates (Reddel and Weiss, 2004). </p><p>Using real-time RT-PCR, Rodriguez et al. (2009) found that progerin transcripts were expressed in dermal fibroblasts cultured from normal controls, but at a level more than 160-fold lower than that detected in dermal fibroblasts cultured from HGPS patients. The level of progerin transcripts, but not of lamin A or lamin C transcripts, increased in late-passage cells from both normal controls and HGPS patients. </p><p><strong><em>Restrictive Dermopathy 2</em></strong></p><p>
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|
In an infant (P2) with restrictive dermopathy (RSDM2; 619793), Navarro et al. (2004) identified the 1824C-T transition in the LMNA gene in heterozygous state. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0023 HUTCHINSON-GILFORD PROGERIA SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, GLY608SER
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<br />
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SNP: rs61064130,
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gnomAD: rs61064130,
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ClinVar: RCV000015595, RCV000057363
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Hutchinson-Gilford progeria syndrome (HGPS; 176670), Eriksson et al. (2003) identified a G-to-A transition in the LMNA gene resulting in a gly-to-ser substitution at codon 608 (G608S). This mutation was not identified in either parent. </p><p>Cao and Hegele (2003) confirmed the observation of Eriksson et al. (2003) using the same cell line. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0024 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, GLU145LYS
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<br />
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SNP: rs60310264,
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ClinVar: RCV000015596, RCV000057406, RCV000192009
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with somewhat atypical features of Hutchinson-Gilford progeria syndrome (HGPS; 176670), Eriksson et al. (2003) identified a glu-to-lys substitution at codon 145 (E145K) in exon 2 of the LMNA gene. This mutation was not identified in either parent. Atypical clinical features, including persistence of coarse hair over the head, ample subcutaneous tissue over the arms and legs, and severe strokes beginning at age 4, may subtly distinguish this phenotype from classic HGPS. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0025 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG471CYS
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<br />
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SNP: rs28928902,
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gnomAD: rs28928902,
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ClinVar: RCV000015597, RCV000057293, RCV001246687
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with an apparently typical progeria phenotype (176670) 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. One mutation, arg471 to cys (R471C), resulted from a 1623C-T transition. An arg527-to-cys (R527C) substitution (150330.0026), resulting from a 1791C-T transition, was found on the other allele. These mutations were not identified in any of 100 control chromosomes. Parental DNA for this patient and a clinical description of the parents were not available. Brown (2004) reported that both he and the patient's physician, Francis Collins, concluded that the patient had mandibuloacral dysplasia (MADA; 248370). </p><p>Zirn et al. (2008) reported a 7-year-old Turkish girl, born of consanguineous parents, who was homozygous for the R471C mutation. She had a phenotype most consistent with an atypical form of MADA, including lipodystrophy, a progeroid appearance, and congenital muscular dystrophy with rigid spine syndrome. These latter features were reminiscent of Emery-Dreifuss muscular dystrophy (181350), although there was no cardiac involvement. She presented at age 10 months with proximal muscle weakness, contractures, spinal rigidity, and a dystrophic skeletal muscle biopsy. Characteristic progeroid features and features of lipodystrophy and mandibuloacral dysplasia were noted at age 3 years and became more apparent with age. Zirn et al. (2008) commented on the severity of the phenotype and emphasized the phenotypic variability in patients with LMNA mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0026 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG527CYS
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<br />
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SNP: rs57318642,
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gnomAD: rs57318642,
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ClinVar: RCV000015576, RCV000057324, RCV000192011, RCV001185736, RCV001223656, RCV002288492, RCV003319169, RCV003996098
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the arg527-to-cys (R527C) mutation in the LMNA gene that was found in compound heterozygous state in a patient with mandibuloacral dysplasia (MADA; 248370) by Cao and Hegele (2003) and Brown (2004), see 150330.0025. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0027 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
|
|
HUTCHINSON-GILFORD PROGERIA SYNDROME, CHILDHOOD-ONSET, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
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LMNA, ARG133LEU
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<br />
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SNP: rs60864230,
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|
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gnomAD: rs60864230,
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|
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ClinVar: RCV000015577, RCV000015578, RCV000057399, RCV001387326
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a male patient whose phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, and hepatic steatosis (FPLD2; 151660), Caux et al. (2003) found a heterozygous 398G-T transversion in exon 2 of the LMNA gene that resulted in an arg-to-leu change at codon 133 (R133L) in the dimerization rod domain of lamins A and C. The patient also had hypertrophic cardiomyopathy with valvular involvement and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadened the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the possibility of hypertrophic cardiomyopathy and skin involvement. </p><p>Vigouroux et al. (2003) emphasized that a striking feature in the patient reported by Caux et al. (2003) was muscular hypertrophy of the limbs, which contrasts with the muscular atrophy usually present in Werner syndrome. Muscular hypertrophy, along with insulin-resistant diabetes and hypertriglyceridemia, is more often associated with LMNA-linked Dunnigan lipodystrophy. Fibroblasts from their patient showed nuclear abnormalities identical to those described in Dunnigan lipodystrophy (Vigouroux et al., 2001). </p><p>In 2 unrelated persons with a progeroid syndrome (see 176670), Chen et al. (2003) found heterozygosity for the R1333L mutation in the LMNA gene. One was a white Portuguese female who presented at the age of 9 years with short stature. She showed scleroderma-like skin changes and graying/thinning of hair. Type 2 diabetes developed at the age of 23 years. Hypogonadism, osteoporosis, and voice changes were also present. The other patient was an African American female in whom the diagnosis of a progeroid syndrome was made at the age of 18 years. Scleroderma-like skin, short stature, graying/thinning of hair, and type 2 diabetes at the age of 18 years were features. The deceased father, paternal aunt, and paternal grandmother of this patient were also diagnosed with severe insulin-resistant diabetes mellitus, suggesting that the R133L mutation might have been paternally inherited. It is noteworthy that a substitution in the same codon, R133P (150330.0032), was reported in a 40-year-old patient with Emery-Dreifuss muscular dystrophy who had disease onset at age 7 years and atrial fibrillation at age 32 years (Brown et al., 2001). Although Chen et al. (2003) designated these patients as having 'atypical Werner syndrome' (277700), Hegele (2003) suggested that the patients more likely had late-onset Hutchinson-Gilford progeria syndrome. </p><p>Jacob et al. (2005) studied the pattern of body fat distribution and metabolic abnormalities in the 2 patients with atypical Werner syndrome described by Chen et al. (2003). Patient 1, an African American female, had normal body fat (27%) by dual energy X-ray absorptiometry (DEXA). However, magnetic resonance imaging (MRI) revealed relative paucity of subcutaneous fat in the distal extremities, with preservation of subcutaneous truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. In contrast, patient 2, a Caucasian female, had only 11.6% body fat as determined by DEXA and had generalized loss of subcutaneous and intraabdominal fat on MRI. She had hypertriglyceridemia and severe insulin-resistant diabetes requiring more than 200 U of insulin daily. Skin fibroblasts showed markedly abnormal nuclear morphology compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. Jacob et al. (2005) concluded that atypical Werner syndrome associated with an R133L mutation in the LMNA gene is phenotypically heterogeneous. Furthermore, the severity of metabolic complications seemed to correlate with the extent of lipodystrophy. </p>
|
|
</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 CARDIOMYOPATHY, DILATED, 1A</strong>
|
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</span>
|
|
</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, GLU161LYS
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<br />
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|
|
SNP: rs28933093,
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|
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gnomAD: rs28933093,
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ClinVar: RCV000015598, RCV000057409, RCV000211788, RCV000687241, RCV001170451, RCV003318333, RCV004018635
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Sebillon et al. (2003) described a family with a history of sudden cardiac death, congestive heart failure, and dilated cardiomyopathy (CMD1A; 115200). Five affected members had a heterozygous 481G-A transition in exon 2 of the LMNA gene, resulting in a glu161-to-lys (E161K) mutation. Dilated cardiomyopathy was present in only 2 patients, in whom onset of the disease was characterized by congestive heart failure and atrial fibrillation (at 29 and 44 years, respectively); heart transplantation was performed in both patients (at 34 and 51 years of age). In the 3 other affected members, the onset of disease was also characterized by atrial fibrillation at 22, 49, and 63 years, but without dilated cardiomyopathy. A 16-year-old male and 12-year-old female were also heterozygous for the mutation, but had no signs or symptoms of heart disease. The 5 affected members were a mother and 2 daughters in 1 branch of the family and 2 brothers in another branch. Two cardiac deaths were reported in the family history: sudden death at 38 years and congestive heart failure at 68 years. No significant atrioventricular block was observed in the family, except in 1 patient for whom cardiac pacing was necessary at 67 years of age because of sinoatrial block coexisting with atrial fibrillation. Sebillon et al. (2003) concluded that the phenotype in this family was characterized by early atrial fibrillation preceding or coexisting with dilated cardiomyopathy, without significant atrioventricular block, and without neuromuscular abnormalities. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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LMNA, 1-BP INS, 28A
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<br />
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|
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SNP: rs57077886,
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|
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ClinVar: RCV000015599, RCV000057387, RCV000502816, RCV000622546, RCV000755005
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Sebillon et al. (2003) described a family in which 5 patients with dilated cardiomyopathy with conduction defects (CMD1A; 115200) were heterozygous for a 1-bp insertion, 28insA, in exon 1 of the LMNA gene. Three additional patients were considered as phenotypically affected with documented dilated cardiomyopathy but were not available for DNA analysis. In the family history, there were 3 cardiac sudden deaths before 55 years of age. In the patients with dilated cardiomyopathy, 3 had associated atrioventricular block requiring pacemaker implantation, 1 had premature ventricular beats leading to a cardioverter defibrillator implantation, and 1 had a mild form of skeletal muscular dystrophy (mild weakness and wasting of quadriceps muscles, as well as myogenic abnormalities on electromyogram). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0030 CARDIOMYOPATHY, DILATED, WITH HYPERGONADOTROPIC HYPOGONADISM</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ALA57PRO
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<br />
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SNP: rs28928903,
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gnomAD: rs28928903,
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ClinVar: RCV000015600, RCV000057349
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In an Iranian female with short stature and a progeroid syndrome (see 176670), Chen et al. (2003) found a heterozygous de novo ala57-to-pro substitution (A57P) resulting from a 584G-C transversion in the LMNA gene. Onset occurred in her early teens, and she was 23 years old at diagnosis. Hypogonadism, osteoporosis, osteosclerosis of digits, and dilated cardiomyopathy were described. Although Chen et al. (2003) designated this patient as having 'atypical Werner syndrome' (277700), Hegele (2003) suggested that the patient more likely had late-onset Hutchinson-Gilford progeria syndrome. </p><p>McPherson et al. (2009) suggested that the patient in whom Chen et al. (2003) identified an A57P LMNA mutation had a distinct phenotype involving dilated cardiomyopathy and hypergonadotropic hypogonadism (212112). </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0031 HUTCHINSON-GILFORD PROGERIA SYNDROME, CHILDHOOD-ONSET</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, LEU140ARG
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<br />
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SNP: rs60652225,
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|
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ClinVar: RCV000015601, RCV000057403
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a white Norwegian male with a progeroid syndrome (see 176670), Chen et al. (2003) found a leu140-to-arg (L140R) substitution resulting from an 834T-G transversion in the LMNA gene. The patient had onset at age 14 of cataracts, scleroderma-like skin, and graying/thinning of hair, as well as hypogonadism, osteoporosis, soft tissue calcification, and premature atherosclerosis. Aortic stenosis and insufficiency were also present. The patient died at the age of 36 years. Although Chen et al. (2003) designated this patient as having 'atypical Werner syndrome' (277700), Hegele (2003) suggested that the patient more likely had late-onset Hutchinson-Gilford progeria syndrome. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0032 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG133PRO
