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Entry
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- *300163 - FOUR-AND-A-HALF LIM DOMAINS 1; FHL1
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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">*300163</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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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 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">
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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/300163">Table View</a>
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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 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=ENSG00000022267;t=ENST00000370683" 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=2273" 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=300163" 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=ENSG00000022267;t=ENST00000370683" 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_001159699,NM_001159700,NM_001159701,NM_001159702,NM_001159703,NM_001159704,NM_001167819,NM_001330659,NM_001369326,NM_001369327,NM_001369328,NM_001369329,NM_001369330,NM_001369331,NM_001449,NR_027621,XM_006724743,XM_006724746,XM_024452354,XM_047441925,XM_047441926,XM_047441927" 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_001159699" 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=300163" 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=02157&isoform_id=02157_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/FHL1" 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/1381814,2078480,2853224,3851650,3859849,4512028,6942193,15012184,21361122,48146065,56789520,59800384,62898159,119608882,119608883,119608884,119608885,158259845,193784136,193787195,221041652,221042684,221042686,221042718,221043414,221043704,221045120,228480205,228480207,228480209,228480211,228480213,228480221,268607694,578838645,578838651,1060856488,1370516008,1606715863,1606838586,1606838591,1606838600,1606838608,1606838617,2217391388,2217391391,2217391393,2462628716,2462628718,2462628720,2462628722,2462628724,2462628726" 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/Q13642" 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=2273" 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=ENSG00000022267;t=ENST00000370683" 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=FHL1" 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=FHL1" 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+2273" 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/FHL1" 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:2273" 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/2273" 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=chrX&hgg_gene=ENST00000394155.8&hgg_start=136146702&hgg_end=136211359&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300163[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=300163[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/FHL1/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/ENSG00000022267" 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=FHL1" 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=FHL1" 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=FHL1" 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="http://www.LOVD.nl/FHL1" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FHL1&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/PA28141" 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:3702" 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://www.mousephenotype.org/data/genes/MGI:1298387" 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/FHL1#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:1298387" 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/2273/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://www.orthodb.org/?ncbi=2273" 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://zfin.org/ZDB-GENE-031219-1" 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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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:2273" 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=FHL1&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> 773729007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
300163
|
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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>
|
|
<span class="mim-font">
|
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FOUR-AND-A-HALF LIM DOMAINS 1; FHL1
|
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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 />
|
|
</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
SLIM1<br />
|
|
FHL1A<br />
|
|
KYOT, MOUSE, HOMOLOG OF
|
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</span>
|
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</h4>
|
|
</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>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
FHL1B, INCLUDED
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<span class="h4 mim-font">
|
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|
|
SLIMMER, INCLUDED<br />
|
|
FHL1C, INCLUDED
|
|
</span>
|
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</div>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FHL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FHL1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/717?start=-3&limit=10&highlight=717">Xq26.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:136146702-136211359&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'})">X:136,146,702-136,211,359</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
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|
|
</span>
|
|
</p>
|
|
</div>
|
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|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300280,300696,300696,300717,300718,300695" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/717?start=-3&limit=10&highlight=717">
|
|
Xq26.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Uruguay faciocardiomusculoskeletal syndrome
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300280"> 300280 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</td>
|
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</tr>
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Emery-Dreifuss muscular dystrophy 6, X-linked
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<a href="/entry/300696"> 300696 </a>
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<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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Myopathy, X-linked, with postural muscle atrophy
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Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset
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<abbr class="mim-tip-hint" title="X-linked dominant">XLD</abbr>
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Reducing body myopathy, X-linked 1b, with late childhood or adult onset
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Scapuloperoneal myopathy, X-linked dominant
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<a href="/entry/300695"> 300695 </a>
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<abbr class="mim-tip-hint" title="X-linked dominant">XLD</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/300163" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/300163" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>LIM proteins, named for 'LIN11, ISL1, and MEC3,' are defined by the possession of a highly conserved double zinc finger motif called the LIM domain.</p>
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<p><a href="#12" class="mim-tip-reference" title="Morgan, M. J., Madgwick, A. J., Charleston, B., Pell, J. M., Loughna, P. T. <strong>The developmental regulation of a novel muscle LIM-protein.</strong> Biochem. Biophys. Res. Commun. 212: 840-846, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626119</a>] [<a href="https://doi.org/10.1006/bbrc.1995.2045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626119">Morgan et al. (1995)</a> identified a partial human SLIM1 cDNA. They found that SLIM1 is a developmentally regulated protein that is expressed in human skeletal muscle but not in a variety of other tissues. By searching sequence databases with the partial SLIM1 cDNA isolated by <a href="#12" class="mim-tip-reference" title="Morgan, M. J., Madgwick, A. J., Charleston, B., Pell, J. M., Loughna, P. T. <strong>The developmental regulation of a novel muscle LIM-protein.</strong> Biochem. Biophys. Res. Commun. 212: 840-846, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626119</a>] [<a href="https://doi.org/10.1006/bbrc.1995.2045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626119">Morgan et al. (1995)</a>, <a href="#11" class="mim-tip-reference" title="Morgan, M. J., Madgwick, A. J. A. <strong>Slim defines a novel family of LIM-proteins expressed in skeletal muscle.</strong> Biochem. Biophys. Res. Commun. 225: 632-638, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8753811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8753811</a>] [<a href="https://doi.org/10.1006/bbrc.1996.1222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8753811">Morgan and Madgwick (1996)</a> identified human cDNAs encoding the complete SLIM1 amino acid sequence. The predicted 280-amino acid protein contains 4 LIM domains and a novel single zinc finger domain in the N-terminal region. By Northern blot analysis, SLIM1 is expressed as a 2.3-kb mRNA in human masseter muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8753811+7626119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Northern blot analysis, <a href="#4" class="mim-tip-reference" title="Greene, W. K., Baker, E., Rabbitts, T. H., Kees, U. R. <strong>Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.</strong> Gene 232: 203-207, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352231</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00125-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352231">Greene et al. (1999)</a> found a 2.5-kb transcript strongly expressed in skeletal muscle and to a lesser extent in heart. Significantly lower expression was observed in prostate, testis, ovary, small and large intestine, placenta, and lung, while barely detectable expression was seen in spleen, thymus, and pancreas. No expression was detected in leukocytes, brain, liver, and kidney. A second transcript of about 1.3-kb was found at low levels in testis, heart, and skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 sequence derived from the 5-prime end of inositol polyphosphate 5-phosphatase (INPP5A; <a href="/entry/600106">600106</a>) as a probe, <a href="#1" class="mim-tip-reference" title="Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., Mitchell, C. A. <strong>Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1: localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.</strong> J. Biol. Chem. 274: 27083-27091, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480922</a>] [<a href="https://doi.org/10.1074/jbc.274.38.27083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10480922">Brown et al. (1999)</a> cloned FHL1, which they called SLIM1, from a bone marrow cDNA library. Sequence analysis revealed that each LIM domain is separated by 8 intervening amino acids. SLIM1 shares 47% sequence identity with SLIM3 (FHL2; <a href="/entry/602633">602633</a>) and 45% identity with SLIM2 (FHL3; <a href="/entry/602790">602790</a>). SLIM1 shares no homology with INPP5A except for a 16-nucleotide stretch contained within the probe used to screen the library. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., Mitchell, C. A. <strong>Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1: localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.</strong> J. Biol. Chem. 274: 27083-27091, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480922</a>] [<a href="https://doi.org/10.1074/jbc.274.38.27083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10480922">Brown et al. (1999)</a> also cloned an alternatively spliced isoform, which they called SLIMMER (FHL1B), that differs from SLIM1 with a 200-bp insertion that causes a frameshift. The deduced protein contains 323 amino acids and has a calculated molecular mass of 34 kD. It contains an N-terminal zinc finger followed by 3 LIM domains identical to SLIM1, and a novel 93-amino acid C terminus that contains 3 bipartite nuclear localization signals (NLS) followed by a leucine-rich nuclear export sequence (NES). Northern blot analysis revealed a 2.4-kb SLIMMER transcript expressed at high levels in skeletal muscle and at lower levels in heart, colon, prostate, and small intestine. A 4.4-kb transcript was also observed in skeletal muscle and colon. Western blot analysis of skeletal muscle using isoform-specific antibodies revealed endogenous expression of both a 34-kD SLIMMER protein and a 32-kD SLIM1 protein. Fluorescence-tagged SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in transfected COS-7 cells, while fluorescence-tagged SLIMMER was predominantly nuclear. Truncation mutants revealed that the first NLS mediated SLIMMER nuclear localization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., Mitchell, C. A. <strong>Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1: localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.</strong> J. Biol. Chem. 274: 27083-27091, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480922</a>] [<a href="https://doi.org/10.1074/jbc.274.38.27083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10480922">Brown et al. (1999)</a> found that endogenous Slim1 showed diffuse cytoplasmic staining and low nuclear staining in mouse myoblasts. Following differentiation into multinucleated myotubes, Slim1 staining became exclusively cytoplasmic. SLIMMER showed prominent nuclear staining of myoblasts and exclusively cytoplasmic staining of myotubes. The leucine-rich NES was required for the export of Slimmer from the nucleus of mouse myoblasts to the cytoplasm of differentiated myotubes. By Northern blot analysis of mouse tissues, <a href="#3" class="mim-tip-reference" title="Fimia, G. M., De Cesare, D., Sassone-Corsi, P. <strong>A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM.</strong> Molec. Cell. Biol. 20: 8613-8622, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11046156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11046156</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11046156[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.20.22.8613-8622.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11046156">Fimia et al. (2000)</a> determined that Fhl1 was the only Fhl transcript tested that was expressed in a wide range of tissues. High levels were present in heart, skeletal muscle, ovary, kidney, lung, and brain, and much lower levels were found in spleen, liver, adrenal gland, testis, and pituitary. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11046156+10480922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ng, E. K. O., Lee, S. M. Y., Li, H.-Y., Ngai, S.-M., Tsui, S. K. W., Waye, M. M. Y., Lee, C.-Y., Fung, K.-P. <strong>Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of human LIM-only protein (FHL1).</strong> J. Cell. Biochem. 82: 1-10, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11400158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11400158</a>] [<a href="https://doi.org/10.1002/jcb.1110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11400158">Ng et al. (2001)</a> identified a third alternatively spliced isoform of the FHL1 gene, which they designated FHL1C. The deduced 195-residue FHL1C isoform contains a single zinc finger and 2 tandem repeats of LIM domains at the N terminus, followed by a putative RBPJ-binding region at the C terminus. FHL1C lacks exon 4, resulting in a frameshift in the 3-prime coding region and absence of a putative nuclear export sequence coded by exon 4b. Northern blot and RT-PCR analysis showed that FHL1C was specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1A. Low levels of FHL1C expression were observed in aorta, left atrium, and left and right ventricles. Western blot analysis detected a 20-kD corresponding to FHL1C in human skeletal muscle and heart. Unlike FHL1B, which is located primarily in the nucleus, FHL1C was localized both in the nucleus and cytoplasm of mammalian cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11400158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Greene, W. K., Baker, E., Rabbitts, T. H., Kees, U. R. <strong>Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.