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<br />
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SNP: rs60864230,
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gnomAD: rs60864230,
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ClinVar: RCV000015602, RCV000057398, RCV000686691
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 40-year-old patient with Emery-Dreifuss muscular dystrophy (EDMD2; 181350) who had disease onset at age 7 years and atrial fibrillation at age 32 years, Brown et al. (2001) found an arg133-to-pro (R133P) mutation in the LMNA gene. Chen et al. (2003) noted that the same codon is involved in the arg133-to-leu (150330.0027) mutation in atypical Werner syndrome. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0033 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, LYS542ASN
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<br />
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SNP: rs56673169,
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ClinVar: RCV000015603, RCV000057346
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 4 affected members of a consanguineous family from north India with features of mandibuloacral dysplasia with type A lipodystrophy (MADA; 248370). Plasilova et al. (2004) identified a homozygous 1626G-C transversion in exon 10 of the LMNA gene, resulting in a lys542-to-asn (K542N) substitution. The parents and 1 unaffected daughter were heterozygous for the mutation. Patients in this family showed uniform skeletal malformations such as acroosteolysis of the digits, micrognathia, and clavicular aplasia/hypoplasia, characteristic of mandibuloacral dysplasia. However, the patients also had classic features of Hutchinson-Gilford progeria syndrome (176670). Plasilova et al. (2004) suggested that autosomal recessive HGPS and MADA may represent a single disorder with varying degrees of severity. </p>
|
|
</span>
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|
</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
|
|
</span>
|
|
</h4>
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|
</div>
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<div>
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<span class="mim-text-font">
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LMNA, SER143PHE
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<br />
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SNP: rs58912633,
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|
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ClinVar: RCV000015604, RCV000057405
|
|
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|
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</span>
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|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a young girl with congenital muscular dystrophy and progeroid features (see 613205), Kirschner et al. (2005) identified a 1824C-T transition in the LMNA gene, resulting in a de novo heterozygous missense mutation, ser143 to phe (S143F). The child presented during the first year of life with myopathy with marked axial weakness, feeding difficulties, poor head control and axial weakness. Progeroid features, including growth failure, sclerodermatous skin changes, and osteolytic lesions, developed later. At routine examination at age 8 years, she was found to have a mediolateral myocardial infarction. </p><p>In cultured skin fibroblasts derived from the patient reported by Kirschner et al. (2005), Kandert et al. (2007) found dysmorphic nuclei with blebs and lobulations that accumulated progressively with cell passage. Immunofluorescent staining showed altered lamin A/C organization and aggregate formation. There was aberrant localization of lamin-associated proteins, particularly emerin (EMD; 300384) and nesprin-2 (SYNE2; 608442), which was reduced or absent from the nuclear envelope. However, a subset of mutant cells expressing the giant 800-kD isoform of SYNE2 showed a milder phenotype, suggesting that this isoform exerts a protective effect. Proliferating cells were observed to express the 800-kD SYNE2 isoform, whereas nonproliferating cells did not. In addition, mutant cells showed defects in the intranuclear organization of acetylated histones and RNA polymerase II compared to control cells. The findings indicated that the S143F mutant protein affects nuclear envelope architecture and composition, chromatin organization, gene expression, and transcription. The findings also implicated nesprin-2 as a structural reinforcer at the nuclear envelope. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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|
|
</div>
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|
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<div>
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|
|
|
<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
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LMNA, TYR259TER
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|
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<br />
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SNP: rs58048078,
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gnomAD: rs58048078,
|
|
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|
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ClinVar: RCV000015605, RCV000057457, RCV005089263
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 9 affected members of Dutch family diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was later reclassified as Emery-Dreifuss muscular dystrophy (EDMD2; 181350) by Straub et al. (2018), van Engelen et al. (2005) identified a 777T-A transversion in the LMNA gene, resulting in a tyr259-to-ter substitution (Y259X). The heterozygous Y259X mutation led to a classic LGMD1B phenotype. One infant homozygous for the mutation was born of consanguineous parents who were both affected, and delivered at 30 weeks' gestational age by cesarean section because of decreasing cardiac rhythm. The infant died at birth from very severe generalized muscular dystrophy. Cultured skin fibroblasts from the infant showed complete absence of A-type lamins leading to disorganization of the lamina, alterations in the protein composition of the inner nuclear membrane, and decreased life span. Van Engelen et al. (2005) noted that the fibroblasts from this child showed remarkable similarity, in nuclear architectural defects and in decreased life span, to the fibroblasts of homozygous LMNA (L530P/L530P) mice (Mounkes et al., 2003). </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 RESTRICTIVE DERMOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
HUTCHINSON-GILFORD PROGERIA SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
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|
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|
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<div>
|
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<span class="mim-text-font">
|
|
|
|
LMNA, IVS11DS, G-A, +1
|
|
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|
|
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<br />
|
|
|
|
SNP: rs113436208,
|
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|
|
|
|
|
ClinVar: RCV000015607, RCV000057377, RCV001847645
|
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Restrictive Dermopathy 2</em></strong></p><p>
|
|
In a premature infant (P1) who died at 6 months of age due to restrictive dermopathy (RSDM2; 619793), Navarro et al. (2004) identified a heterozygous G-to-A transition at position 1 in the intron 11 donor site of the LMNA gene (IVS11+1G-A), resulting in loss of exon 11 from the transcript. The patient expressed lamins A and C and a truncated prelamin A. Patient cells showed an abnormal transcript with an in-frame deletion of the entire exon 11 (270 bp), predicted to cause an internal deletion of 90 residues corresponding to a large part of the globular domain (Gly567_Gln656del). </p><p>Barthelemy et al. (2015) analyzed LMNA exon 11 transcripts in cells derived from the patient reported by Navarro et al. (2004). In addition to production of a normal full-length prelamin A transcript, there was a band corresponding to prelamin A(del50) (progerin), and an additional transcript correlation to prelamin A(del90) resulting from the skipping of all of exon 11. The prelamin A(del90) transcript was termed 'dermopathin.' </p><p><strong><em>Hutchinson-Guilford Progeria Syndrome</em></strong></p><p>
|
|
In a patient with an extremely severe form of Hutchinson-Guilford progeria syndrome (HGPS; 176670), Moulson et al. (2007) identified a heterozygous G-to-A transition at the +1 position of the donor splice site of intron 11 in the LMNA gene (1968+1G-A). RT-PCR studies showed a truncated protein product identical to that observed in HGPS cell lines with the common 1824C-T mutation (150330.0022), indicating that the new mutation resulted in the abnormal use of the same cryptic exon 11 splice site. The findings were in contrast to those reported by Navarro et al. (2004), who observed skipping of exon 11 with 1968+1G-A. Further quantitative studies of the patient's cells by Moulson et al. (2007) found a 4.5-fold increase in the relative ratio of mutant mRNA and protein to wildtype prelamin A compared to typical HGPS cells. The findings were confirmed by Western blot analysis and provided an explanation for the severe phenotype observed in this patient. He had had abnormally thick and tight skin observed at 11 weeks of age, and developed more typical but severe progeroid features over time. He died of infection at age 3.5 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ALA529VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs60580541,
|
|
|
|
|
|
|
|
ClinVar: RCV000015608, RCV000057332, RCV002399329, RCV002467496, RCV003234906
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Turkish patients with mandibuloacral dysplasia with type A lipodystrophy (MADA; 248370), a 21-year-old woman previously described by Cogulu et al. (2003) and an 18-year-old man, Garg et al. (2005) identified homozygosity for a 1586C-T transition in the LMNA gene, resulting in an ala529-to-val (A529V) substitution. Intragenic SNPs revealed a common haplotype spanning 2.5 kb around the mutated nucleotide in the parents of both patients, suggesting ancestral origin of the mutation. The female patient had no breast development despite normal menstruation, a phenotype different from that seen in women with the R527H mutation (150330.0021). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, GLN493TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs56699480,
|
|
|
|
|
|
|
|
ClinVar: RCV000015609, RCV000057304, RCV004698335
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German woman diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy by Straub et al. (2018), Rudnik-Schoneborn et al. (2007) identified a heterozygous 1477C-T transition in exon 8 of the LMNA gene, resulting in a gln493-to-ter (Q493X) substitution. She presented with slowly progressive proximal muscle weakness beginning in the lower extremities and later involving the upper extremities. EMG showed both neurogenic and myopathic defects in the quadriceps muscle. At age 53 years, she was diagnosed with atrioventricular conduction block and arrhythmia requiring pacemaker implantation. Family history showed that her mother had walking difficulties from age 40 years and died of a heart attack at age 54. Six other deceased family members had suspected cardiomyopathy without muscle involvement. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, IVS8DS, G-C, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607543,
|
|
|
|
|
|
|
|
ClinVar: RCV000015610, RCV000057307, RCV003581575
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Morel et al. (2006) reported 2 sisters, the children of nonconsanguineous Punjabi parents, with familial partial lipodystrophy type 2 (FPLD2; 151660). The first presented with acanthosis nigricans at age 5 years, diabetes with insulin resistance, hypertension, and hypertriglyceridemia at age 13 years, and partial lipodystrophy starting at puberty. Her sister and their mother had a similar metabolic profile and physical features, and their mother died of vascular disease at age 32 years. LMNA sequencing showed that the sisters were each heterozygous for a novel G-to-C mutation at the intron 8 consensus splice donor site, which was absent from the genomes of 300 healthy individuals. The retention of intron 8 in mRNA predicted a prematurely terminated lamin A isoform (516 instead of 664 amino acids) with 20 nonsense 3-prime terminal residues. The authors concluded that this was the first LMNA splicing mutation to be associated with FPLD2, and that it causes a severe clinical and metabolic phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 HUTCHINSON-GILFORD PROGERIA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, VAL607VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs59886214,
|
|
|
|
|
|
|
|
ClinVar: RCV000015611, RCV000057362
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a severe form of Hutchinson-Gilford progeria syndrome (HGPS; 176670), Moulson et al. (2007) identified a de novo heterozygous 1821G-A transition in exon 11 of the LMNA gene, resulting in a val607-to-val (V607V) substitution. The 1821G-A mutation favored the use of the same cryptic splice site as the common 1824C-T mutation (150330.0022) and produced the same resultant progerin product. However, the ratio of mutant to wildtype mRNA and protein was increased in the patient compared to typical HGPS cells. The patient had flexion contractures, thick and tight skin, and other severe progeroid features. He died of infection at 26 days of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL, INCLUDED<br />
|
|
LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, SER573LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs60890628,
|
|
|
|
|
|
gnomAD: rs60890628,
|
|
|
|
|
|
ClinVar: RCV000015612, RCV000015613, RCV000015614, RCV000041329, RCV000057351, RCV000617932, RCV000653881, RCV001188887, RCV001248900, RCV002221478, RCV002509159, RCV005042059
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 50-year-old Italian woman with sporadic dilated cardiomyopathy with conduction defects (CMD1A; 115200), Taylor et al. (2003) identified heterozygosity for a 1718C-T transition in exon 11 of the LMNA gene, resulting in a ser573-to-leu substitution at a highly conserved residue, predicted to affect the carboxyl tail of the lamin A isoform. The mutation was not found in the proband's 2 unaffected offspring or in 300 control chromosomes, but her unaffected 60-year-old sister also carried the mutation. </p><p>Van Esch et al. (2006) analyzed the LMNA gene in a 44-year-old male of European descent with arthropathy, tendinous calcifications, and a progeroid appearance (see 248370) and identified homozygosity for the S573L mutation. Progeroid features included a small pinched nose, small lips, micrognathia with crowded teeth, cataract, and alopecia. He also had generalized lipodystrophy, and sclerodermatous skin. The arthropathy affected predominantly the distal femora and proximal tibia in the knee with tendinous calcifications. However, he had normal clavicles and no evidence of acroosteolysis. The authors concluded that he had a novel phenotype. The patient's unaffected 15-year-old son was heterozygous for the mutation, which was not found in 450 control chromosomes. The authors noted that the patient had no evidence of cardiomyopathy and his 70-year-old mother, an obligate heterozygote, had no known cardiac problems. </p><p>In a 75-year-old European male with partial lipodystrophy (FPLD2; 151660), Lanktree et al. (2007) identified heterozygosity for the S573L mutation in the LMNA gene. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0042 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ASP230ASN
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<br />
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SNP: rs61214927,
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ClinVar: RCV000015615, RCV000057443
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 46-year-old South Asian female with partial lipodystrophy (FPLD2; 151660), Lanktree et al. (2007) identified heterozygosity for a 688G-A transition in exon 4 of the LMNA gene, resulting in an asp230-to-asn (D230N) substitution at a conserved residue located 5-prime to the nuclear localization signal. The mutation, predicted to affect only the lamin A isoform, was not found in 200 controls of multiple ethnic backgrounds. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0043 LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG399CYS
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<br />
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SNP: rs58672172,
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gnomAD: rs58672172,
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ClinVar: RCV000015616, RCV000057255, RCV000653937, RCV001174241, RCV001188431, RCV001257937, RCV002336085, RCV005042060
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 50-year-old European female with partial lipodystrophy (FPLD2; 151660), Lanktree et al. (2007) identified heterozygosity for a 1195C-T transition in exon 7 of the LMNA gene, resulting in an arg399-to-cys (R399C) substitution at a conserved residue located 5-prime to the nuclear localization signal. The mutation, predicted to affect only the lamin A isoform, was not found in 200 controls of multiple ethnic backgrounds. </p><p>Decaudain et al. (2007) identified a heterozygous R399 mutation in a woman with severe metabolic syndrome. She was diagnosed with insulin-resistant diabetes at age 32. Chronic hyperglycemia led to retinopathy, peripheral neuropathy, and renal failure. She had severe hypertriglyceridemia and diffuse atherosclerosis, requiring coronary artery bypass at age 49. Physical examination revealed android fat distribution with lipoatrophy of lower limbs and calves hypertrophy without any muscle weakness. Her mother and a brother had diabetes and died several years earlier. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0044 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, ATYPICAL</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, VAL440MET
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<br />
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SNP: rs121912493,
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ClinVar: RCV000015617, RCV000057268, RCV000552191, RCV001172618, RCV001186220, RCV001264435, RCV002381252, RCV003996102, RCV005049339
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 27-year-old Italian woman with a mandibuloacral dysplasia type A (MADA; 248370)-like phenotype, Lombardi et al. (2007) found compound heterozygosity for missense mutations in the LMNA cDNA: a G-to-A transition at position 1318 in exon 7 that gave rise to a val-to-met substitution at codon 440 (V440M), and an R527H substitution (150330.0021). Each healthy parent was a simple heterozygote for one or the other mutation. The apparent MADA phenotype was associated with muscular hyposthenia and generalized hypotonia. Clavicular hypoplasia and metabolic imbalances were absent. Lombardi et al. (2007) hypothesized that lack of homozygosity for the R527H mutation attenuated the MADA phenotype, while the V440M mutation may have contributed to both the muscle phenotype and the pathogenic effect of the single R527H mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0045 HEART-HAND SYNDROME, SLOVENIAN TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, IVS9AS, T-G, -12
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<br />
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SNP: rs267607582,
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gnomAD: rs267607582,
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ClinVar: RCV000015618, RCV000057337
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Slovenian family with heart-hand syndrome (610140), originally reported by Sinkovec et al. (2005), Renou et al. (2008) identified heterozygosity for a T-G transversion in intron 9 of the LMNA gene (IVS9-12T-G), predicted to cause a frameshift and premature termination in exon 10, with the addition of 14 new amino acids at the C terminus. The mutation was not found in unaffected family members or in 100 healthy controls. Analysis of fibroblasts from 2 affected individuals confirmed the presence of truncated protein and revealed aberrant localization of lamin A/C accumulated in intranuclear foci as well as dysmorphic nuclei with nuclear envelope herniations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0046 MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY</strong>
|
|
</span>
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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LMNA, ALA529THR
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<br />
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SNP: rs121912494,
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gnomAD: rs121912494,
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ClinVar: RCV000015619, RCV000057331
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|
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|
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</span>
|
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In a 56-year-old Japanese woman, born of consanguineous parents, with mandibuloacral dysplasia and type A lipodystrophy (MADA; 248370), Kosho et al. (2007) identified a homozygous 1585G-A transition in exon 9 of the LMNA gene, resulting in an ala529-to-thr (A529T) substitution. The authors stated that she was the oldest reported patient with the disorder. In addition to classic MAD with lipodystrophy type A phenotype, including progeroid appearance, acroosteolysis of the distal phalanges, and loss of subcutaneous fat in the limbs, she had severe progressive destructive skeletal and osteoporotic changes. Vertebral collapse led to paralysis. However, Kosho et al. (2007) also noted that other factors may have contributed to the severe osteoporosis observed in this patient. Another mutation in this codon, A529V (150330.0037), results in a similar phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0047 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
|
|
</span>
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LMNA, LEU380SER
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<br />
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SNP: rs121912495,
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ClinVar: RCV000015620, RCV000057237
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with a LMNA-related congenital muscular dystrophy (613205), Quijano-Roy et al. (2008) identified a de novo heterozygous mutation in exon 6 of the LMNA gene, resulting in a leu380-to-ser (L380S) substitution. He showed decreased movements in utero, hypotonia, talipes foot deformities, no head or trunk control, distal joint contractures, respiratory insufficiency, and paroxysmal atrial tachycardia. Serum creatine kinase was increased, and muscle biopsy showed dystrophic changes. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0048 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
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|
LMNA, ARG249TRP
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<br />
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|
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SNP: rs121912496,
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ClinVar: RCV000015621, RCV000057452, RCV000814531
|
|
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|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old girl with congenital muscular dystrophy (613205), Quijano-Roy et al. (2008) identified a de novo heterozygous mutation in exon 4 of the LMNA gene, resulting in an arg249-to-trp (R249W) substitution. She presented at age 3 to 6 months with axial weakness and talipes foot deformities. She lost head support at 9 months, had respiratory insufficiency, joint contractures, and axial and limb muscle weakness. A de novo heterozygous R249W mutation was also identified in an unrelated 3-year-old boy with congenital LGMD1B who showed decreased movements in utero, hypotonia, distal contractures, no head or trunk control, and respiratory insufficiency. Both patients had increased serum creatine kinase and showed myopathic changes on EMG studies. </p><p>Scharner et al. (2011) found that transfection of the R249W mutation into cells resulted in increased expression of mutant LMNA, mislocalization of the protein in the nucleus, abnormal nuclear morphology with lobules, and mislocalization of lamin B (LMNB; 150340). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0049 EMERY-DREIFUSS MUSCULAR DYSTROPHY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED, INCLUDED
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, GLU358LYS
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs60458016,
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|
|
ClinVar: RCV000015622, RCV000015623, RCV000057227, RCV000470514, RCV000502108, RCV001420791
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mercuri et al. (2004) identified a de novo heterozygous 1072G-A transition in exon 5 of the LMNA gene, resulting in a glu358-to-lys (E358K) substitution, in 5 unrelated patients with muscular dystrophy. Three patients had the common phenotype of autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; 181350), 1 was diagnosed with early-onset limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as EDMD2 by Straub et al. (2018), and the last had had a more severe disorder consistent with congenital muscular dystrophy (613205). The mutation was not identified in 150 controls. The patient with LGMD1B also had cardiac conduction abnormalities, respiratory failure, and features of lipodystrophy (FPLD2; 151660). Mercuri et al. (2004) commented on the extreme phenotypic variability associated with this mutation. </p><p>In 4 unrelated patients with LMNA-related congenital muscular dystrophy, Quijano-Roy et al. (2008) identified a de novo heterozygous mutation in exon 6 of the LMNA gene, resulting in a glu358-to-lys (E358K) substitution. Three patients presented before 1 year of age with hypotonia and later developed head drop with neck muscle weakness. There was delayed motor development with early loss of ambulation, distal limb contractures, axial and limb muscle weakness, respiratory insufficiency requiring mechanical ventilation, increased serum creatine kinase, and dystrophic changes on muscle biopsy. One patient developed ventricular tachycardia at age 20 years. The fourth patient with congenital LGMD1B had decreased fetal movements and presented at age 3 to 6 months with hypotonia, loss of head control, and delayed motor development. </p>
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0050 MUSCULAR DYSTROPHY, CONGENITAL, LMNA-RELATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, 3-BP DEL, 94AAG
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<br />
|
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|
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SNP: rs60872029,
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|
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|
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ClinVar: RCV000015625, RCV000057490, RCV000459386
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 18-month-old boy with LMNA-related congenital muscular dystrophy (613205), D'Amico et al. (2005) identified a de novo heterozygous 3-bp deletion (94delAAG) in exon 1 of the LMNA gene, resulting in the deletion of lys32. Although he had normal early motor development, he showed prominent neck extensor weakness resulting in a 'dropped head' phenotype at age 1 year. He was able to stand independently but had some difficulty walking. </p>
|
|
</span>
|
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</div>
|
|
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<div>
|
|
<br />
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|
</div>
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</div>
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|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0051 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG644CYS
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|
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<br />
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|
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SNP: rs142000963,
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gnomAD: rs142000963,
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ClinVar: RCV000015626, RCV000041340, RCV000057374, RCV000144868, RCV000148602, RCV000245284, RCV000755679, RCV000771143, RCV001084244, RCV001174411, RCV002467497, RCV003224100, RCV004528114
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</span>
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</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to various phenotypes has not been confirmed.</p><p>An arg644-to-cys (R644C) mutation in the LMNA gene has been found in several different phenotypic presentations (Genschel et al., 2001; Mercuri et al., 2005; Rankin et al., 2008), but the pathogenicity of the mutation has not been confirmed (Moller et al., 2009). </p><p>In a German patient with dilated cardiomyopathy with no history of conduction system disease (see 115200), Genschel et al. (2001) identified heterozygosity for a 1930C-T transition in exon 11 of the LMNA gene resulting in an R644C substitution in the C-terminal domain of lamin A. The authors noted that the mutation is solely within lamin A, but not lamin C, whereas previously reported mutations causing dilated cardiomyopathy are located more in the rod domain of the protein. </p><p>Mercuri et al. (2005) identified heterozygosity for the R644C mutation in 4 patients with skeletal and cardiac muscle involvement of varying severity. In 1 patient, the mutation was found in the affected brother and the unaffected father, and was not found in the affected mother. The mutation was not found in 100 unrelated control subjects. </p><p>Rankin et al. (2008) described 9 patients in 8 families with the R644C mutation. Patients 1 and 2 presented with lipodystrophy and insulin resistance; patient 1 also had focal segmental glomerulosclerosis. Patient 3 presented with motor neuropathy, patient 4 with arthrogryposis and dilated cardiomyopathy with left ventricular noncompaction, patient 5 with severe scoliosis and contractures, patient 6 with limb-girdle weakness, and patient 7 with hepatic steatosis and insulin resistance. Patients 8 and 9 were brothers who had proximal weakness and contractures. The same mutation was identified in 9 unaffected individuals in these 9 families, but was not detected in 200 German and 300 British controls. Rankin et al. (2008) suggested that extreme phenotypic diversity and low penetrance are associated with the R644C mutation. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0052 CARDIOMYOPATHY, DILATED, WITH HYPERGONADOTROPIC HYPOGONADISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