</strong> Gene 232: 203-207, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352231</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00125-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352231">Greene et al. (1999)</a> determined that the FHL1 gene contains at least 5 exons and spans over 3.6 kb. All 4 introns disrupt the coding region at regular intervals near the start of each complete LIM motif, implying that exon duplication may be responsible for the tandem LIM domain repeats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 FHL1A isoform contains exons 1 through 5, FHL1B contains exons 1, 2, 3, 4, 4b, and 5, and FHL1C contains 1, 2, 3, and 5 (<a href="#13" class="mim-tip-reference" title="Ng, E. K. O., Lee, S. M. Y., Li, H.-Y., Ngai, S.-M., Tsui, S. K. W., Waye, M. M. Y., Lee, C.-Y., Fung, K.-P. <strong>Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of human LIM-only protein (FHL1).</strong> J. Cell. Biochem. 82: 1-10, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11400158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11400158</a>] [<a href="https://doi.org/10.1002/jcb.1110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11400158">Ng et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11400158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>By somatic cell hybrid mapping, FISH, and radiation hybrid mapping, <a href="#9" class="mim-tip-reference" title="Lee, S. M. Y., Tsui, S. K. W., Chan, K. K., Garcia-Barcelo, M., Waye, M. M. Y., Fung, K. P., Liew, C. C., Lee, C. Y. <strong>Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1).</strong> Gene 216: 163-170, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714789</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00302-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9714789">Lee et al. (1998)</a> mapped the FHL1 gene to chromosome Xq27.2. By FISH, <a href="#4" class="mim-tip-reference" title="Greene, W. K., Baker, E., Rabbitts, T. H., Kees, U. R. <strong>Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.</strong> Gene 232: 203-207, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352231</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00125-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352231">Greene et al. (1999)</a> mapped the FHL1 gene to Xq26. In connection with myopathy caused by mutations in the FHL1 gene, <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> indirectly mapped the FHL1 gene to Xq26.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18179888+10352231+9714789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#10" class="mim-tip-reference" title="Meertens, L., Hafirassou, M. L., Couderc, T., Bonnet-Madin, L., Kril, V., Kummerer, B. M., Labeau, A., Brugier, A., Simon-Loriere, E., Burlaud-Gaillard, J., Doyen, C., Pezzi, L., and 14 others. <strong>FHL1 is a major host factor for chikungunya virus infection.</strong> Nature 574: 259-263, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31554973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31554973</a>] [<a href="https://doi.org/10.1038/s41586-019-1578-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31554973">Meertens et al. (2019)</a> identified FHL1 as a host factor that is required for chikungunya virus permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression resulted in the inhibition of infection by several chikungunya strains and o'nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 in cells that do not normally express it promoted chikungunya infection. <a href="#10" class="mim-tip-reference" title="Meertens, L., Hafirassou, M. L., Couderc, T., Bonnet-Madin, L., Kril, V., Kummerer, B. M., Labeau, A., Brugier, A., Simon-Loriere, E., Burlaud-Gaillard, J., Doyen, C., Pezzi, L., and 14 others. <strong>FHL1 is a major host factor for chikungunya virus infection.</strong> Nature 574: 259-263, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31554973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31554973</a>] [<a href="https://doi.org/10.1038/s41586-019-1578-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31554973">Meertens et al. (2019)</a> found that FHL1 interacts directly with the hypervariable domain of the nsP3 protein of chikungunya and is essential for the replication of viral RNA. FHL1 is highly expressed in chikungunya target cells and is particularly abundant in muscles. Dermal fibroblasts and muscle cells derived from patients with Emery-Dreifuss muscular dystrophy (see <a href="/entry/300696">300696</a>) that lacked functional FHL1 were resistant to chikungunya infection. Furthermore, chikungunya infection was undetectable in Fhl1-knockout mice. <a href="#10" class="mim-tip-reference" title="Meertens, L., Hafirassou, M. L., Couderc, T., Bonnet-Madin, L., Kril, V., Kummerer, B. M., Labeau, A., Brugier, A., Simon-Loriere, E., Burlaud-Gaillard, J., Doyen, C., Pezzi, L., and 14 others. <strong>FHL1 is a major host factor for chikungunya virus infection.</strong> Nature 574: 259-263, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31554973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31554973</a>] [<a href="https://doi.org/10.1038/s41586-019-1578-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31554973">Meertens et al. (2019)</a> concluded that their study showed that FHL1 is a key factor expressed by the host that enables chikungunya virus infection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31554973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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><strong><em>Scapuloperoneal Myopathy, X-linked</em></strong></p><p>
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Scapuloperoneal syndrome encompasses heterogeneous neuromuscular disorders characterized by weakness in the shoulder girdle and peroneal muscles. In a family originally described by <a href="#23" class="mim-tip-reference" title="Wilhelmsen, K. C., Blake, D. M., Lynch, T., Mabutas, J., De Vera, M., Neystat, M., Bernstein, M., Hirano, M., Gilliam, T. C., Murphy, P. L., Sola, M. D., Bonilla, E., Schotland, D. L., Hays, A. P., Rowland, L. P. <strong>Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy.</strong> Ann. Neurol. 39: 507-520, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619529</a>] [<a href="https://doi.org/10.1002/ana.410390413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8619529">Wilhelmsen et al. (1996)</a> with a myopathic form of scapuloperoneal syndrome (SPM; <a href="/entry/300695">300695</a>), <a href="#16" class="mim-tip-reference" title="Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M. <strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong> Am. J. Hum. Genet. 82: 208-213, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179901</a>] [<a href="https://doi.org/10.1016/j.ajhg.2007.09.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179901">Quinzii et al. (2008)</a> performed a genomewide scan with microsatellite markers and mapped the disorder to Xq26. All affected individuals carried a mutation in the FHL1 gene (W122S; <a href="#0001">300163.0001</a>) affecting the second LIM domain. <a href="#18" class="mim-tip-reference" title="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> stated that muscle biopsies from patients from the family reported by <a href="#16" class="mim-tip-reference" title="Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M. <strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong> Am. J. Hum. Genet. 82: 208-213, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179901</a>] [<a href="https://doi.org/10.1016/j.ajhg.2007.09.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179901">Quinzii et al. (2008)</a> had been reexamined and found to contain reducing bodies, suggesting that the phenotype in this family may represent a mild form of X-linked reducing body myopathy (<a href="/entry/300718">300718</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19181672+18179901+8619529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Myopathy with Postural Muscle Atrophy, X-linked</em></strong></p><p>
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In affected members of 2 families with an adult-onset scapuloaxioperoneal myopathy with bent spine syndrome characterized by specific atrophy of postural muscles and cardiac involvement (XMPMA; <a href="/entry/300696">300696</a>), <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> identified 2 different mutations in the FHL1 gene (<a href="#0002">300163.0002</a>; <a href="#0003">300163.0003</a>). There was muscle hypertrophy in the early stages of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18179888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C. <strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong> Neurology 73: 543-551, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687455</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b2a4b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687455">Schoser et al. (2009)</a> identified mutations in the C terminus of the FHL1 gene in 7 additional families with XMPMA (see, e.g., <a href="#0002">300163.0002</a>; <a href="#0013">300163.0013</a>; <a href="#0014">300163.0014</a>). Muscle biopsies showed absence of the FHL1 A isoform. No reducing bodies were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Emery-Dreifuss Muscular Dystrophy 6</em></strong></p><p>
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In affected members of 6 unrelated families with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see <a href="/entry/300696">300696</a>), <a href="#5" class="mim-tip-reference" title="Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G. <strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 85: 338-353, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19716112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19716112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19716112[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.ajhg.2009.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19716112">Gueneau et al. (2009)</a> identified 6 different mutations in the FHL1 gene (see, e.g., <a href="#0010">300163.0010</a>-<a href="#0012">300163.0012</a>). A patient with sporadic disease also had an FHL1 mutation. The mutations were preferentially located in the most distal exons 5 to 8 of FHL1 and impaired the 3 isoforms to various degrees. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19716112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Reducing Body Myopathy, X-linked</em></strong></p><p>
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In 2 unrelated girls with severe, early-onset reducing body myopathy (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> identified a de novo heterozygous mutation in the FHL1 gene (<a href="#0004">300163.0004</a> and <a href="#0005">300163.0005</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Two unrelated boys with childhood-onset reducing body myopathy (RBMX1B; <a href="/entry/300718">300718</a>) had hemizygous mutation in the FHL1 gene (<a href="#0006">300163.0006</a> and <a href="#0007">300163.0007</a>, respectively). <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> used a proteomic technique to identify FHL1 as the main protein component of the reducing bodies in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> reported 5 unrelated patients with sporadic severe early-onset X-linked reducing myopathy (<a href="/entry/300717">300717</a>) and reviewed their previously reported patients (<a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al., 2008</a>). All 5 patients had de novo mutations in the same residue of the second LIM domain of the FHL1 gene, affecting all 3 isoforms (H123Y, <a href="#0004">300163.0004</a>; H123L; <a href="#0015">300163.0015</a>, and H123Q; <a href="#0016">300163.0016</a>). Onset was in early childhood, and the disorder was rapidly progressive, leading to proximal muscle weakness and atrophy, loss of ambulation, contractures, and often respiratory insufficiency. There were 4 girls and 1 boy: the boy was more severely affected. Other features included scoliosis and spinal rigidity. Muscle biopsies showed FHL1-positive aggregates and reducing bodies. <a href="#18" class="mim-tip-reference" title="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> concluded that mutations in the second LIM domain of FHL1 result in reducing body myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18274675+19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Uruguay Faciocardiomusculoskeletal Syndrome</em></strong></p><p>
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In 3 affected males and 2 obligate female carriers from a 3-generation family with Uruguay faciocardiomusculoskeletal syndrome (FCMSU; <a href="/entry/300280">300280</a>) originally reported by <a href="#15" class="mim-tip-reference" title="Quadrelli, R., Vaglio, A., Reyno, S., Lemes, A., Salazar, D., Lachman, R. S., Wilcox, W. R. <strong>Uruguay facio-cardio-musculo-skeletal syndrome: a novel X-linked recessive disorder.</strong> Am. J. Med. Genet. 95: 247-265, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11102932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11102932</a>] [<a href="https://doi.org/10.1002/1096-8628(20001127)95:3<247::aid-ajmg12>3.0.co;2-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11102932">Quadrelli et al. (2000)</a>, <a href="#25" class="mim-tip-reference" title="Xue, Y., Schoser, B., Rao, A. R., Quadrelli, R., Vaglio, A., Rupp, V., Beichler, C., Nelson, S. F., Schapacher-Tilp, G., Windpassinger, C., Wilcox, W. R. <strong>Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.</strong> Circ. Cardiovasc. Genet. 9: 130-135, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26933038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26933038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26933038[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/10.1161/CIRCGENETICS.115.001193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26933038">Xue et al. (2016)</a> identified a hemizygous or heterozygous splice site mutation in the FHL1 gene (<a href="#0018">300163.0018</a>). The mutation, which was found by a combination of hemizygosity mapping and candidate gene exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient myoblasts showed skipping of exon 6, with the resulting primary structure of the protein identical to that of the FHL1C isoform. Western blot and immunohistochemical analysis of patient muscle showed almost complete absence of the FHL1A protein, and RT-PCR analysis showed a 4-fold increase in the expression of FHL1C. <a href="#25" class="mim-tip-reference" title="Xue, Y., Schoser, B., Rao, A. R., Quadrelli, R., Vaglio, A., Rupp, V., Beichler, C., Nelson, S. F., Schapacher-Tilp, G., Windpassinger, C., Wilcox, W. R. <strong>Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.</strong> Circ. Cardiovasc. Genet. 9: 130-135, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26933038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26933038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26933038[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/10.1161/CIRCGENETICS.115.001193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26933038">Xue et al. (2016)</a> postulated that the imbalance of FHL1 isoforms contributed to the unique features in this family. There was some phenotypic similarity to XMPMA, but the authors considered these to be distinct disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26933038+11102932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>18 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300163[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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122458140 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122458140;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=rs122458140" 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=rs122458140" 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=RCV000012303 OR RCV001562936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012303, RCV001562936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012303...</a>