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LMNA, LEU59ARG
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<br />
|
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|
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SNP: rs58922911,
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ClinVar: RCV000015627, RCV000057357
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 17-year-old Caucasian female with dilated cardiomyopathy and ovarian failure (212112), Nguyen et al. (2007) identified heterozygosity for a de novo 176T-C transition in exon 1 of the LMNA gene, predicted to result in a leu59-to-arg (L59R) substitution. Analysis of nuclear morphology in patient fibroblasts showed more irregularity and variation than that of control fibroblasts, with denting, blebbing, and irregular margins. The mutation was not found in the unaffected parents or in 116 population-based controls. </p><p>In a 15-year-old Caucasian girl with dilated cardiomyopathy and ovarian failure who died from an arrhythmia while awaiting cardiac transplantation, McPherson et al. (2009) identified heterozygosity for the L59R mutation in the LMNA gene. The mutation was presumed to be de novo, although the unaffected parents declined DNA testing. The patient also had a healthy older sister, and there was no family history of cardiomyopathy or hypogonadism. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0053 CARDIOMYOPATHY, DILATED, 1A</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG541GLY
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<br />
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SNP: rs56984562,
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ClinVar: RCV000022641, RCV000057342
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs with dilated cardiomyopathy (CMD1A; 115200), Malek et al. (2011) identified a heterozygous 1621C-G transversion in exon 10 of the LMNA gene, resulting in an arg541-to-gly (R541G) substitution in the C-terminal tail region. The 23-year-old male proband had a history of paroxysmal atrioventricular nodal reentrant tachycardia and was found by echocardiogram to have dilation of the left ventricle and global hypokinesis. Cardiac MRI showed discrete regional areas of akinesis with muscle thinning in the left ventricle and marked hypertrabeculation in dysfunctional regions, as well as evidence of fibrosis. The proband's sister had sinus bradycardia and supraventricular and ventricular arrhythmias, but normal echocardiogram and cardiac MRI. The sibs' father and paternal aunt had both died of dilated cardiomyopathy. In vitro functional expression studies showed that the R541G mutant resulted in the formation of abnormal lamin aggregates, most of which were sickle-shaped, suggesting aberrant formation of the inner nuclear lamina from misassembled lamin dimers. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0054 EMERY-DREIFUSS MUSCULAR DYSTROPHY 3, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, ARG225GLN
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<br />
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SNP: rs199474724,
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ClinVar: RCV000034134, RCV000190400, RCV001178806, RCV001384595, RCV001781340, RCV001814022, RCV003996150, RCV005042105
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 4 sibs, born of consanguineous Spanish parents, with autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3; 616516), Jimenez-Escrig et al. (2012) identified a homozygous c.674G-A transition in exon 4 of the LMNA gene, resulting in an arg225-to-gln (R225Q) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in 200 control chromosomes. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0055 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, GLN656GLN
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<br />
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SNP: rs797044487,
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ClinVar: RCV000190822, RCV000192015
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 2 sibs and a mother with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; 176670), Hisama et al. (2011) identified a heterozygous c.1968G-A transition at the last nucleotide of exon 11 of the LMNA gene, predicted to result in a nonsynonymous gln656-to-gln (Q656Q) substitution. However, analysis of patient cells showed that the mutation affected splicing, resulting in an in-frame deletion of 150 nucleotides that corresponded to progerin (see 150330.0022) observed in patients with HGPS. The ratio of progerin/lamin A was 0.15, which is one-quarter that observed in HGPS cells. The patients had adult-onset severe coronary artery disease and a progeroid appearance. </p><p>Barthelemy et al. (2015) identified a heterozygous c.1968G-A (c.1968G-A, NM_1707073) transition in the LMNA gene in another patient with adult-onset HGPS manifest as progeroid features and severe atherosclerosis necessitating bypass surgery at age 35. Analysis of LMNA exon 11 transcripts in patient cells showed the production of a normal full-length prelamin A transcript, a band corresponding to prelamin A(del50) (progerin), and an additional transcript corresponding 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). In fibroblasts derived from 2 of the patients reported by Hisama et al. (2011), Barthelemy et al. (2015) presented preliminary evidence that a polymorphism in exon 10 of the LMNA gene (rs4641) may influence the production of various transcripts. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0056 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
|
|
</span>
|
|
</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMNA, IVS11DS, G-A, +5
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<br />
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SNP: rs797044488,
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ClinVar: RCV000190823, RCV000192020
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a woman with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; 176670) manifest as severe coronary artery disease and progeroid features, Hisama et al. (2011) identified a heterozygous G-to-A transition (c.1968+5G-A) in the donor splice site of intron 11 of the LMNA gene, resulting in a 150-bp deletion. Western blot analysis of patient cells showed progerin at lower levels than in classic HGPS patient cells. </p><p>Barthelemy et al. (2015) identified a heterozygous c.1968+5G-A transition (c.1968+5G-A, NM_170707.3) in the LMNA gene in another patient with atypical HGPS manifest as progeroid features and cardiac disease. He died at age 17 years of hypertrophic cardiomyopathy and aortic and mitral valve stenosis. Analysis of LMNA exon 11 transcripts in patient cells showed the production of 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). </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0057 HUTCHINSON-GILFORD PROGERIA SYNDROME, ATYPICAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LMNA, ASP300GLY
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<br />
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SNP: rs79907212,
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ClinVar: RCV000201431
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a family with a protracted form of Hutchinson-Gilford progeria syndrome (HGPS; 176670) manifest as premature cutaneous and cardiac aging, Kane et al. (2013) identified a heterozygous c.899A-G transition in the LMNA gene, resulting in an asp300-to-gly (D300G) substitution at a highly conserved residue in the second coiled-coil domain. The mutation, which segregated with the disorder in the family, was not found in the 1000 Genomes Project (Phase 1) or Exome Variant Server databases or in 100 control chromosomes. The affected domain mediates lamin protein dimerization and promotes filament formation. 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>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0058 HEART-HAND SYNDROME, SLOVENIAN TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNA, ARG335TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs386134243,
|
|
|
|
|
|
gnomAD: rs386134243,
|
|
|
|
|
|
ClinVar: RCV000030145, RCV000182368, RCV000546102, RCV000620788, RCV000721960, RCV000844672, RCV000845456, RCV000852407, RCV001196390, RCV002477025, RCV003149579, RCV003492303, RCV004532421
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Slovenian-type heart-hand syndrome, Zaragoza et al. (2017) identified heterozygosity for a c.1003C-T transition in the LMNA gene, resulting in an arg335-to-trp (R335W) substitution, that segregated with the disorder in the family. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
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<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Krohne and Benavente (1986); Lebel and Raymond (1987)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacene, E., Fromes, Y., Toussaint, M., Mura, A.-M., Keller, D. I., Amthor, H., Isnard, R., Malissen, M., Schwartz, K., Bonne, G.
|
|
<strong>Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.</strong>
|
|
Hum. Molec. Genet. 14: 155-169, 2005.
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[PubMed: 15548545]
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[Full Text: https://doi.org/10.1093/hmg/ddi017]
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</p>
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</li>
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<li>
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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.
|
|
<strong>Truncated prelamin A expression in HGPS-like patients: a transcriptional study.</strong>
|
|
Europ. J. Hum. Genet. 23: 1051-1061, 2015.
|
|
|
|
|
|
[PubMed: 25649378]
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[Full Text: https://doi.org/10.1038/ejhg.2014.239]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Ben Yaou, R., Toutain, A., Arimura, T., Demay, L., Massart, C., Peccate, C., Muchir, A., Llense, S., Deburgreave, N., Leturcq, F., Litim, K. E., Rahmoun-Chiali, N., Richard, P., Babuty, D., Recan-Budiartha, D., Bonne, G.
|
|
<strong>Multitissular involvement in a family with LMNA and EMD mutations: role of digenic mechanism?</strong>
|
|
Neurology 68: 1883-1894, 2007.
|
|
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|
|
[PubMed: 17536044]
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[Full Text: https://doi.org/10.1212/01.wnl.0000263138.57257.6a]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Benedetti, S., Menditto, I., Degano, M., Rodolico, C., Merlini, L., D'Amico, A., Palmucci, L., Berardinelli, A., Pegoraro, E., Trevisan, C. P., Morandi, L., Moroni, I., and 15 others.
|
|
<strong>Phenotypic clustering of lamin A/C mutations in neuromuscular patients.</strong>
|
|
Neurology 69: 1285-1292, 2007.
|
|
|
|
|
|
[PubMed: 17377071]
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[Full Text: https://doi.org/10.1212/01.wnl.0000261254.87181.80]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Boguslavsky, R. L., Stewart, C. L., Worman, H. J.
|
|
<strong>Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 15: 653-663, 2006.
|
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|
|
[PubMed: 16415042]
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[Full Text: https://doi.org/10.1093/hmg/ddi480]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.-M., Hammouda, E.-H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary, F., Urtizberea, J.-A., Duboc, D., Fardeau, M., Toniolo, D., Schwartz, K.
|
|
<strong>Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.</strong>
|
|
Nature Genet. 21: 285-288, 1999.
|
|
|
|
|
|
[PubMed: 10080180]
|
|
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|
|
[Full Text: https://doi.org/10.1038/6799]
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</p>
|
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</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Brodsky, G. L., Muntoni, F., Miocic, S., Sinagra, G., Sewry, C., Mestroni, L.
|
|
<strong>Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement.</strong>
|
|
Circulation 101: 473-476, 2000.
|
|
|
|
|
|
[PubMed: 10662742]
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|
|
[Full Text: https://doi.org/10.1161/01.cir.101.5.473]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Broers, J. L. V., Peeters, E. A. G., Kuijpers, H. J. H., Endert, J., Bouten, C. V. C., Oomens, C. W. J., Baaijens, F. P. T., Ramaekers, F. C. S.
|
|
<strong>Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies.</strong>
|
|
Hum. Molec. Genet. 13: 2567-2580, 2004.
|
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|
|
[PubMed: 15367494]
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|
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[Full Text: https://doi.org/10.1093/hmg/ddh295]
|
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</p>
|
|
</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Brown, C. A., Lanning, R. W., McKinney, K. Q., Salvino, A. R., Cherniske, E., Crowe, C. A., Darras, B. T., Gominak, S., Greenberg, C. R., Grosmann, C., Heydemann, P., Mendell, J. R., Pober, B. R., Sasaki, T., Shapiro, F., Simpson, D. A., Suchowersky, O., Spence, J. E.
|
|
<strong>Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Med. Genet. 102: 359-367, 2001.
|
|
|
|
|
|
[PubMed: 11503164]
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|
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[Full Text: https://doi.org/10.1002/ajmg.1463]
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</p>
|
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</li>
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<li>
|
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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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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Cao, H., Hegele, R. A.
|
|
<strong>Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 9: 109-112, 2000.
|
|
|
|
|
|
[PubMed: 10587585]
|
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|
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[Full Text: https://doi.org/10.1093/hmg/9.1.109]
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</p>
|
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</li>
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<li>
|
|
<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>
|
|
J. Hum. Genet. 48: 271-274, 2003.
|
|
|
|
|
|
[PubMed: 12768443]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-003-0025-3]
|
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|
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Capanni, C., Mattioli, E., Columbaro, M., Lucarelli, E., Parnaik, V. K., Novelli, G., Wehnert, M., Cenni, V., Maraldi, N. M., Squarzoni, S., Lattanzi, G.
|
|
<strong>Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 14: 1489-1502, 2005.