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<p>In an Italian-American family with scapuloperoneal myopathy (<a href="/entry/300695">300695</a>), <a href="#16" class="mim-tip-reference" title="Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M. <strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong> Am. J. Hum. Genet. 82: 208-213, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179901</a>] [<a href="https://doi.org/10.1016/j.ajhg.2007.09.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179901">Quinzii et al. (2008)</a> demonstrated that the disorder was X-linked dominant and caused by a 365G-C transversion in exon 3 of the FHL1 gene, resulting in a trp122-to-ser substitution (W122S) in the second LIM domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18179901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> stated that muscle biopsies from patients from the family reported by <a href="#16" class="mim-tip-reference" title="Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M. <strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong> Am. J. Hum. Genet. 82: 208-213, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179901</a>] [<a href="https://doi.org/10.1016/j.ajhg.2007.09.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179901">Quinzii et al. (2008)</a> had been reexamined and found to contain reducing bodies, suggesting that the phenotype in this family may represent a mild form of X-linked reducing body myopathy (<a href="/entry/300718">300718</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18179901+19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Emmanuele, V., Kubota, A., Garcia-Diaz, B., Garone, C., Akman, H. O., Sanchez-Gutierrez, D., Escudero, L. M., Kariya, S., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M. <strong>Fhl1 W122S causes loss of protein function and late-onset mild myopathy.</strong> Hum. Molec. Genet. 24: 714-726, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25274776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25274776</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25274776[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/ddu490" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25274776">Emmanuele et al. (2015)</a> generated a knockin mouse model expressing the W122S mutation in Fhl1. Hemizygous male mutant mice and heterozygous female mutant mice had normal birth weight, early growth, and life span compared with wildtype. However, a slowly progressive decrease in forelimb grip strength, exercise capacity, and body weight was observed in hemizygous males starting at 7 to 10 months of age. Hindlimbs of hemizygous males maintained normal grip strength. Western blot analysis revealed loss of Fhl1 in hemizygous mutant muscle only after development of weakness. Histologic analysis revealed only mild structural abnormalities and no cytoplasmic inclusions in hemizygous mutant muscle at later ages. Heterozygous mutant females appeared unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25274776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Kubota, A., Juanola-Falgarona, M., Emmanuele, V., Sanchez-Quintero, M. J., Kariya, S., Sera, F., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M. <strong>Cardiomyopathy and altered integrin-actin signaling in Fhl1 mutant female mice.</strong> Hum. Molec. Genet. 28: 209-219, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30260394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30260394</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30260394[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/ddy299" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30260394">Kubota et al. (2019)</a> found that knockin female mice homozygous for the W122S mutation developed late-onset cardiomyopathy, but not overt skeletal myopathy. Histologic analysis revealed numerous extraordinarily enlarged rectangular nuclei in hearts of mutant female mice that were also present in human cardiac muscle from patients with X-linked scapuloperoneal myopathy. However, there was no aggregation of mutant Fhl1 protein, and Western blot analysis showed only trends toward a decreased amount of mutant protein in mouse heart muscle, indicating that loss of function in the mutant protein caused cardiac muscle dysfunction. Proteomic analysis showed that dysregulation of the integrin-actin pathway contributed to cardiac dysfunction in female mutant mice, and examination of heart and skeletal muscle in human patients also implicated alterations in the integrin-actin pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30260394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>.0002 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</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">rs122458141 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122458141;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=rs122458141" 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=rs122458141" 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=RCV000012304 OR RCV000725941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012304, RCV000725941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012304...</a>
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<p>In an extensive Austrian family in which males in 5 generations had a novel form of myopathy referred to as X-linked myopathy with postural muscle atrophy and generalized hypertrophy (XMPMA; <a href="/entry/300696">300696</a>), <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> detected a 672C-G transversion in the FHL1 gene that resulted in a cys224-to-trp (C224W) substitution in the fourth LIM domain of isoform A and in the nuclear localization signal of isoform B. Patients had muscle hypertrophy in the early stages, followed by postural muscle weakness and atrophy, increased serum creatine kinase, bent spine, and cardiomyopathy. The C224W mutation was predicted to disrupt the zinc-binding properties of FHL1A and to impair shuttling between nucleus and cytoplasm of FHL1B. Impairment of zinc binding may have reduced protein stability and structure. Isoform C was not affected, which the authors hypothesized may have resulted in the relatively mild phenotype; no females were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18179888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C. <strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong> Neurology 73: 543-551, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687455</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b2a4b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687455">Schoser et al. (2009)</a> reported 3 additional unrelated German families with XMPMA associated with the C224W mutation in the FHL1 gene. A fourth patient, later found to be distantly related to the Austrian family reported by <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a>, was also identified. The phenotype was similar to that reported by <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a>. The mutation is predicted to disrupt the fourth LIM domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19687455+18179888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</strong>
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SCAPULOPERONEAL MYOPATHY, X-LINKED DOMINANT, 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">rs1603271580 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603271580;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=rs1603271580" 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=rs1603271580" 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=RCV000012305 OR RCV000022828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012305, RCV000022828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012305...</a>
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<p>In a family of British origin with X-linked myopathy with postural muscle atrophy and generalized hypertrophy (XMPMA; <a href="/entry/300696">300696</a>), <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> identified a 3-bp insertion after nucleotide 381 of the FHL1 gene (381_382insATC), leading to the insertion of an isoleucine residue within the second LIM domain (phe127_thr128insile). The mutation affected all 3 FHL1 isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18179888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V. <strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong> Europ. J. Hum. Genet. 19: 1038-1044, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21629301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21629301</a>] [<a href="https://doi.org/10.1038/ejhg.2011.84" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21629301">Sarkozy et al. (2011)</a> reported 2 additional British families with the 381delATC mutation. These 2 families and the family reported by <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> shared the same haplotype, consistent with a founder effect. The family reported by <a href="#24" class="mim-tip-reference" title="Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S. <strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong> Am. J. Hum. Genet. 82: 88-99, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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.ajhg.2007.09.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18179888">Windpassinger et al. (2008)</a> included 4 males who presented in their thirties with progressive proximal muscle weakness causing walking difficulties and shoulder weakness. The disorder was progressive with at least 2 patients becoming wheelchair-bound. Other features included spinal rigidity, scapular winging, increased serum creatine kinase, and decreased vital respiratory capacity. One family reported by <a href="#17" class="mim-tip-reference" title="Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V. <strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong> Europ. J. Hum. Genet. 19: 1038-1044, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21629301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21629301</a>] [<a href="https://doi.org/10.1038/ejhg.2011.84" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21629301">Sarkozy et al. (2011)</a> included 11 affected individuals (5 women) spanning 5 generations. Three men had onset of symptoms in the second to third decade, with predominant progressive limb girdle weakness, mainly affecting the upper limbs, and scapular winging. They also had spinal rigidity and reduced lung function. An additional 3 deceased male family members were reported as being wheelchair-bound from their thirties, and dying in their late forties/early fifties of cardiorespiratory failure. Female mutation carriers had a slightly later onset of milder symptoms. In the other family reported by <a href="#17" class="mim-tip-reference" title="Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V. <strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong> Europ. J. Hum. Genet. 19: 1038-1044, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21629301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21629301</a>] [<a href="https://doi.org/10.1038/ejhg.2011.84" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21629301">Sarkozy et al. (2011)</a>, 5 males spanning 4 generations were affected. One had onset in young adulthood of progressive proximal upper and lower limb weakness, foot drop, and restricted neck movements with increased serum creatine kinase. Other family members reportedly had gait difficulties. <a href="#17" class="mim-tip-reference" title="Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V. <strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong> Europ. J. Hum. Genet. 19: 1038-1044, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21629301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21629301</a>] [<a href="https://doi.org/10.1038/ejhg.2011.84" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21629301">Sarkozy et al. (2011)</a> noted the heterogeneous phenotypes in these 3 families, although they all had an overall late presentation most consistent with XMPMA. However, the involvement of women in the second family was reminiscent of X-linked dominant scapuloperoneal myopathy (<a href="/entry/300695">300695</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18179888+21629301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY 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">rs122458142 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122458142;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=rs122458142" 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=rs122458142" 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=RCV000012306" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012306" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012306</a>
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<p>In a girl with severe, early-onset X-linked myopathy with reducing bodies (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> identified a de novo heterozygous 367C-T transition in the third coding exon of the FHL1 gene, resulting in a his123-to-tyr (H123Y) substitution in the second LIM domain involved in coordinating zinc binding. The H123Y mutation was predicted to result in complete disruption of the zinc-binding sites and collapse of the LIM domain. In vitro functional expression studies showed that the mutant protein initiated aggregation of the FHL1 protein, formed reducing bodies and trapped wildtype FHL1 into the inclusion bodies, consistent with a dominant-negative effect. The child lost ambulation by at age 3 years and had respiratory insufficiency. <a href="#18" class="mim-tip-reference" title="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> reported follow-up on the patient reported by <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a>. She had mildly delayed motor development, learning to walk at 18 months, but was never able to run or stand up from a sitting position. The disease progressed at age 2 years, with poor head control and neck weakness, leading wheelchair dependency at age 3. She had proximal muscle weakness, progressive spinal rigidity, and scoliosis. At age 8 years, she is ventilated continuously, has a gastrostomy tube, and has lost all antigravity strength except for her finger extensors. There is no apparent cardiac involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18274675+19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> reported another unrelated girl with a heterozygous H123Y mutation. She had onset before age 1.5 years of proximal muscle weakness and Gowers sign. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123L, <a href="#0015">300163.0015</a>; H123Q, <a href="#0016">300163.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a girl with severe, early-onset X-linked myopathy with reducing bodies (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> identified a de novo heterozygous 395G-T transversion in exon 3 of the FHL1 gene, resulting in a cys132-to-phe (C132F) substitution in the second LIM domain involved in coordinating zinc binding. The C132F mutation was predicted to result in complete disruption of the zinc-binding sites and collapse of the LIM domain. In vitro functional expression studies showed that the mutant protein initiated aggregation of the FHL1 protein, formed reducing bodies and trapped wildtype FHL1 into the inclusion bodies, consistent with a dominant-negative effect. The child lost ambulation by age 4.5 years and died of respiratory failure at age 6.5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122458144 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122458144;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=rs122458144" 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=rs122458144" 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 boy with X-linked reducing body myopathy with childhood onset (RBMX1B; <a href="/entry/300718">300718</a>), <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> identified a 457T-C transition in the FHL1 gene, resulting in a cys153-to-arg (C153R) substitution in the second zinc finger of the LIM2 domain. The patient's mother, who was heterozygous for the mutation, was less severely affected. The boy had onset of weakness at age 5 years, became ventilator-dependent by age 11 years, and developed cardiomyopathy at 18 years. A mutation in the same codon (C153Y; <a href="#0007">300163.0007</a>) was identified in an unrelated family with the same disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122458145 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122458145;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=rs122458145" 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=rs122458145" 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 boy with X-linked reducing myopathy with childhood onset (RBMX1B; <a href="/entry/300718">300718</a>), <a href="#19" class="mim-tip-reference" title="Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others. <strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong> J. Clin. Invest. 118: 904-912, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>] [<a href="https://doi.org/10.1172/JCI34450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18274675">Schessl et al. (2008)</a> identified a 458G-A transition in the FHL1 gene, resulting in a cys153-to-tyr (C153Y) substitution in the second zinc finger of the LIM2 domain. The patient's mother, who was heterozygous for the mutation, was less severely affected. The boy had onset of weakness and rigid spine symptoms at age 10 years, leading to loss of ambulation at age 16. A mutation in the same codon (C153R; <a href="#0006">300163.0006</a>) was identified in an unrelated family with the same disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122459146 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122459146;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=rs122459146" 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=rs122459146" 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 patient with fatal early-onset reducing body myopathy (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#22" class="mim-tip-reference" title="Shalaby, S., Hayashi, Y. K., Nonaka, I., Noguchi, S., Nishino, I. <strong>Novel FHL1 mutations in fatal and benign reducing body myopathy.</strong> Neurology 72: 375-376, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19171836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19171836</a>] [<a href="https://doi.org/10.1212/01.wnl.0000341311.84347.a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19171836">Shalaby et al. (2009)</a> identified a heterozygous 449G-A transition in the FHL1 gene, resulting in a cys150-to-tyr (C150Y) substitution in the second LIM domain. The patient had previously been reported by <a href="#6" class="mim-tip-reference" title="Kiyomoto, B. H., Murakami, N., Kobayashi, Y., Nihei, K., Tanaka, T., Takeshita, K., Nonaka, I. <strong>Fatal reducing body myopathy: ultrastructural and immnunohistochemical (sic) observations.</strong> J. Neurol. Sci. 128: 58-65, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7722535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7722535</a>] [<a href="https://doi.org/10.1016/0022-510x(94)00204-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7722535">Kiyomoto et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7722535+19171836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122459147 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122459147;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=rs122459147" 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=rs122459147" 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=RCV000012311" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012311" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012311</a>
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<p>In a mother and son with adult- and childhood-onset reducing body myopathy (RBMX1B; <a href="/entry/300718">300718</a>), respectively, <a href="#22" class="mim-tip-reference" title="Shalaby, S., Hayashi, Y. K., Nonaka, I., Noguchi, S., Nishino, I. <strong>Novel FHL1 mutations in fatal and benign reducing body myopathy.</strong> Neurology 72: 375-376, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19171836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19171836</a>] [<a href="https://doi.org/10.1212/01.wnl.0000341311.84347.a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19171836">Shalaby et al. (2009)</a> identified a 310T-C transition in the FHL1 gene, resulting in a cys104-to-arg (C104R) substitution in the second LIM domain. The family had previously been reported by <a href="#14" class="mim-tip-reference" title="Ohsawa, M., Liewluck, T., Ogata, K., Iizuka, T., Hayashi, Y., Nonaka, I., Sasaki, M., Nishino, I. <strong>Familial reducing body myopathy.</strong> Brain Dev. 29: 112-116, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16919903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16919903</a>] [<a href="https://doi.org/10.1016/j.braindev.2006.06.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16919903">Ohsawa et al. (2007)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16919903+19171836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122459148 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122459148;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=rs122459148" 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=rs122459148" 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=RCV000012312" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012312" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012312</a>
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<p>In 3 brothers from Saudi Arabia with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see <a href="/entry/300696">300696</a>), <a href="#5" class="mim-tip-reference" title="Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G. <strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 85: 338-353, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19716112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19716112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19716112[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.ajhg.2009.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19716112">Gueneau et al. (2009)</a> identified an 841T-G transversion in exon 8 of the FHL1 gene, resulting in a ter281-to-glu (X281E) substitution in the last codon. This change suppressed the termination codon and predicted a larger protein with 52 additional amino acids at the C terminus of the FHL1A isoform. The proband presented at age 10 years with stiff neck, and later developed scapular-peroneal weakness and atrophy, multiple joint contractures, and scoliosis. He also had dysphonia due to vocal cord palsy. At age 18 years, he was found to have cardiac involvement characterized by septal hypertrophy. Skeletal muscle biopsy showed dystrophic changes with no reducing bodies and markedly decreased FHL1A protein expression. In vitro studies of patient myoblasts showed a delay in myogenin (MYOG; <a href="/entry/159980">159980</a>) activation and myoblast fusion, without major impacts on sarcomere formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19716112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs122459149 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122459149;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=rs122459149" 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=rs122459149" 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=RCV000012313 OR RCV003511982" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012313, RCV003511982" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012313...</a>
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<p>In affected members of a large family with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see <a href="/entry/300696">300696</a>), <a href="#5" class="mim-tip-reference" title="Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G. <strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 85: 338-353, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19716112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19716112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19716112[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.ajhg.2009.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19716112">Gueneau et al. (2009)</a> identified a 625C-T transition in exon 6 of the FHL1 gene, resulting in a cys209-to-arg (C209R) substitution affecting a highly conserved cys residue of the LIM3 domain of the FHL1A and FHL1B isoforms. The proband presented at age 11 years with stiff neck. He later developed scapular and pelvic muscle weakness and atrophy, multiple joint contractures, scoliosis, and increased serum creatine kinase. At age 39, he had cardiac arrhythmias and cardiac hypertrophy; He died suddenly at age 51. Most affected family members had both cardiac disease and myopathy, although some had only isolated cardiac disease or myopathy. There were several affected females who were heterozygous for the mutation. Skeletal muscle biopsy of the proband showed a dystrophic pattern and moderately decreased FHL1 protein expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19716112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#7" class="mim-tip-reference" title="Knoblauch, H., Geier, C., Adams, S., Budde, B., Rudolph, A., Zacharias, U., Schulz-Menger, J., Spuler, A., Yaou, R. B., Nurnberg, P., Voit, T., Bonne, G., Spuler, S. <strong>Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.</strong> Ann. Neurol. 67: 136-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186852</a>] [<a href="https://doi.org/10.1002/ana.21839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20186852">Knoblauch et al. (2010)</a> identified the C209R mutation in 9 affected male members of a large 4-generation German family with EDMD6. Age at onset was in the first or second decade, and all had contractures and rigid spine. Five had hypertrophic cardiomyopathy, 2 had left ventricular hypertrophy with fibrosis and hypertension, 1 had apical myocardial thinning, and 1 had normal cardiac findings. Only 1 had conduction abnormalities, and only 1 had clear muscle weakness; most appeared muscular but not athletic. Two female carriers of the mutation had rigid spine symptoms, and 1 had left ventricular hypertrophy with hypertension. None of the patients was or became wheelchair-bound. Skeletal muscle biopsy from 3 patients showed cytoplasmic bodies, but not reducing bodies, and dystrophic features. Western blot analysis showed decreased expression of FHL1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1603273697 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603273697;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=rs1603273697" 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=rs1603273697" 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=RCV000012314" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012314" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012314</a>
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<p>In a man with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see <a href="/entry/300696">300696</a>), <a href="#5" class="mim-tip-reference" title="Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G. <strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong> Am. J. Hum. Genet. 85: 338-353, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19716112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19716112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19716112[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.ajhg.2009.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19716112">Gueneau et al. (2009)</a> identified a 1-bp insertion (817dup) in exon 8 of the FHL1 gene, resulting in a frameshift and premature termination affecting only the FHL1A isoform that lacks the last 2 cysteines of the LIM4 domain. He presented at age 6 years with elbow and Achilles tendon contractures, and later developed scapular and pelvic muscle weakness and atrophy. Other features included muscle hypertrophy, dysphonia due to vocal cord palsy, and increased serum creatine kinase. By age 30, he had cardiac septal hypertrophy and respiratory insufficiency; he died suddenly at age 31. Skeletal muscle biopsy showed myopathic changes and no reducing bodies. The patient's mother, who was heterozygous for the mutation, had isolated hypertrophic cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19716112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>.0013 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</strong>
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FHL1, VAL280MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606811 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606811;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=rs267606811" 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=rs267606811" 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=RCV000012315" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012315" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012315</a>
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<p>In 2 affected males from a German family with X-linked myopathy with postural muscle atrophy (XMPMA; <a href="/entry/300696">300696</a>), <a href="#20" class="mim-tip-reference" title="Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C. <strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong> Neurology 73: 543-551, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687455</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b2a4b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687455">Schoser et al. (2009)</a> identified an 838G-A transition in exon 5 of the FHL1 gene, resulting in a val280-to-met (V280M) substitution in isoform B. The mutation was not found in 247 control chromosomes. Both boys had onset at age 8 years of exercise-induced fatigue and Achilles tendon shortening, and later developed proximal lower leg weakness. No overt cardiac involvement was noted. A female carrier in the family was unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0014" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0014 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</strong>
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</h4>
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FHL1, IVS4DS, G-A, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200914 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200914;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=rs786200914" 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=rs786200914" 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=RCV000012316" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012316" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012316</a>
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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 affected males from a German family with X-linked myopathy with postural muscle atrophy (XMPMA; <a href="/entry/300696">300696</a>), <a href="#20" class="mim-tip-reference" title="Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C. <strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong> Neurology 73: 543-551, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687455</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b2a4b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687455">Schoser et al. (2009)</a> identified a G-to-A transition (c.688+1G-A) in the donor splice site of intron 4 of the FHL1 gene, resulting in the skipping of exon 4. The splice site is located after the second LIM domain, resulting in a truncated protein (Ala168GlyfsTer195) identical to isoform C, with the loss of both isoforms A and B. The proband had progressive Achilles tendon shortening since childhood, and developed a progressive aneurysm of the sinus of Valsalva since age 18. He had exercise-induced weakness and proximal muscle weakness. The other male patient presented with mild rigid spine syndrome, kyphoscoliosis, and Achilles tendon contractures since age 10 years. He was also noted to have a progressive aneurysm of the sinus of Valsalva since age 12. One female mutation carrier was noted with exercise-induced weakness and myalgia since age 40 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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</span>
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<div>
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<a id="0015" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0015 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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FHL1, HIS123LEU