|
|
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|
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[PubMed: 15843404]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi158]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Capell, B. C., Collins, F. S.
|
|
<strong>Human laminopathies: nuclei gone genetically awry.</strong>
|
|
Nature Rev. Genet. 7: 940-952, 2006.
|
|
|
|
|
|
[PubMed: 17139325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nrg1906]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Capell, B. C., Erdos, M. R., Madigan, J. P., Fiordalisi, J. J., Varga, R., Conneely, K. N., Gordon, L. B., Der, C. J., Cox, A. D., Collins, F. S.
|
|
<strong>Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 12879-12884, 2005.
|
|
|
|
|
|
[PubMed: 16129833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0506001102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caux, F., Dubosclard, E., Lascols, O., Buendia, B., Chazouilleres, O., Cohen, A., Courvalin, J.-C., Laroche, L., Capeau, J., Vigouroux, C., Christin-Maitre, S.
|
|
<strong>A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1006-1013, 2003.
|
|
|
|
|
|
[PubMed: 12629077]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021506]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M.
|
|
<strong>Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.</strong>
|
|
Hum. Mutat. 21: 473-481, 2003.
|
|
|
|
|
|
[PubMed: 12673789]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10170]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, C.-Y., Chi, Y.-H., Mutalif, R. A., Starost, M. F., Myers, T. G., Anderson, S. A., Stewart, C. L., Jeang, K.-T.
|
|
<strong>Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.</strong>
|
|
Cell 149: 565-577, 2012.
|
|
|
|
|
|
[PubMed: 22541428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2012.01.059]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<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: 12927431]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(03)14069-X]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Choi, J. C., Wu, W., Muchir, A., Iwata, S., Homma, S., Worman, H. J.
|
|
<strong>Dual specificity phosphatase 4 mediates cardiomyopathy caused by lamin A/C (LMNA) gene mutation.</strong>
|
|
J. Biol. Chem. 287: 40513-40524, 2012.
|
|
|
|
|
|
[PubMed: 23048029]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M112.404541]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Coffinier, C., Hudon, S. E., Farber, E. A., Chang, S. Y., Hrycyna, C. A., Young, S. G., Fong, L. G.
|
|
<strong>HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 13432-13437, 2007.
|
|
|
|
|
|
[PubMed: 17652517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0704212104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cogulu, O., Gunduz, C., Darcan, S., Kadioglu, B., Ozkinay, F., Ozkinay, C.
|
|
<strong>Mandibuloacral dysplasia with absent breast development. (Letter)</strong>
|
|
Am. J. Med. Genet. 119A: 391-392, 2003.
|
|
|
|
|
|
[PubMed: 12784312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.10169]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Csoka, A. B., Cao, H., Sammak, P. J., Constantinescu, D., Schatten, G. P., Hegele, R. A.
|
|
<strong>Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.</strong>
|
|
J. Med. Genet. 41: 304-308, 2004.
|
|
|
|
|
|
[PubMed: 15060110]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2003.015651]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
D'Amico, A., Haliloglu, G., Richard, P., Talim, B., Maugenre, S., Ferreiro, A., Guicheney, P., Menditto, I., Benedetti, S., Bertini, E., Bonne, G., Topaloglu, H.
|
|
<strong>Two patients with 'dropped head syndrome' due to mutations in LMNA or SEPN1 genes.</strong>
|
|
Neuromusc. Disord. 15: 521-524, 2005.
|
|
|
|
|
|
[PubMed: 15961312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2005.03.006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
D'Apice, M. R., Tenconi, R., Mammi, I., van den Ende, J., Novelli, G.
|
|
<strong>Paternal origin of LMNA mutations in Hutchinson-Gilford progeria. (Letter)</strong>
|
|
Clin. Genet. 65: 52-54, 2004.
|
|
|
|
|
|
[PubMed: 15032975]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j..2004.00181.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, B. S. J., Barnes, R. H., II, Tu, Y., Ren, S., Andres, D. A., Spielmann, H. P., Lammerding, J., Wang, Y., Young, S. G., Fong, L. G.
|
|
<strong>An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.</strong>
|
|
Hum. Molec. Genet. 19: 2682-2694, 2010.
|
|
|
|
|
|
[PubMed: 20421363]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq158]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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: 12702809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1084125]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N.
|
|
<strong>Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.</strong>
|
|
Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002.
|
|
|
|
|
|
[PubMed: 11799477]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/339274]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Decaudain, A., Vantyghem, M.-C., Guerci, B., Hecart, A.-C., Auclair, M., Reznik, Y., Narbonne, H., Ducluzeau, P.-H., Donadille, B., Lebbe, C., Bereziat, V., Capeau, J., Lascols, O., Vigouroux, C.
|
|
<strong>New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.</strong>
|
|
J. Clin. Endocr. Metab. 92: 4835-4844, 2007.
|
|
|
|
|
|
[PubMed: 17711925]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2007-0654]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<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.
|
|
<strong>Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature 423: 293-298, 2003.
|
|
|
|
|
|
[PubMed: 12714972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01629]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E.
|
|
<strong>Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.</strong>
|
|
New Eng. J. Med. 341: 1715-1724, 1999.
|
|
|
|
|
|
[PubMed: 10580070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199912023412302]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Favreau, C., Higuet, D., Courvalin, J.-C., Buendia, B.
|
|
<strong>Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.</strong>
|
|
Molec. Cell. Biol. 24: 1481-1492, 2004.
|
|
|
|
|
|
[PubMed: 14749366]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.24.4.1481-1492.2004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fisher, D. Z., Chaudhary, N., Blobel, G.
|
|
<strong>cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 6450-6454, 1986.
|
|
|
|
|
|
[PubMed: 3462705]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.83.17.6450]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Flier, J. S.
|
|
<strong>Pushing the envelope on lipodystrophy.</strong>
|
|
Nature Genet. 24: 103-104, 2000.
|
|
|
|
|
|
[PubMed: 10655047]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/72734]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Folker, E. S., Ostlund, C., Luxton, G. W. G., Worman, H. J., Gundersen, G. G.
|
|
<strong>Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement.</strong>
|
|
Proc. Nat. Acad. Sci. 108: 131-136, 2011.
|
|
|
|
|
|
[PubMed: 21173262]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1000824108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K.
|
|
<strong>Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.</strong>
|
|
Genes Dev. 20: 486-500, 2006.
|
|
|
|
|
|
[PubMed: 16481476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1364906]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garavelli, L., D'Apice, M. R., Rivieri, F., Bertoli, M., Wischmeijer, A., Gelmini, C., De Nigris, V., Albertini, E., Rosato, S., Virdis, R., Bacchini, E., Dal Zotto, R., Banchini, G., Iughetti, L., Bernasconi, S., Superti-Furga, A., Novelli, G.
|
|
<strong>Mandibuloacral dysplasia type A in childhood.</strong>
|
|
Am. J. Med. Genet. 149A: 2258-2264, 2009.
|
|
|
|
|
|
[PubMed: 19764019]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garg, A., Cogulu, O., Ozkinay, F., Onay, H., Agarwal, A. K.
|
|
<strong>A novel homozygous ala529val LMNA mutation in Turkish patients with mandibuloacral dysplasia.</strong>
|
|
J. Clin. Endocr. Metab. 90: 5259-5264, 2005.
|
|
|
|
|
|
[PubMed: 15998779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-2560]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garg, A., Vinaitheerthan, M., Weatherall, P. T., Bowcock, A. M.
|
|
<strong>Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 59-65, 2001.
|
|
|
|
|
|
[PubMed: 11231979]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.1.7121]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Genschel, J., Bochow, B., Kuepferling, S., Ewert, R., Hetzer, R., Lochs, H., Schmidt, H. H.-J.
|
|
<strong>A R644C mutation within lamin A extends the mutations causing dilated cardiomyopathy.</strong>
|
|
Hum. Genet. 17: 154, 2001.
|
|
|
|
|
|
[PubMed: 11180602]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1098-1004(200102)17:2<154::AID-HUMU11>3.0.CO;2-R]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Genschel, J., Schmidt, H. H.-J.
|
|
<strong>Mutations in the LMNA gene encoding lamin A/C.</strong>
|
|
Hum. Mutat. 16: 451-459, 2000.
|
|
|
|
|
|
[PubMed: 11102973]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1098-1004(200012)16:6<451::AID-HUMU1>3.0.CO;2-9]
|
|
|
|
|
|
</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>
|
|
Hum. Molec. Genet. 14: 2959-2969, 2005.
|
|
|
|
|
|
[PubMed: 16126733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi326]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<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.
|
|
<strong>Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.
|
|
|
|
|
|
[PubMed: 15184648]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0402943101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 3/26/2013.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guilly, M. N., Bensussan, A., Bourge, J. F., Bornens, M., Courvalin, J. C.
|
|
<strong>A human T lymphoblastic cell line lacks lamins A and C.</strong>
|
|
EMBO J. 6: 3795-3799, 1987.
|
|
|
|
|
|
[PubMed: 3501373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1987.tb02715.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gupta, P., Bilinska, Z. T., Sylvius, N., Boudreau, E., Veinot, J. P., Labib, S., Bolongo, P. M., Hamza, A., Jackson, T., Ploski, R., Walski, M., Grzybowski, J., Walczak, E., Religa, G., Fidzianska, A., Tesson, F.
|
|
<strong>Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption.</strong>
|
|
Basic Res. Cardiol. 105: 365-377, 2010.
|
|
|
|
|
|
[PubMed: 20127487]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00395-010-0085-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haque, F., Mazzeo, D., Patel, J. T., Smallwood, D. T., Ellis, J. A., Shanahan, C. M., Shackleton, S.
|
|
<strong>Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.</strong>
|
|
J. Biol. Chem. 285: 3487-3498, 2010.
|
|
|
|
|
|
[PubMed: 19933576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M109.071910]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J., Anderson, C. M.
|
|
<strong>Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.</strong>
|
|
Physiol. Genomics 3: 39-44, 2000.
|
|
|
|
|
|
[PubMed: 11015599]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1152/physiolgenomics.2000.3.1.39]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Huff, M. W., Anderson, C. M.
|
|
<strong>LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.</strong>
|
|
J. Clin. Endocr. Metab. 85: 3089-3093, 2000.
|
|
|
|
|
|
[PubMed: 10999791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.9.6768]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Huff, M. W., Young, T. K.
|
|
<strong>Common genomic variation in LMNA modulates indexes of obesity in Inuit.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2747-2751, 2001.
|
|
|
|
|
|
[PubMed: 11397881]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.6.7550]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A.
|
|
<strong>Drawing the line in progeria syndromes.</strong>
|
|
Lancet 362: 416-417, 2003.
|
|
|
|
|
|
[PubMed: 12927424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(03)14097-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A.
|
|
<strong>LMNA mutation position predicts organ system involvement in laminopathies.</strong>
|
|
Clin. Genet. 68: 31-34, 2005.
|
|
|
|
|
|
[PubMed: 15952983]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00447.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.</strong>
|
|
Am. J. Med. Genet. 155A: 3002-3006, 2011.
|
|
|
|
|
|
[PubMed: 22065502]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.34336]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ho, C. Y., Jaalouk, D. E., Vartiainen, M. K., Lammerding, J.
|
|
<strong>Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.</strong>
|
|
Nature 497: 507-511, 2013.
|
|
|
|
|
|
[PubMed: 23644458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huang, S., Chen, L., Libina, N., Janes, J., Martin, G. M., Campisi, J., Oshima, J.
|
|
<strong>Correction of cellular phenotypes of Hutchinson-Gilford progeria cells by RNA interference.</strong>
|
|
Hum. Genet. 118: 444-450, 2005.
|
|
|
|
|
|
[PubMed: 16208517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-005-0051-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jacob, K. N., Baptista, F., dos Santos, H. G., Oshima, J., Agarwal, A. K., Garg, A.