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606812 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606812;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=rs267606812" 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=rs267606812" 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=RCV000012317" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012317" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012317</a>
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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 7-year-old girl with severe early-onset reducing body myopathy (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#18" class="mim-tip-reference" title="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> identified a heterozygous de novo 368A-T transversion in exon 4 of the FHL1 gene, resulting in a his123-to-leu (H123L) substitution in the second LIM domain. She had onset at age 4 years of frequent falls, difficulty walking, progressive proximal muscle weakness of the upper and lower limbs, and scoliosis. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123Y, <a href="#0004">300163.0004</a>; H123Q, <a href="#0016">300163.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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</span>
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<div>
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<div>
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<div>
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<a id="0016" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0016 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</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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<div style="float: left;">
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FHL1, HIS123GLN
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606813 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606813;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=rs267606813" 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=rs267606813" 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=RCV000012318 OR RCV001387579" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012318, RCV001387579" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012318...</a>
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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 3 unrelated patients, 2 girls and 1 boy, with severe early-onset reducing body myopathy (RBMX1A; <a href="/entry/300717">300717</a>), <a href="#18" class="mim-tip-reference" title="Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. <strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong> Brain 132: 452-464, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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/brain/awn325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181672">Schessl et al. (2009)</a> identified a de novo 369C-G transversion in exon 4 of the FHL1 gene, resulting in a his123-to-gln (H123Q) substitution in the second LIM domain. Onset ranged from 12 months to 4 years. Patients had frequent falls, progressive loss of ambulation by age 10 years, proximal muscle weakness in the upper and lower limbs, and contractures. Two patients had respiratory insufficiency. One had mild mitral insufficiency, and another had cardiac arrest at age 3 years. The boy had earlier onset and a more severe phenotype. The girls were heterozygous for the mutation. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123Y, <a href="#0004">300163.0004</a>; H123L, <a href="#0015">300163.0015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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</span>
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</div>
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<div>
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<div>
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<div>
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<a id="0017" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0017 REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE CHILDHOOD ONSET</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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<div style="float: left;">
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FHL1, 9-BP DEL, NT451
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012319" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012319" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012319</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a 16-year-old boy with late childhood onset of X-linked reducing body myopathy (RBMX1B; <a href="/entry/300718">300718</a>), <a href="#21" class="mim-tip-reference" title="Shalaby, S., Hayashi, Y. K., Goto, K., Ogawa, M., Nonaka, I., Noguchi, S., Nishino, I. <strong>Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1).</strong> Neuromusc. Disord. 18: 959-961, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18952429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18952429</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.09.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18952429">Shalaby et al. (2008)</a> identified a hemizygous in-frame 9-bp deletion (451delGTGACTTGC) in the FHL1 gene, resulting in the deletion of val151, thr152, and cys153, which affected a cysteine residue in the second LIM domain. The patient was a good runner during childhood and was noted to have scoliosis at age 13 years. He then developed progressive walking and running difficulties. By age 16, he had difficulty in bending his body and in neck flexion, atrophy and weakness of the proximal muscles, and joint contractures. He was diagnosed with rigid spine syndrome. Skeletal muscle biopsy showed intracytoplasmic inclusions, rimmed vacuoles, and decreased FHL1 protein levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18952429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0018" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0018 URUGUAY FACIOCARDIOMUSCULOSKELETAL SYNDROME (1 family)</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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FHL1, IVS5AS, A-G, -2
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1556639352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1556639352;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=rs1556639352" 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=rs1556639352" 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=RCV000515100" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515100" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515100</a>
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<p>In 3 affected males and 2 obligate female carriers from a 3-generation family with Uruguay faciocardiomusculoskeletal syndrome (FCMSU; <a href="/entry/300280">300280</a>) originally reported by <a href="#15" class="mim-tip-reference" title="Quadrelli, R., Vaglio, A., Reyno, S., Lemes, A., Salazar, D., Lachman, R. S., Wilcox, W. R. <strong>Uruguay facio-cardio-musculo-skeletal syndrome: a novel X-linked recessive disorder.</strong> Am. J. Med. Genet. 95: 247-265, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11102932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11102932</a>] [<a href="https://doi.org/10.1002/1096-8628(20001127)95:3<247::aid-ajmg12>3.0.co;2-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11102932">Quadrelli et al. (2000)</a>, <a href="#25" class="mim-tip-reference" title="Xue, Y., Schoser, B., Rao, A. R., Quadrelli, R., Vaglio, A., Rupp, V., Beichler, C., Nelson, S. F., Schapacher-Tilp, G., Windpassinger, C., Wilcox, W. R. <strong>Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.</strong> Circ. Cardiovasc. Genet. 9: 130-135, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26933038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26933038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26933038[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/10.1161/CIRCGENETICS.115.001193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26933038">Xue et al. (2016)</a> identified a hemizygous or heterozygous A-to-G transition (c.502-2A-G, NM_001449.4) in intron 5 of the FHL1 gene, resulting in a splice site alteration with the skipping of exon 6. The mutation, which was found by a combination of hemizygosity mapping and candidate gene exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Variant Server databases, as well as an in-house database. Patient myoblasts showed the skipping of exon 6, with the resulting primary structure of the protein identical to that of the FHL1C isoform. Western blot and immunohistochemical analysis of patient muscle showed almost complete absence of the FHL1A protein, and RT-PCR analysis showed a 4-fold increase in the expression of FHL1C. X-chromosome exome sequencing in 1 of the affected males also identified a variant of uncertain significance (T327I) in the BCORL1 gene (<a href="/entry/300688">300688</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26933038+11102932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Brown1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., Mitchell, C. A.
|
|
<strong>Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1: localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.</strong>
|
|
J. Biol. Chem. 274: 27083-27091, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
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[<a href="https://doi.org/10.1074/jbc.274.38.27083" target="_blank">Full Text</a>]
|
|
|
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Emmanuele2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Emmanuele, V., Kubota, A., Garcia-Diaz, B., Garone, C., Akman, H. O., Sanchez-Gutierrez, D., Escudero, L. M., Kariya, S., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M.
|
|
<strong>Fhl1 W122S causes loss of protein function and late-onset mild myopathy.</strong>
|
|
Hum. Molec. Genet. 24: 714-726, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25274776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25274776</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25274776[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=25274776" 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/ddu490" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Fimia2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fimia, G. M., De Cesare, D., Sassone-Corsi, P.
|
|
<strong>A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM.</strong>
|
|
Molec. Cell. Biol. 20: 8613-8622, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11046156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11046156</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11046156[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=11046156" 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.20.22.8613-8622.2000" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Greene1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Greene, W. K., Baker, E., Rabbitts, T. H., Kees, U. R.
|
|
<strong>Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.</strong>
|
|
Gene 232: 203-207, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352231</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1016/s0378-1119(99)00125-0" target="_blank">Full Text</a>]
|
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|
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|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gueneau2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G.
|
|
<strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 85: 338-353, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19716112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19716112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19716112[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=19716112" 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.ajhg.2009.07.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Kiyomoto1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kiyomoto, B. H., Murakami, N., Kobayashi, Y., Nihei, K., Tanaka, T., Takeshita, K., Nonaka, I.
|
|
<strong>Fatal reducing body myopathy: ultrastructural and immnunohistochemical (sic) observations.</strong>
|
|
J. Neurol. Sci. 128: 58-65, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7722535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7722535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7722535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0022-510x(94)00204-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Knoblauch2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Knoblauch, H., Geier, C., Adams, S., Budde, B., Rudolph, A., Zacharias, U., Schulz-Menger, J., Spuler, A., Yaou, R. B., Nurnberg, P., Voit, T., Bonne, G., Spuler, S.
|
|
<strong>Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.</strong>
|
|
Ann. Neurol. 67: 136-140, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186852" 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.21839" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Kubota2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kubota, A., Juanola-Falgarona, M., Emmanuele, V., Sanchez-Quintero, M. J., Kariya, S., Sera, F., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M.
|
|
<strong>Cardiomyopathy and altered integrin-actin signaling in Fhl1 mutant female mice.</strong>
|
|
Hum. Molec. Genet. 28: 209-219, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30260394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30260394</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30260394[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=30260394" 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/ddy299" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Lee1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, S. M. Y., Tsui, S. K. W., Chan, K. K., Garcia-Barcelo, M., Waye, M. M. Y., Fung, K. P., Liew, C. C., Lee, C. Y.
|
|
<strong>Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1).</strong>
|
|
Gene 216: 163-170, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9714789" 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/s0378-1119(98)00302-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Meertens2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meertens, L., Hafirassou, M. L., Couderc, T., Bonnet-Madin, L., Kril, V., Kummerer, B. M., Labeau, A., Brugier, A., Simon-Loriere, E., Burlaud-Gaillard, J., Doyen, C., Pezzi, L., and 14 others.
|
|
<strong>FHL1 is a major host factor for chikungunya virus infection.</strong>
|
|
Nature 574: 259-263, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31554973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31554973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31554973" 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/s41586-019-1578-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Morgan1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, M. J., Madgwick, A. J. A.
|
|
<strong>Slim defines a novel family of LIM-proteins expressed in skeletal muscle.</strong>
|
|
Biochem. Biophys. Res. Commun. 225: 632-638, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8753811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8753811</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8753811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1006/bbrc.1996.1222" target="_blank">Full Text</a>]
|
|
|
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|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
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<a id="12" class="mim-anchor"></a>
|
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<a id="Morgan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, M. J., Madgwick, A. J., Charleston, B., Pell, J. M., Loughna, P. T.
|
|
<strong>The developmental regulation of a novel muscle LIM-protein.</strong>
|
|
Biochem. Biophys. Res. Commun. 212: 840-846, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626119" 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/bbrc.1995.2045" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
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<a id="Ng2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Ng, E. K. O., Lee, S. M. Y., Li, H.-Y., Ngai, S.-M., Tsui, S. K. W., Waye, M. M. Y., Lee, C.-Y., Fung, K.-P.