|
|
<strong>Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous arg133leu lamin A/C mutation.</strong>
|
|
J. Clin. Endocr. Metab. 90: 6699-6706, 2005.
|
|
|
|
|
|
[PubMed: 16174718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-0939]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jimenez-Escrig, A., Gobernado, I., Garcia-Villanueva, M., Sanchez-Herranz, A.
|
|
<strong>Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing.</strong>
|
|
Muscle Nerve 45: 605-610, 2012.
|
|
|
|
|
|
[PubMed: 22431096]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mus.22324]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jung, H.-J., Coffinier, C., Choe, Y., Beigneux, A. P., Davies, B. S. J., Yang, S. H., Barnes, R. H., II, Hong, J., Sun, T., Pleasure, S. J., Young, S. G., Fong, L. G.
|
|
<strong>Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 109: E423-E431, 2012. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 22308344]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1111780109]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jung, H.-J., Tu, Y., Yang, S. H., Tatar, A., Nobumori, C., Wu, D., Young, S. G., Fong, L. G.
|
|
<strong>New Lmna knock-in mice provide a molecular mechanism for the 'segmental aging' in Hutchinson-Gilford progeria syndrome.</strong>
|
|
Hum. Molec. Genet. 23: 1506-1515, 2014.
|
|
|
|
|
|
[PubMed: 24203701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt537]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kandert, S., Luke, Y., Kleinhenz, T., Neumann, S., Lu, W., Jaeger, V. M., Munck, M., Wehnert, M., Muller, C. R., Zhou, Z., Noegel, A. A., Dabauvalle, M.-C., Karakesisoglou, I.
|
|
<strong>Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells.</strong>
|
|
Hum. Molec. Genet. 16: 2944-2959, 2007. Note: Erratum: Hum. Molec. Genet. 17: 468 only, 2008.
|
|
|
|
|
|
[PubMed: 17881656]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm255]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rhys, C., Simonson, L., Dietz, H. C., Michaelis, S.
|
|
<strong>LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.</strong>
|
|
Am. J. Med. Genet. 161A: 1599-1611, 2013.
|
|
|
|
|
|
[PubMed: 23666920]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.35971]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kirschner, J., Brune, T., Wehnert, M., Denecke, J., Wasner, C., Feuer, A., Marquardt, T., Ketelsen, U.-P., Wieacker, P., Bonnemann, C. G., Korinthenberg, R.
|
|
<strong>p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.</strong>
|
|
Ann. Neurol. 57: 148-151, 2005.
|
|
|
|
|
|
[PubMed: 15622532]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20359]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimura, G., Kato, H., Fukushima, Y.
|
|
<strong>Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.</strong>
|
|
Am. J. Med. Genet. 143A: 2598-2603, 2007.
|
|
|
|
|
|
[PubMed: 17935239]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31983]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krohne, G., Benavente, R.
|
|
<strong>The nuclear lamins: a multigene family of proteins in evolution and differentiation.</strong>
|
|
Exp. Cell Res. 162: 1-10, 1986.
|
|
|
|
|
|
[PubMed: 2415378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-4827(86)90421-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lammerding, J., Schulze, P. C., Takahashi, T., Kozlov, S., Sullivan, T., Kamm, R. D., Stewart, C. L., Lee, R. T.
|
|
<strong>Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.</strong>
|
|
J. Clin. Invest. 113: 370-378, 2004.
|
|
|
|
|
|
[PubMed: 14755334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI19670]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lanktree, M., Cao, H., Rabkin, S. W., Hanna, A., Hegele, R. A.
|
|
<strong>Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). (Letter)</strong>
|
|
Clin. Genet. 71: 183-186, 2007.
|
|
|
|
|
|
[PubMed: 17250669]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00740.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lebel, S., Raymond, Y.
|
|
<strong>Lamin A is not synthesized as a larger precursor polypeptide.</strong>
|
|
Biochem. Biophys. Res. Commun. 149: 417-423, 1987.
|
|
|
|
|
|
[PubMed: 3426582]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(87)90383-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Libotte, T., Zaim, H., Abraham, S., Padmakumar, V. C., Schneider, M., Lu, W., Munck, M., Hutchison, C., Wehnert, M., Fahrenkrog, B., Sauder, U., Aebi, U., Noegel, A. A., Karakesisoglou, I.
|
|
<strong>Lamin A/C-dependent localization of nesprin-2, a giant scaffolder at the nuclear envelope.</strong>
|
|
Molec. Biol. Cell 16: 3411-3424, 2005.
|
|
|
|
|
|
[PubMed: 15843432]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1091/mbc.e04-11-1009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, F., Worman, H. J.
|
|
<strong>Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.</strong>
|
|
J. Biol. Chem. 268: 16321-16326, 1993.
|
|
|
|
|
|
[PubMed: 8344919]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature 472: 221-225, 2011.
|
|
|
|
|
|
[PubMed: 21346760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09879]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lloyd, D. J., Trembath, R. C., Shackleton, S.
|
|
<strong>A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.</strong>
|
|
Hum. Molec. Genet. 11: 769-777, 2002.
|
|
|
|
|
|
[PubMed: 11929849]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.7.769]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lombardi, F., Gullotta, F., Columbaro, M., Filareto, A., D'Adamo, M., Vielle, A., Guglielmi, V., Nardone, A. M., Azzolini, V., Grosso, E., Lattanzi, G., D'Apice, M. R., Masala, S., Maraldi, N. M., Sbraccia, P., Novelli, G.
|
|
<strong>Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.</strong>
|
|
J. Clin. Endocr. Metab. 92: 4467-4471, 2007.
|
|
|
|
|
|
[PubMed: 17848409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2007-0116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Machiels, B. M., Zorenc, A. H. G., Endert, J. M., Kuijpers, H. J. H., van Eys, G. J. J. M., Ramaekers, F. C. S., Broers, J. L. V.
|
|
<strong>An alternative splicing product of the lamin A/C gene lacks exon 10.</strong>
|
|
J. Biol. Chem. 271: 9249-9253, 1996.
|
|
|
|
|
|
[PubMed: 8621584]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.16.9249]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Makri, S., Clarke, N. F., Richard, P., Maugenre, S., Demay, L., Bonne, G., Guicheney, P.
|
|
<strong>Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy.</strong>
|
|
Neuromusc. Disord. 19: 26-28, 2009.
|
|
|
|
|
|
[PubMed: 19084400]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2008.09.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Malek, L. A., Labib, S., Mazurkiewicz, L., Saj, M., Ploski, R., Tesson, F., Bilinska, Z. T.
|
|
<strong>A new c.1621 C-G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 56: 83-86, 2011.
|
|
|
|
|
|
[PubMed: 21085127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/jhg.2010.137]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., Michaelis, S.
|
|
<strong>Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 14416-14421, 2005.
|
|
|
|
|
|
[PubMed: 16186497]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0503712102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKeon, F. D., Kirschner, M. W., Caput, D.
|
|
<strong>Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.</strong>
|
|
Nature 319: 463-468, 1986.
|
|
|
|
|
|
[PubMed: 3453101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/319463a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F.
|
|
<strong>Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.</strong>
|
|
Am. J. Med. Genet. 149A: 567-572, 2009.
|
|
|
|
|
|
[PubMed: 19283854]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32627]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mercuri, E., Brown, S. C., Nihoyannopoulos, P., Poulton, J., Kinali, M., Richard, P., Piercy, R. J., Messina, S., Sewry, C., Burke, M. M., McKenna, W., Bonne, G., Muntoni, F.
|
|
<strong>Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.</strong>
|
|
Muscle Nerve 31: 602-609, 2005.
|
|
|
|
|
|
[PubMed: 15770669]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mus.20293]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mercuri, E., Poppe, M., Quinlivan, R., Messina, S., Kinali, M., Demay, L., Bourke, J., Richard, P., Sewry, C., Pike, M., Bonne, G., Muntoni, F., Bushby, K.
|
|
<strong>Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.</strong>
|
|
Arch. Neurol. 61: 690-694, 2004.
|
|
|
|
|
|
[PubMed: 15148145]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.61.5.690]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meune, C., Van Berlo, J. H., Anselme, F., Bonne, G., Pinto, Y. M., Duboc, D.
|
|
<strong>Primary prevention of sudden death in patients with lamin A/C gene mutations. (Letter)</strong>
|
|
New Eng. J. Med. 354: 209-210, 2006.
|
|
|
|
|
|
[PubMed: 16407522]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc052632]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moller, D. V., Pham, T. T., Gustafsson, F., Hedley, P., Ersboll, M. K., Bundgaard, H., Andersen, C. B., Torp-Pedersen, C., Kober, L., Christiansen, M.
|
|
<strong>The role of lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy.</strong>
|
|
Europ. J. Heart Fail. 11: 1031-1035, 2009.
|
|
|
|
|
|
[PubMed: 19875404]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/eurjhf/hfp134]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morel, C. F., Thomas, M. A., Cao, H., O'Neil, C. H., Pickering, J. G., Foulkes, W. D., Hegele, R. A.
|
|
<strong>A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2.</strong>
|
|
J. Clin. Endocr. Metab. 91: 2689-2695, 2006.
|
|
|
|
|
|
[PubMed: 16636128]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-2746]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.</strong>
|
|
Hum. Mutat. 28: 882-889, 2007.
|
|
|
|
|
|
[PubMed: 17469202]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20536]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T., Stewart, C. L.
|
|
<strong>A progeroid syndrome in mice is caused by defects in A-type lamins.</strong>
|
|
Nature 423: 298-301, 2003.
|
|
|
|
|
|
[PubMed: 12748643]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01631]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L.
|
|
<strong>Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.</strong>
|
|
Hum. Molec. Genet. 14: 2167-2180, 2005.
|
|
|
|
|
|
[PubMed: 15972724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi221]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muchir, A., Bonne, G., van der Kooi, A. J., van Meegen, M., Baas, F., Bolhuis, P. A., de Visser, M., Schwartz, K.
|
|
<strong>Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).</strong>
|
|
Hum. Molec. Genet. 9: 1453-1459, 2000.
|
|
|
|
|
|
[PubMed: 10814726]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.9.1453]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muchir, A., Pavlidis,. P., Decostre, V., Herron, A. J., Arimura, T., Bonne, G., Worman, H. J.
|
|
<strong>Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.</strong>
|
|
J. Clin. Invest. 117: 1282-1293, 2007.
|
|
|
|
|
|
[PubMed: 17446932]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI29042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muchir, A., Shan, J., Bonne, G., Lehnart, S. E., Worman, H. J.
|
|
<strong>Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.</strong>
|
|
Hum. Molec. Genet. 18: 241-247, 2009.
|
|
|
|
|
|
[PubMed: 18927124]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn343]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Navarro, C. L., Cadinanos, J., De Sandre-Giovannoli, A., Bernard, R., Courrier, S., Boccaccio, I., Boyer, A., Kleijer, W. J., Wagner, A., Giuliano, F., Beemer, F. A., Freije, J. M., Cau, P., Hennekam, R. C. M., Lopez-Otin, C., Badens, C., Levy, N.
|
|
<strong>Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors.</strong>
|
|
Hum. Molec. Genet. 14: 1503-1513, 2005.
|
|
|
|
|
|
[PubMed: 15843403]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi159]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.</strong>
|
|
Hum. Molec. Genet. 13: 2493-2503, 2004.
|
|
|
|
|
|
[PubMed: 15317753]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh265]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nguyen, D., Leistritz, D. F., Turner, L., MacGregor, D., Ohson, K., Dancey, P., Martin, G. M., Oshima, J.