|
|
<strong>Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of human LIM-only protein (FHL1).</strong>
|
|
J. Cell. Biochem. 82: 1-10, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11400158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11400158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11400158" 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/jcb.1110" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
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<a id="Ohsawa2007" class="mim-anchor"></a>
|
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<div class="">
|
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|
|
Ohsawa, M., Liewluck, T., Ogata, K., Iizuka, T., Hayashi, Y., Nonaka, I., Sasaki, M., Nishino, I.
|
|
<strong>Familial reducing body myopathy.</strong>
|
|
Brain Dev. 29: 112-116, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16919903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16919903</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16919903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.braindev.2006.06.010" target="_blank">Full Text</a>]
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<a id="Quadrelli2000" class="mim-anchor"></a>
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|
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Quadrelli, R., Vaglio, A., Reyno, S., Lemes, A., Salazar, D., Lachman, R. S., Wilcox, W. R.
|
|
<strong>Uruguay facio-cardio-musculo-skeletal syndrome: a novel X-linked recessive disorder.</strong>
|
|
Am. J. Med. Genet. 95: 247-265, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11102932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11102932</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11102932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/1096-8628(20001127)95:3<247::aid-ajmg12>3.0.co;2-2" target="_blank">Full Text</a>]
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|
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|
|
|
|
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|
|
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|
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<a id="Quinzii2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M.
|
|
<strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong>
|
|
Am. J. Hum. Genet. 82: 208-213, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179901</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18179901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2007.09.013" target="_blank">Full Text</a>]
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<a id="Sarkozy2011" class="mim-anchor"></a>
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Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V.
|
|
<strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong>
|
|
Europ. J. Hum. Genet. 19: 1038-1044, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21629301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21629301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21629301" 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.2011.84" target="_blank">Full Text</a>]
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|
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<a id="Schessl2009" class="mim-anchor"></a>
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Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others.
|
|
<strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong>
|
|
Brain 132: 452-464, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181672[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=19181672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1093/brain/awn325" target="_blank">Full Text</a>]
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|
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<a id="Schessl2008" class="mim-anchor"></a>
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|
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Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others.
|
|
<strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong>
|
|
J. Clin. Invest. 118: 904-912, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18274675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18274675</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18274675" 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/JCI34450" target="_blank">Full Text</a>]
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|
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|
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|
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<a id="Schoser2009" class="mim-anchor"></a>
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|
|
Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C.
|
|
<strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong>
|
|
Neurology 73: 543-551, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687455" 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/WNL.0b013e3181b2a4b3" target="_blank">Full Text</a>]
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|
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<a id="Shalaby2008" class="mim-anchor"></a>
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|
|
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|
|
Shalaby, S., Hayashi, Y. K., Goto, K., Ogawa, M., Nonaka, I., Noguchi, S., Nishino, I.
|
|
<strong>Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1).</strong>
|
|
Neuromusc. Disord. 18: 959-961, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18952429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18952429</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18952429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2008.09.012" target="_blank">Full Text</a>]
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<a id="22" class="mim-anchor"></a>
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<a id="Shalaby2009" class="mim-anchor"></a>
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Shalaby, S., Hayashi, Y. K., Nonaka, I., Noguchi, S., Nishino, I.
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<strong>Novel FHL1 mutations in fatal and benign reducing body myopathy.</strong>
|
|
Neurology 72: 375-376, 2009.
|
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19171836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19171836</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19171836" 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.0000341311.84347.a0" target="_blank">Full Text</a>]
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<a id="Wilhelmsen1996" class="mim-anchor"></a>
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<div class="">
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Wilhelmsen, K. C., Blake, D. M., Lynch, T., Mabutas, J., De Vera, M., Neystat, M., Bernstein, M., Hirano, M., Gilliam, T. C., Murphy, P. L., Sola, M. D., Bonilla, E., Schotland, D. L., Hays, A. P., Rowland, L. P.
|
|
<strong>Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy.</strong>
|
|
Ann. Neurol. 39: 507-520, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8619529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8619529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8619529" 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/ana.410390413" target="_blank">Full Text</a>]
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Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S.
|
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<strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong>
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Am. J. Hum. Genet. 82: 88-99, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18179888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18179888</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18179888[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=18179888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2007.09.004" target="_blank">Full Text</a>]
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<a id="Xue2016" class="mim-anchor"></a>
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Xue, Y., Schoser, B., Rao, A. R., Quadrelli, R., Vaglio, A., Rupp, V., Beichler, C., Nelson, S. F., Schapacher-Tilp, G., Windpassinger, C., Wilcox, W. R.
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<strong>Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.</strong>
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Circ. Cardiovasc. Genet. 9: 130-135, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26933038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26933038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26933038[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=26933038" 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/CIRCGENETICS.115.001193" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Ada Hamosh - updated : 03/27/2020
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Bao Lige - updated : 07/22/2019<br>Cassandra L. Kniffin - updated : 10/31/2017<br>Patricia A. Hartz - updated : 3/20/2015<br>Cassandra L. Kniffin - updated : 3/21/2012<br>Cassandra L. Kniffin - updated : 5/11/2010<br>Cassandra L. Kniffin - updated : 12/29/2009<br>Cassandra L. Kniffin - updated : 10/5/2009<br>Cassandra L. Kniffin - updated : 3/13/2009<br>Cassandra L. Kniffin - updated : 6/16/2008<br>Victor A. McKusick - updated : 2/19/2008<br>Patricia A. Hartz - updated : 1/16/2003<br>Carol A. Bocchini - updated : 12/1/1998
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Patti M. Sherman : 12/1/1998
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carol : 09/09/2022<br>alopez : 06/21/2022<br>alopez : 03/27/2020<br>mgross : 07/22/2019<br>mgross : 07/22/2019<br>carol : 10/31/2017<br>ckniffin : 10/31/2017<br>alopez : 09/19/2016<br>carol : 10/30/2015<br>mgross : 4/6/2015<br>mcolton : 3/20/2015<br>carol : 9/11/2013<br>carol : 11/28/2012<br>carol : 3/21/2012<br>ckniffin : 3/21/2012<br>wwang : 5/13/2010<br>ckniffin : 5/11/2010<br>alopez : 3/4/2010<br>carol : 2/16/2010<br>wwang : 1/15/2010<br>ckniffin : 12/29/2009<br>wwang : 10/9/2009<br>wwang : 10/9/2009<br>ckniffin : 10/5/2009<br>wwang : 3/24/2009<br>ckniffin : 3/13/2009<br>wwang : 6/18/2008<br>ckniffin : 6/16/2008<br>alopez : 2/21/2008<br>alopez : 2/21/2008<br>terry : 2/19/2008<br>alopez : 12/17/2004<br>terry : 7/19/2004<br>cwells : 1/21/2003<br>terry : 1/16/2003<br>terry : 12/2/1998<br>carol : 12/1/1998<br>carol : 12/1/1998
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</span>
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<div class="container visible-print-block">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300163
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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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FOUR-AND-A-HALF LIM DOMAINS 1; FHL1
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</span>
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</h3>
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</div>
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<br />
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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SLIM1<br />
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FHL1A<br />
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KYOT, MOUSE, HOMOLOG OF
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</span>
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</h4>
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</div>
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<br />
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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FHL1B, 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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SLIMMER, INCLUDED<br />
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FHL1C, INCLUDED
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</span>
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</div>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: FHL1</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> 773729007;
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xq26.3
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Genomic coordinates <span class="small">(GRCh38)</span> : X:136,146,702-136,211,359 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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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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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="6">
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<span class="mim-font">
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Xq26.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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?Uruguay faciocardiomusculoskeletal syndrome
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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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300280
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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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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Emery-Dreifuss muscular dystrophy 6, X-linked
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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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300696
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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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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Myopathy, X-linked, with postural muscle atrophy
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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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300696
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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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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset
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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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300717
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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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X-linked dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Reducing body myopathy, X-linked 1b, with late childhood or adult onset
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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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300718
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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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X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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Scapuloperoneal myopathy, X-linked dominant
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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300695