|
|
<strong>Collagen expression in fibroblasts with a novel LMNA mutation.</strong>
|
|
Biochem. Biophys. Res. Commun. 352: 603-608, 2007.
|
|
|
|
|
|
[PubMed: 17150192]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2006.11.070]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M. R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G.
|
|
<strong>Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.</strong>
|
|
Am. J. Hum. Genet. 71: 426-431, 2002.
|
|
|
|
|
|
[PubMed: 12075506]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/341908]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pan, Y., Garg, A., Agarwal, A. K.
|
|
<strong>Mislocalization of prelamin A Tyr646Phe mutant to the nuclear pore complex in human embryonic kidney 293 cells.</strong>
|
|
Biochem. Biophys. Res. Commun. 355: 78-84, 2007.
|
|
|
|
|
|
[PubMed: 17291448]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2007.01.116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Plasilova, M., Chattopadhyay, C., Pal, P., Schaub, N. A., Buechner, S. A., Mueller, H., Miny, P., Ghosh, A., Heinimann, K.
|
|
<strong>Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.</strong>
|
|
J. Med. Genet. 41: 609-614, 2004.
|
|
|
|
|
|
[PubMed: 15286156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2004.019661]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quijano-Roy, S., Mbieleu, B., Bonnemann, C. G., Jeannet, P.-Y., Colomer, J., Clarke, N. F., Cuisset, J.-M., Roper, H., De Meirleir, L., D'Amico, A., Yaou, R. B., Nascimento, A., and 12 others.
|
|
<strong>De novo LMNA mutations cause a new form of congenital muscular dystrophy.</strong>
|
|
Ann. Neurol. 64: 177-186, 2008.
|
|
|
|
|
|
[PubMed: 18551513]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21417]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raffaele di Barletta, M., Ricci, E., Galluzzi, G., Tonali, P., Mora, M., Morandi, L., Romorini, A., Voit, T., Orstavik, K. H., Merlini, L., Trevisan, C., Biancalana, V., Housmanowa-Petrusewicz, I., Bione, S., Ricotti, R., Schwartz, K., Bonne, G., Toniolo, D.
|
|
<strong>Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 66: 1407-1412, 2000.
|
|
|
|
|
|
[PubMed: 10739764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302869]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rankin, J., Auer-Grumbach, M., Bagg, W., Colclough, K., Duong, N. T., Fenton-May, J., Hattersley, A., Hudson, J., Jardine, P., Josifova, D., Longman, C., McWilliam, R., Owen, K., Walker, M., Wehnert, M., Ellard, S.
|
|
<strong>Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.</strong>
|
|
Am. J. Med. Genet. 146A: 1530-1542, 2008.
|
|
|
|
|
|
[PubMed: 18478590]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32331]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reddel, C. J., Weiss, A. S.
|
|
<strong>Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.</strong>
|
|
J. Med. Genet. 41: 715-717, 2004.
|
|
|
|
|
|
[PubMed: 15342704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2004.019323]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Renou, L., Stora, S., Yaou, R. B., Volk, M., Sinkovec, M., Demay, L., Richard, P., Peterlin, B., Bonne, G.
|
|
<strong>Heart-hand syndrome of Slovenian type: a new kind of laminopathy. (Letter)</strong>
|
|
J. Med. Genet. 45: 666-671, 2008.
|
|
|
|
|
|
[PubMed: 18611980]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.060020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rodriguez, S., Coppede, F., Sagelius, H., Eriksson, M.
|
|
<strong>Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging.</strong>
|
|
Europ. J. Hum. Genet. 17: 928-937, 2009.
|
|
|
|
|
|
[PubMed: 19172989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2008.270]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Botzenhart, E., Eggermann, T., Senderek, J., Schoser, B. G. H., Schroder, R., Wehnert, M., Wirth, B., Zerres, K.
|
|
<strong>Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.</strong>
|
|
Neurogenetics 8: 137-142, 2007.
|
|
|
|
|
|
[PubMed: 17136397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-006-0070-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.</strong>
|
|
Nature Med. 11: 440-445, 2005.
|
|
|
|
|
|
[PubMed: 15750600]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm1204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Lamin A-dependent nuclear defects in human aging.</strong>
|
|
Science 312: 1059-1063, 2006.
|
|
|
|
|
|
[PubMed: 16645051]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1127168]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scaffidi, P., Misteli, T.
|
|
<strong>Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.</strong>
|
|
Nature Cell Biol. 10: 452-459, 2008.
|
|
|
|
|
|
[PubMed: 18311132]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ncb1708]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scharner, J., Brown, C. A., Bower, M., Iannaccone, S. T., Khatri, I. A., Escolar, D., Gordon, E., Felice, K., Crowe, C. A., Grosmann, C., Meriggioli, M. N., Asamoah, A., Gordon, O., Gnocchi, V. F., Ellis, J. A., Mendell, J. R., Zammit, P. S.
|
|
<strong>Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.</strong>
|
|
Hum. Mutat. 32: 152-167, 2011.
|
|
|
|
|
|
[PubMed: 20848652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.21361]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schmidt, H. H.-J., Genschel, J., Baier, P., Schmidt, M., Ockenga, J., Tietge, U. J. F., Propsting, M., Buttner, C., Manns, M. P., Lochs, H., Brabant, G.
|
|
<strong>Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2289-2295, 2001.
|
|
|
|
|
|
[PubMed: 11344241]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.5.7500]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schreiber, K. H., Kennedy, B. K.
|
|
<strong>When lamins go bad: nuclear structure and disease.</strong>
|
|
Cell 152: 1365-1375, 2013.
|
|
|
|
|
|
[PubMed: 23498943]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2013.02.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M.
|
|
<strong>Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.</strong>
|
|
J. Med. Genet. 40: 560-567, 2003.
|
|
|
|
|
|
[PubMed: 12920062]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.40.8.560]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shackleton, S., Lloyd, D. J., Jackson, S. N. J., Evans, R., Niermeijer, M. F., Singh, B. M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P. N., Gregory, S., O'Rahilly, S., Trembath, R. C.
|
|
<strong>LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.</strong>
|
|
Nature Genet. 24: 153-156, 2000.
|
|
|
|
|
|
[PubMed: 10655060]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/72807]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shen, J. J., Brown, C. A., Lupski, J. R., Potocki, L.
|
|
<strong>Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C.</strong>
|
|
J. Med. Genet. 40: 854-857, 2003.
|
|
|
|
|
|
[PubMed: 14627682]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.40.11.854]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shumaker, D. K., Dechat, T., Kohlmaier, A., Adam, S. A., Bozovsky, M. R., Erdos, M. R., Eriksson, M., Goldman, A. E., Khuon, S., Collins, F. S., Jenuwein, T., Goldman, R. D.
|
|
<strong>Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 8703-8708, 2006.
|
|
|
|
|
|
[PubMed: 16738054]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0602569103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simha, V., Agarwal, A. K., Oral, E. A., Fryns, J.-P., Garg, A.
|
|
<strong>Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2821-2824, 2003.
|
|
|
|
|
|
[PubMed: 12788894]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021575]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simon, D. N., Domaradzki, T., Hofmann, W. A., Wilson, K. L.
|
|
<strong>Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.</strong>
|
|
Molec. Biol. Cell 24: 342-350, 2013.
|
|
|
|
|
|
[PubMed: 23243001]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1091/mbc.E12-07-0527]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sinensky, M., Fantle, K., Trujillo, M., McLain, T., Kupfer, A., Dalton, M.
|
|
<strong>The processing pathway of prelamin A.</strong>
|
|
J. Cell Sci. 107: 61-67, 1994.
|
|
|
|
|
|
[PubMed: 8175923]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1242/jcs.107.1.61]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sinkovec, M., Petrovic, D., Volk, M., Peterlin, B.
|
|
<strong>Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly: a new type of heart-hand syndrome?</strong>
|
|
Clin. Genet. 68: 155-160, 2005.
|
|
|
|
|
|
[PubMed: 15996213]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00476.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Speckman, R. A., Garg, A., Du, F., Bennett, L., Veile, R., Arioglu, E., Taylor, S. I., Lovett, M., Bowcock, A. M.
|
|
<strong>Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.</strong>
|
|
Am. J. Hum. Genet. 66: 1192-1198, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 775 only, 2000.
|
|
|
|
|
|
[PubMed: 10739751]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302836]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Straub, V., Murphy, A., Udd, B.
|
|
<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
|
|
Neuromusc. Disord. 28: 702-710, 2018.
|
|
|
|
|
|
[PubMed: 30055862]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2018.05.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group.
|
|
<strong>Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.</strong>
|
|
J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003.
|
|
|
|
|
|
[PubMed: 12628721]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0735-1097(02)02954-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomasson, R., Vignier, N., Peccate, C., Mougenot, N., Noirez, P., Muchir, A.
|
|
<strong>Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.</strong>
|
|
Hum. Molec. Genet. 28: 2237-2244, 2019.
|
|
|
|
|
|
[PubMed: 31220270]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddz056]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Toth, J. I., Yang, S. H., Qiao, X., Beigneux, A. P., Gelb, M. H., Moulson, C. L., Miner, J. H., Young, S. G., Fong, L. G.
|
|
<strong>Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 12873-12878, 2005.
|
|
|
|
|
|
[PubMed: 16129834]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0505767102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vadrot, N., Duband-Goulet, I., Cabet, E., Attanda, W., Barateau, A., Vicart, P., Gerbal, F., Briand, N., Vigouroux, C., Oldenburg, A. R., Lund, E. G., Collas, P., Buendia, B.
|
|
<strong>The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.</strong>
|
|
Hum. Molec. Genet. 24: 2096-2109, 2015.
|
|
|
|
|
|
[PubMed: 25524705]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu728]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Berlo, J. H., Voncken, J. W., Kubben, N., Broers, J. L. V., Duisters, R., van Leeuwen, R. E. W., Crijns, H. J. G. M., Ramaekers, F. C. S., Hutchison, C. J., Pinto, Y. M.
|
|
<strong>A-type lamins are essential for TGF-beta-1 induced PP2A to dephosphorylate transcription factors.</strong>
|
|
Hum. Molec. Genet. 14: 2839-2849, 2005.
|
|
|
|
|
|
[PubMed: 16115815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi316]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., Bonne, G., Eymard, B., Duboc, D., Talim, B., Van der Valk, M., Reiss, P., Richard, P., Demay, L., Merlini, L., Schwartz, K., Busch, H. F. M., de Visser, M.
|
|
<strong>Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.</strong>
|
|
Neurology 59: 620-623, 2002.
|
|
|
|
|
|
[PubMed: 12196663]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.59.4.620]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., Ledderhof, T. M., de Voogt, W. G., Res, J. C. J., Bouwsma, G., Troost, D., Busch, H. F. M., Becker, A. E., de Visser, M.
|
|
<strong>A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement.</strong>
|
|
Ann. Neurol. 39: 636-642, 1996.
|
|
|
|
|
|
[PubMed: 8619549]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410390513]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Kooi, A. J., van Meegen, M., Ledderhof, T. M., McNally, E. M., de Visser, M., Bolhuis, P. A.
|
|
<strong>Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21.</strong>
|
|
Am. J. Hum. Genet. 60: 891-895, 1997.
|
|
|
|
|
|
[PubMed: 9106535]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van Engelen, B. G. M., Muchir, A., Hutchison, C. J., van der Kooi, A. J., Bonne, G., Lammens, M.
|
|
<strong>The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene.</strong>
|
|
Neurology 64: 374-376, 2005.
|
|
|
|
|
|
[PubMed: 15668447]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.WNL.0000149763.15180.00]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Agarwal, A. K., Debeer, P., Fryns, J.-P., Garg, A.