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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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X-linked dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>LIM proteins, named for 'LIN11, ISL1, and MEC3,' are defined by the possession of a highly conserved double zinc finger motif called the LIM domain.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Morgan et al. (1995) identified a partial human SLIM1 cDNA. They found that SLIM1 is a developmentally regulated protein that is expressed in human skeletal muscle but not in a variety of other tissues. By searching sequence databases with the partial SLIM1 cDNA isolated by Morgan et al. (1995), Morgan and Madgwick (1996) identified human cDNAs encoding the complete SLIM1 amino acid sequence. The predicted 280-amino acid protein contains 4 LIM domains and a novel single zinc finger domain in the N-terminal region. By Northern blot analysis, SLIM1 is expressed as a 2.3-kb mRNA in human masseter muscle. </p><p>By Northern blot analysis, Greene et al. (1999) found a 2.5-kb transcript strongly expressed in skeletal muscle and to a lesser extent in heart. Significantly lower expression was observed in prostate, testis, ovary, small and large intestine, placenta, and lung, while barely detectable expression was seen in spleen, thymus, and pancreas. No expression was detected in leukocytes, brain, liver, and kidney. A second transcript of about 1.3-kb was found at low levels in testis, heart, and skeletal muscle. </p><p>Using a sequence derived from the 5-prime end of inositol polyphosphate 5-phosphatase (INPP5A; 600106) as a probe, Brown et al. (1999) cloned FHL1, which they called SLIM1, from a bone marrow cDNA library. Sequence analysis revealed that each LIM domain is separated by 8 intervening amino acids. SLIM1 shares 47% sequence identity with SLIM3 (FHL2; 602633) and 45% identity with SLIM2 (FHL3; 602790). SLIM1 shares no homology with INPP5A except for a 16-nucleotide stretch contained within the probe used to screen the library. </p><p>Brown et al. (1999) also cloned an alternatively spliced isoform, which they called SLIMMER (FHL1B), that differs from SLIM1 with a 200-bp insertion that causes a frameshift. The deduced protein contains 323 amino acids and has a calculated molecular mass of 34 kD. It contains an N-terminal zinc finger followed by 3 LIM domains identical to SLIM1, and a novel 93-amino acid C terminus that contains 3 bipartite nuclear localization signals (NLS) followed by a leucine-rich nuclear export sequence (NES). Northern blot analysis revealed a 2.4-kb SLIMMER transcript expressed at high levels in skeletal muscle and at lower levels in heart, colon, prostate, and small intestine. A 4.4-kb transcript was also observed in skeletal muscle and colon. Western blot analysis of skeletal muscle using isoform-specific antibodies revealed endogenous expression of both a 34-kD SLIMMER protein and a 32-kD SLIM1 protein. Fluorescence-tagged SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in transfected COS-7 cells, while fluorescence-tagged SLIMMER was predominantly nuclear. Truncation mutants revealed that the first NLS mediated SLIMMER nuclear localization. </p><p>Brown et al. (1999) found that endogenous Slim1 showed diffuse cytoplasmic staining and low nuclear staining in mouse myoblasts. Following differentiation into multinucleated myotubes, Slim1 staining became exclusively cytoplasmic. SLIMMER showed prominent nuclear staining of myoblasts and exclusively cytoplasmic staining of myotubes. The leucine-rich NES was required for the export of Slimmer from the nucleus of mouse myoblasts to the cytoplasm of differentiated myotubes. By Northern blot analysis of mouse tissues, Fimia et al. (2000) determined that Fhl1 was the only Fhl transcript tested that was expressed in a wide range of tissues. High levels were present in heart, skeletal muscle, ovary, kidney, lung, and brain, and much lower levels were found in spleen, liver, adrenal gland, testis, and pituitary. </p><p>Ng et al. (2001) identified a third alternatively spliced isoform of the FHL1 gene, which they designated FHL1C. The deduced 195-residue FHL1C isoform contains a single zinc finger and 2 tandem repeats of LIM domains at the N terminus, followed by a putative RBPJ-binding region at the C terminus. FHL1C lacks exon 4, resulting in a frameshift in the 3-prime coding region and absence of a putative nuclear export sequence coded by exon 4b. Northern blot and RT-PCR analysis showed that FHL1C was specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1A. Low levels of FHL1C expression were observed in aorta, left atrium, and left and right ventricles. Western blot analysis detected a 20-kD corresponding to FHL1C in human skeletal muscle and heart. Unlike FHL1B, which is located primarily in the nucleus, FHL1C was localized both in the nucleus and cytoplasm of mammalian cells. </p>
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Greene et al. (1999) determined that the FHL1 gene contains at least 5 exons and spans over 3.6 kb. All 4 introns disrupt the coding region at regular intervals near the start of each complete LIM motif, implying that exon duplication may be responsible for the tandem LIM domain repeats. </p><p>The FHL1A isoform contains exons 1 through 5, FHL1B contains exons 1, 2, 3, 4, 4b, and 5, and FHL1C contains 1, 2, 3, and 5 (Ng et al., 2001). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By somatic cell hybrid mapping, FISH, and radiation hybrid mapping, Lee et al. (1998) mapped the FHL1 gene to chromosome Xq27.2. By FISH, Greene et al. (1999) mapped the FHL1 gene to Xq26. In connection with myopathy caused by mutations in the FHL1 gene, Windpassinger et al. (2008) indirectly mapped the FHL1 gene to Xq26.3. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Meertens et al. (2019) identified FHL1 as a host factor that is required for chikungunya virus permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression resulted in the inhibition of infection by several chikungunya strains and o'nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 in cells that do not normally express it promoted chikungunya infection. Meertens et al. (2019) found that FHL1 interacts directly with the hypervariable domain of the nsP3 protein of chikungunya and is essential for the replication of viral RNA. FHL1 is highly expressed in chikungunya target cells and is particularly abundant in muscles. Dermal fibroblasts and muscle cells derived from patients with Emery-Dreifuss muscular dystrophy (see 300696) that lacked functional FHL1 were resistant to chikungunya infection. Furthermore, chikungunya infection was undetectable in Fhl1-knockout mice. Meertens et al. (2019) concluded that their study showed that FHL1 is a key factor expressed by the host that enables chikungunya virus infection. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Scapuloperoneal Myopathy, X-linked</em></strong></p><p>
|
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Scapuloperoneal syndrome encompasses heterogeneous neuromuscular disorders characterized by weakness in the shoulder girdle and peroneal muscles. In a family originally described by Wilhelmsen et al. (1996) with a myopathic form of scapuloperoneal syndrome (SPM; 300695), Quinzii et al. (2008) performed a genomewide scan with microsatellite markers and mapped the disorder to Xq26. All affected individuals carried a mutation in the FHL1 gene (W122S; 300163.0001) affecting the second LIM domain. Schessl et al. (2009) stated that muscle biopsies from patients from the family reported by Quinzii et al. (2008) had been reexamined and found to contain reducing bodies, suggesting that the phenotype in this family may represent a mild form of X-linked reducing body myopathy (300718). </p><p><strong><em>Myopathy with Postural Muscle Atrophy, X-linked</em></strong></p><p>
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In affected members of 2 families with an adult-onset scapuloaxioperoneal myopathy with bent spine syndrome characterized by specific atrophy of postural muscles and cardiac involvement (XMPMA; 300696), Windpassinger et al. (2008) identified 2 different mutations in the FHL1 gene (300163.0002; 300163.0003). There was muscle hypertrophy in the early stages of the disorder. </p><p>Schoser et al. (2009) identified mutations in the C terminus of the FHL1 gene in 7 additional families with XMPMA (see, e.g., 300163.0002; 300163.0013; 300163.0014). Muscle biopsies showed absence of the FHL1 A isoform. No reducing bodies were identified. </p><p><strong><em>Emery-Dreifuss Muscular Dystrophy 6</em></strong></p><p>
|
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In affected members of 6 unrelated families with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see 300696), Gueneau et al. (2009) identified 6 different mutations in the FHL1 gene (see, e.g., 300163.0010-300163.0012). A patient with sporadic disease also had an FHL1 mutation. The mutations were preferentially located in the most distal exons 5 to 8 of FHL1 and impaired the 3 isoforms to various degrees. </p><p><strong><em>Reducing Body Myopathy, X-linked</em></strong></p><p>
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In 2 unrelated girls with severe, early-onset reducing body myopathy (RBMX1A; 300717), Schessl et al. (2008) identified a de novo heterozygous mutation in the FHL1 gene (300163.0004 and 300163.0005, respectively). </p><p>Two unrelated boys with childhood-onset reducing body myopathy (RBMX1B; 300718) had hemizygous mutation in the FHL1 gene (300163.0006 and 300163.0007, respectively). Schessl et al. (2008) used a proteomic technique to identify FHL1 as the main protein component of the reducing bodies in these patients. </p><p>Schessl et al. (2009) reported 5 unrelated patients with sporadic severe early-onset X-linked reducing myopathy (300717) and reviewed their previously reported patients (Schessl et al., 2008). All 5 patients had de novo mutations in the same residue of the second LIM domain of the FHL1 gene, affecting all 3 isoforms (H123Y, 300163.0004; H123L; 300163.0015, and H123Q; 300163.0016). Onset was in early childhood, and the disorder was rapidly progressive, leading to proximal muscle weakness and atrophy, loss of ambulation, contractures, and often respiratory insufficiency. There were 4 girls and 1 boy: the boy was more severely affected. Other features included scoliosis and spinal rigidity. Muscle biopsies showed FHL1-positive aggregates and reducing bodies. Schessl et al. (2009) concluded that mutations in the second LIM domain of FHL1 result in reducing body myopathy. </p><p><strong><em>Uruguay Faciocardiomusculoskeletal Syndrome</em></strong></p><p>
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In 3 affected males and 2 obligate female carriers from a 3-generation family with Uruguay faciocardiomusculoskeletal syndrome (FCMSU; 300280) originally reported by Quadrelli et al. (2000), Xue et al. (2016) identified a hemizygous or heterozygous splice site mutation in the FHL1 gene (300163.0018). The mutation, which was found by a combination of hemizygosity mapping and candidate gene exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient myoblasts showed skipping of exon 6, with the resulting primary structure of the protein identical to that of the FHL1C isoform. Western blot and immunohistochemical analysis of patient muscle showed almost complete absence of the FHL1A protein, and RT-PCR analysis showed a 4-fold increase in the expression of FHL1C. Xue et al. (2016) postulated that the imbalance of FHL1 isoforms contributed to the unique features in this family. There was some phenotypic similarity to XMPMA, but the authors considered these to be distinct disorders. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>18 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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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>.0001 SCAPULOPERONEAL MYOPATHY, X-LINKED 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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FHL1, TRP122SER
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<br />
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SNP: rs122458140,
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ClinVar: RCV000012303, RCV001562936
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</span>
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</div>
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<span class="mim-text-font">
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<p>In an Italian-American family with scapuloperoneal myopathy (300695), Quinzii et al. (2008) demonstrated that the disorder was X-linked dominant and caused by a 365G-C transversion in exon 3 of the FHL1 gene, resulting in a trp122-to-ser substitution (W122S) in the second LIM domain of the protein. </p><p>Schessl et al. (2009) stated that muscle biopsies from patients from the family reported by Quinzii et al. (2008) had been reexamined and found to contain reducing bodies, suggesting that the phenotype in this family may represent a mild form of X-linked reducing body myopathy (300718). </p><p>Emmanuele et al. (2015) generated a knockin mouse model expressing the W122S mutation in Fhl1. Hemizygous male mutant mice and heterozygous female mutant mice had normal birth weight, early growth, and life span compared with wildtype. However, a slowly progressive decrease in forelimb grip strength, exercise capacity, and body weight was observed in hemizygous males starting at 7 to 10 months of age. Hindlimbs of hemizygous males maintained normal grip strength. Western blot analysis revealed loss of Fhl1 in hemizygous mutant muscle only after development of weakness. Histologic analysis revealed only mild structural abnormalities and no cytoplasmic inclusions in hemizygous mutant muscle at later ages. Heterozygous mutant females appeared unaffected. </p><p>Kubota et al. (2019) found that knockin female mice homozygous for the W122S mutation developed late-onset cardiomyopathy, but not overt skeletal myopathy. Histologic analysis revealed numerous extraordinarily enlarged rectangular nuclei in hearts of mutant female mice that were also present in human cardiac muscle from patients with X-linked scapuloperoneal myopathy. However, there was no aggregation of mutant Fhl1 protein, and Western blot analysis showed only trends toward a decreased amount of mutant protein in mouse heart muscle, indicating that loss of function in the mutant protein caused cardiac muscle dysfunction. Proteomic analysis showed that dysregulation of the integrin-actin pathway contributed to cardiac dysfunction in female mutant mice, and examination of heart and skeletal muscle in human patients also implicated alterations in the integrin-actin pathway. </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 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</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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FHL1, CYS224TRP
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<br />
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SNP: rs122458141,
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ClinVar: RCV000012304, RCV000725941