|
|
<strong>A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.</strong>
|
|
J. Clin. Endocr. Metab. 91: 517-521, 2006.
|
|
|
|
|
|
[PubMed: 16278265]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-1297]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vantyghem, M. C., Pigny, P., Maurage, C. A., Rouaix-Emery, N., Stojkovic, T., Cuisset, J. M., Millaire, A., Lascols, O., Vermersch, P., Wemeau, J. L., Capeau, J., Vigouroux, C.
|
|
<strong>Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5337-5346, 2004.
|
|
|
|
|
|
[PubMed: 15531479]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-031658]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
<strong>Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 3250-3255, 2006.
|
|
|
|
|
|
[PubMed: 16492728]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0600012103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vigouroux, C., Auclair, M., Dubosclard, E., Pouchelet, M., Capeau, J., Courvalin, J.-C., Buendia, B.
|
|
<strong>Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.</strong>
|
|
J. Cell Sci. 114: 4459-4468, 2001.
|
|
|
|
|
|
[PubMed: 11792811]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1242/jcs.114.24.4459]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vigouroux, C., Caux, F. Capeau, J., Christin-Maitre, S., Cohen, A.
|
|
<strong>LMNA mutations in atypical Werner's syndrome. (Letter)</strong>
|
|
Lancet 362: 1585 only, 2003.
|
|
|
|
|
|
[PubMed: 14615128]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(03)14760-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, Y., Shilagardi, K., Hsu, T., Odinammadu, K. O., Maruyama, T., Wu, W., Lin, C. S., Damoci, C. B., Spear, E. D., Shin, J. Y., Hsu, W., Michaelis, S., Worman, H. J.
|
|
<strong>Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 119: e2118695119, 2022.
|
|
|
|
|
|
[PubMed: 35197292]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.2118695119]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weber, K., Plessmann, U., Traub, P.
|
|
<strong>Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina.</strong>
|
|
FEBS Lett. 257: 411-414, 1989.
|
|
|
|
|
|
[PubMed: 2583287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(89)81584-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wiltshire, K. M., Hegele, R. A., Innes, A. M., Brownell, A. K. W.
|
|
<strong>Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.</strong>
|
|
Neuromusc. Disord. 23: 265-268, 2013.
|
|
|
|
|
|
[PubMed: 23313286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2012.11.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Worman, H. J., Bonne, G.
|
|
<strong>'Laminopathies': a wide spectrum of human diseases.</strong>
|
|
Exp. Cell Res. 313: 2121-2133, 2007.
|
|
|
|
|
|
[PubMed: 17467691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.yexcr.2007.03.028]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wuyts, W., Biervliet, M., Reyniers, E., D'Apice, M. R., Novelli, G., Storm, K.
|
|
<strong>Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.</strong>
|
|
Am. J. Med. Genet. 135A: 66-68, 2005.
|
|
|
|
|
|
[PubMed: 15793835]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30663]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B.
|
|
<strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong>
|
|
Genomics 32: 474-478, 1996.
|
|
|
|
|
|
[PubMed: 8838815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0146]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, S. H., Andres, D. A., Spielmann, H. P., Young, S. G., Fong, L. G.
|
|
<strong>Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated.</strong>
|
|
J. Clin. Invest. 118: 3291-3300, 2008.
|
|
|
|
|
|
[PubMed: 18769635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI35876]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, S. H., Bergo, M. O., Toth, J. I., Qiao, X., Hu, Y., Sandoval, S., Meta, M., Bendale, P., Gelb, M. H., Young, S. G., Fong, L. G.
|
|
<strong>Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 10291-10296, 2005.
|
|
|
|
|
|
[PubMed: 16014412]
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|
|
|
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[Full Text: https://doi.org/10.1073/pnas.0504641102]
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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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<strong>A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.</strong>
|
|
J. Clin. Invest. 116: 2115-2121, 2006.
|
|
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[PubMed: 16862216]
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|
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[Full Text: https://doi.org/10.1172/JCI28968]
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Zaragoza, M. V., Hakim, S. A., Hoang, V., Elliott, A. M.
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<strong>Heart-hand syndrome IV: a second family with LMNA-related cardiomyopathy and brachydactyly. (Letter)</strong>
|
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Clin. Genet. 91: 499-500, 2017.
|
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[PubMed: 27723096]
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[Full Text: https://doi.org/10.1111/cge.12870]
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Zirn, B., Kress, W., Grimm, T., Berthold, L. D., Neubauer, B., Kuchelmeister, K., Muller, U., Hahn, A.
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<strong>Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.</strong>
|
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Am. J. Med. Genet. 146A: 1049-1054, 2008.
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[PubMed: 18348272]
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[Full Text: https://doi.org/10.1002/ajmg.a.32259]
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Bao Lige - updated : 12/01/2022<br>Bao Lige - updated : 02/08/2022<br>Carol A. Bocchini - updated : 11/19/2018<br>Patricia A. Hartz - updated : 10/28/2016<br>Cassandra L. Kniffin - updated : 10/27/2015<br>Cassandra L. Kniffin - updated : 9/4/2015<br>Cassandra L. Kniffin - updated : 8/13/2015<br>Patricia A. Hartz - updated : 11/25/2014<br>Patricia A. Hartz - updated : 8/6/2014<br>Marla J. F. O'Neill - updated : 4/30/2014<br>Carol A. Bocchini - updated : 2/18/2014<br>George E. Tiller - updated : 9/10/2013<br>George E. Tiller - updated : 8/23/2013<br>Ada Hamosh - updated : 7/11/2013<br>Patricia A. Hartz - updated : 6/10/2013<br>Matthew B. Gross - updated : 3/26/2013<br>Cassandra L. Kniffin - updated : 10/3/2012<br>Ada Hamosh - updated : 6/7/2011<br>Cassandra L. Kniffin - updated : 2/14/2011<br>Marla J. F. O'Neill - updated : 10/19/2010<br>Cassandra L. Kniffin - updated : 10/13/2010<br>Paul J. Converse - updated : 9/20/2010<br>Patricia A. Hartz - updated : 8/10/2010<br>Patricia A. Hartz - updated : 7/27/2010<br>Cassandra L. Kniffin - updated : 4/7/2010<br>Nara Sobreira - updated : 1/8/2010<br>Cassandra L. Kniffin - updated : 1/5/2010<br>Cassandra L. Kniffin - updated : 11/2/2009<br>George E. Tiller - updated : 8/3/2009<br>Cassandra L. Kniffin - updated : 7/9/2009<br>Patricia A. Hartz - updated : 6/30/2009<br>George E. Tiller - updated : 5/13/2009<br>George E. Tiller - updated : 4/22/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 3/5/2009<br>Marla J. F. O'Neill - updated : 2/19/2009<br>George E. Tiller - updated : 11/19/2008<br>Paul J. Converse - updated : 10/27/2008<br>John A. Phillips, III - updated : 9/23/2008<br>John A. Phillips, III - updated : 9/23/2008<br>George E. Tiller - updated : 6/5/2008<br>Cassandra L. Kniffin - updated : 1/30/2008<br>Marla J. F. O'Neill - updated : 11/21/2007<br>Cassandra L. Kniffin - updated : 11/7/2007<br>George E. Tiller - updated : 10/31/2007<br>Cassandra L. Kniffin - updated : 10/16/2007<br>John A. Phillips, III - updated : 7/17/2007<br>George E. Tiller - updated : 6/13/2007<br>Cassandra L. Kniffin - updated : 5/2/2007<br>John A. Phillips, III - updated : 4/9/2007<br>John A. Phillips, III - updated : 3/22/2007<br>Marla J. F. O'Neill - updated : 3/8/2007<br>Ada Hamosh - updated : 8/1/2006<br>Cassandra L. Kniffin - updated : 6/26/2006<br>Patricia A. Hartz - updated : 3/28/2006<br>Marla J. F. O'Neill - updated : 3/22/2006<br>Marla J. F. O'Neill - updated : 2/15/2006<br>Victor A. McKusick - updated : 2/1/2006<br>Marla J. F. O'Neill - updated : 7/5/2005<br>Marla J. F. O'Neill - updated : 6/1/2005<br>George E. Tiller - updated : 5/19/2005<br>Victor A. McKusick - updated : 5/11/2005<br>John A. Phillips, III - updated : 4/13/2005<br>Victor A. McKusick - updated : 3/15/2005<br>Victor A. McKusick - updated : 2/22/2005<br>Victor A. McKusick - updated : 2/17/2005<br>Marla J. F. O'Neill - updated : 11/3/2004<br>Patricia A. Hartz - updated : 10/27/2004<br>Victor A. McKusick - updated : 10/12/2004<br>Cassandra L. Kniffin - reorganized : 5/3/2004<br>Cassandra L. Kniffin - updated : 4/15/2004<br>Victor A. McKusick - updated : 2/25/2004<br>Patricia A. Hartz - updated : 2/17/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 1/20/2004<br>Cassandra L. Kniffin - updated : 1/6/2004<br>Victor A. McKusick - updated : 10/22/2003<br>Victor A. McKusick - updated : 10/1/2003<br>John A. Phillips, III - updated : 8/25/2003<br>John A. Phillips, III - updated : 8/25/2003<br>Victor A. McKusick - updated : 6/11/2003<br>Ada Hamosh - updated : 5/28/2003<br>Ada Hamosh - updated : 4/29/2003<br>Ada Hamosh - updated : 4/23/2003<br>Ada Hamosh - updated : 4/16/2003<br>Cassandra L. Kniffin - updated : 12/16/2002<br>George E. Tiller - updated : 10/28/2002<br>Victor A. McKusick - updated : 8/16/2002<br>Victor A. McKusick - updated : 3/21/2002<br>John A. Phillips, III - updated : 11/6/2001<br>John A. Phillips, III - updated : 10/4/2001<br>John A. Phillips, III - updated : 7/16/2001<br>John A. Phillips, III - updated : 3/16/2001<br>Victor A. McKusick - updated : 1/2/2001<br>George E. Tiller - updated : 8/16/2000<br>Victor A. McKusick - updated : 7/20/2000<br>Victor A. McKusick - updated : 4/13/2000<br>Paul Brennan - updated : 4/10/2000<br>Victor A. McKusick - updated : 1/28/2000<br>Victor A. McKusick - updated : 12/14/1999<br>Victor A. McKusick - updated : 12/3/1999<br>Victor A. McKusick - updated : 2/23/1999<br>Alan F. Scott - updated : 4/22/1996
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Victor A. McKusick : 1/5/1988
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carol : 01/11/2023<br>mgross : 12/01/2022<br>alopez : 11/17/2022<br>carol : 03/14/2022<br>carol : 03/11/2022<br>mgross : 02/08/2022<br>alopez : 02/12/2020<br>carol : 11/19/2018<br>carol : 10/05/2018<br>carol : 09/26/2018<br>carol : 09/25/2018<br>carol : 10/29/2016<br>alopez : 10/28/2016<br>alopez : 08/04/2016<br>carol : 10/29/2015<br>ckniffin : 10/27/2015<br>carol : 9/9/2015<br>ckniffin : 9/4/2015<br>carol : 8/18/2015<br>alopez : 8/14/2015<br>mcolton : 8/13/2015<br>ckniffin : 8/13/2015<br>mgross : 11/26/2014<br>mcolton : 11/25/2014<br>mgross : 10/14/2014<br>mgross : 10/14/2014<br>mcolton : 8/6/2014<br>carol : 6/15/2014<br>carol : 5/1/2014<br>mcolton : 4/30/2014<br>carol : 2/18/2014<br>carol : 9/18/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 9/10/2013<br>tpirozzi : 8/23/2013<br>alopez : 7/11/2013<br>mgross : 6/10/2013<br>mgross : 6/10/2013<br>alopez : 6/10/2013<br>mgross : 3/26/2013<br>carol : 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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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