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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 an extensive Austrian family in which males in 5 generations had a novel form of myopathy referred to as X-linked myopathy with postural muscle atrophy and generalized hypertrophy (XMPMA; 300696), Windpassinger et al. (2008) detected a 672C-G transversion in the FHL1 gene that resulted in a cys224-to-trp (C224W) substitution in the fourth LIM domain of isoform A and in the nuclear localization signal of isoform B. Patients had muscle hypertrophy in the early stages, followed by postural muscle weakness and atrophy, increased serum creatine kinase, bent spine, and cardiomyopathy. The C224W mutation was predicted to disrupt the zinc-binding properties of FHL1A and to impair shuttling between nucleus and cytoplasm of FHL1B. Impairment of zinc binding may have reduced protein stability and structure. Isoform C was not affected, which the authors hypothesized may have resulted in the relatively mild phenotype; no females were affected. </p><p>Schoser et al. (2009) reported 3 additional unrelated German families with XMPMA associated with the C224W mutation in the FHL1 gene. A fourth patient, later found to be distantly related to the Austrian family reported by Windpassinger et al. (2008), was also identified. The phenotype was similar to that reported by Windpassinger et al. (2008). The mutation is predicted to disrupt the fourth LIM domain. </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>.0003 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</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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SCAPULOPERONEAL MYOPATHY, X-LINKED 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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FHL1, 3-BP INS, 381ATC
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<br />
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SNP: rs1603271580,
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ClinVar: RCV000012305, RCV000022828
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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 of British origin with X-linked myopathy with postural muscle atrophy and generalized hypertrophy (XMPMA; 300696), Windpassinger et al. (2008) identified a 3-bp insertion after nucleotide 381 of the FHL1 gene (381_382insATC), leading to the insertion of an isoleucine residue within the second LIM domain (phe127_thr128insile). The mutation affected all 3 FHL1 isoforms. </p><p>Sarkozy et al. (2011) reported 2 additional British families with the 381delATC mutation. These 2 families and the family reported by Windpassinger et al. (2008) shared the same haplotype, consistent with a founder effect. The family reported by Windpassinger et al. (2008) included 4 males who presented in their thirties with progressive proximal muscle weakness causing walking difficulties and shoulder weakness. The disorder was progressive with at least 2 patients becoming wheelchair-bound. Other features included spinal rigidity, scapular winging, increased serum creatine kinase, and decreased vital respiratory capacity. One family reported by Sarkozy et al. (2011) included 11 affected individuals (5 women) spanning 5 generations. Three men had onset of symptoms in the second to third decade, with predominant progressive limb girdle weakness, mainly affecting the upper limbs, and scapular winging. They also had spinal rigidity and reduced lung function. An additional 3 deceased male family members were reported as being wheelchair-bound from their thirties, and dying in their late forties/early fifties of cardiorespiratory failure. Female mutation carriers had a slightly later onset of milder symptoms. In the other family reported by Sarkozy et al. (2011), 5 males spanning 4 generations were affected. One had onset in young adulthood of progressive proximal upper and lower limb weakness, foot drop, and restricted neck movements with increased serum creatine kinase. Other family members reportedly had gait difficulties. Sarkozy et al. (2011) noted the heterogeneous phenotypes in these 3 families, although they all had an overall late presentation most consistent with XMPMA. However, the involvement of women in the second family was reminiscent of X-linked dominant scapuloperoneal myopathy (300695). </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>.0004 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</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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FHL1, HIS123TYR
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<br />
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SNP: rs122458142,
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ClinVar: RCV000012306
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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 girl with severe, early-onset X-linked myopathy with reducing bodies (RBMX1A; 300717), Schessl et al. (2008) identified a de novo heterozygous 367C-T transition in the third coding exon of the FHL1 gene, resulting in a his123-to-tyr (H123Y) substitution in the second LIM domain involved in coordinating zinc binding. The H123Y mutation was predicted to result in complete disruption of the zinc-binding sites and collapse of the LIM domain. In vitro functional expression studies showed that the mutant protein initiated aggregation of the FHL1 protein, formed reducing bodies and trapped wildtype FHL1 into the inclusion bodies, consistent with a dominant-negative effect. The child lost ambulation by at age 3 years and had respiratory insufficiency. Schessl et al. (2009) reported follow-up on the patient reported by Schessl et al. (2008). She had mildly delayed motor development, learning to walk at 18 months, but was never able to run or stand up from a sitting position. The disease progressed at age 2 years, with poor head control and neck weakness, leading wheelchair dependency at age 3. She had proximal muscle weakness, progressive spinal rigidity, and scoliosis. At age 8 years, she is ventilated continuously, has a gastrostomy tube, and has lost all antigravity strength except for her finger extensors. There is no apparent cardiac involvement. </p><p>Schessl et al. (2009) reported another unrelated girl with a heterozygous H123Y mutation. She had onset before age 1.5 years of proximal muscle weakness and Gowers sign. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123L, 300163.0015; H123Q, 300163.0016). </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FHL1, CYS132PHE
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|
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<br />
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|
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SNP: rs122458143,
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|
|
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|
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ClinVar: RCV000012307, RCV004585997
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with severe, early-onset X-linked myopathy with reducing bodies (RBMX1A; 300717), Schessl et al. (2008) identified a de novo heterozygous 395G-T transversion in exon 3 of the FHL1 gene, resulting in a cys132-to-phe (C132F) substitution in the second LIM domain involved in coordinating zinc binding. The C132F mutation was predicted to result in complete disruption of the zinc-binding sites and collapse of the LIM domain. In vitro functional expression studies showed that the mutant protein initiated aggregation of the FHL1 protein, formed reducing bodies and trapped wildtype FHL1 into the inclusion bodies, consistent with a dominant-negative effect. The child lost ambulation by age 4.5 years and died of respiratory failure at age 6.5 years. </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>.0006 REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE 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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FHL1, CYS153ARG
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<br />
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|
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SNP: rs122458144,
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|
|
ClinVar: RCV000012308, RCV001813974, RCV003511980
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with X-linked reducing body myopathy with childhood onset (RBMX1B; 300718), Schessl et al. (2008) identified a 457T-C transition in the FHL1 gene, resulting in a cys153-to-arg (C153R) substitution in the second zinc finger of the LIM2 domain. The patient's mother, who was heterozygous for the mutation, was less severely affected. The boy had onset of weakness at age 5 years, became ventilator-dependent by age 11 years, and developed cardiomyopathy at 18 years. A mutation in the same codon (C153Y; 300163.0007) was identified in an unrelated family with the same disorder. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<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>.0007 REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE CHILDHOOD ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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FHL1, CYS153TYR
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<br />
|
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|
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SNP: rs122458145,
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|
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ClinVar: RCV000012309, RCV003511981
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with X-linked reducing myopathy with childhood onset (RBMX1B; 300718), Schessl et al. (2008) identified a 458G-A transition in the FHL1 gene, resulting in a cys153-to-tyr (C153Y) substitution in the second zinc finger of the LIM2 domain. The patient's mother, who was heterozygous for the mutation, was less severely affected. The boy had onset of weakness and rigid spine symptoms at age 10 years, leading to loss of ambulation at age 16. A mutation in the same codon (C153R; 300163.0006) was identified in an unrelated family with the same disorder. </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>.0008 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY 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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FHL1, CYS150TYR
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<br />
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SNP: rs122459146,
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ClinVar: RCV000012310, RCV001851803
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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 patient with fatal early-onset reducing body myopathy (RBMX1A; 300717), Shalaby et al. (2009) identified a heterozygous 449G-A transition in the FHL1 gene, resulting in a cys150-to-tyr (C150Y) substitution in the second LIM domain. The patient had previously been reported by Kiyomoto et al. (1995). </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>.0009 REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE CHILDHOOD OR ADULT ONSET</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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FHL1, CYS104ARG
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<br />
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SNP: rs122459147,
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ClinVar: RCV000012311
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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 mother and son with adult- and childhood-onset reducing body myopathy (RBMX1B; 300718), respectively, Shalaby et al. (2009) identified a 310T-C transition in the FHL1 gene, resulting in a cys104-to-arg (C104R) substitution in the second LIM domain. The family had previously been reported by Ohsawa et al. (2007). </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>
|
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<span class="mim-font">
|
|
<strong>.0010 EMERY-DREIFUSS MUSCULAR DYSTROPHY 6</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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FHL1, TER281GLU
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<br />
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SNP: rs122459148,
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ClinVar: RCV000012312
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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 3 brothers from Saudi Arabia with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see 300696), Gueneau et al. (2009) identified an 841T-G transversion in exon 8 of the FHL1 gene, resulting in a ter281-to-glu (X281E) substitution in the last codon. This change suppressed the termination codon and predicted a larger protein with 52 additional amino acids at the C terminus of the FHL1A isoform. The proband presented at age 10 years with stiff neck, and later developed scapular-peroneal weakness and atrophy, multiple joint contractures, and scoliosis. He also had dysphonia due to vocal cord palsy. At age 18 years, he was found to have cardiac involvement characterized by septal hypertrophy. Skeletal muscle biopsy showed dystrophic changes with no reducing bodies and markedly decreased FHL1A protein expression. In vitro studies of patient myoblasts showed a delay in myogenin (MYOG; 159980) activation and myoblast fusion, without major impacts on sarcomere formation. </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>.0011 EMERY-DREIFUSS MUSCULAR DYSTROPHY 6</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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FHL1, CYS209ARG
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<br />
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SNP: rs122459149,
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ClinVar: RCV000012313, RCV003511982
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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 large family with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see 300696), Gueneau et al. (2009) identified a 625C-T transition in exon 6 of the FHL1 gene, resulting in a cys209-to-arg (C209R) substitution affecting a highly conserved cys residue of the LIM3 domain of the FHL1A and FHL1B isoforms. The proband presented at age 11 years with stiff neck. He later developed scapular and pelvic muscle weakness and atrophy, multiple joint contractures, scoliosis, and increased serum creatine kinase. At age 39, he had cardiac arrhythmias and cardiac hypertrophy; He died suddenly at age 51. Most affected family members had both cardiac disease and myopathy, although some had only isolated cardiac disease or myopathy. There were several affected females who were heterozygous for the mutation. Skeletal muscle biopsy of the proband showed a dystrophic pattern and moderately decreased FHL1 protein expression. </p><p>Knoblauch et al. (2010) identified the C209R mutation in 9 affected male members of a large 4-generation German family with EDMD6. Age at onset was in the first or second decade, and all had contractures and rigid spine. Five had hypertrophic cardiomyopathy, 2 had left ventricular hypertrophy with fibrosis and hypertension, 1 had apical myocardial thinning, and 1 had normal cardiac findings. Only 1 had conduction abnormalities, and only 1 had clear muscle weakness; most appeared muscular but not athletic. Two female carriers of the mutation had rigid spine symptoms, and 1 had left ventricular hypertrophy with hypertension. None of the patients was or became wheelchair-bound. Skeletal muscle biopsy from 3 patients showed cytoplasmic bodies, but not reducing bodies, and dystrophic features. Western blot analysis showed decreased expression of FHL1. </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 EMERY-DREIFUSS MUSCULAR DYSTROPHY 6</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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FHL1, 1-BP INS, NT817
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<br />
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SNP: rs1603273697,
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ClinVar: RCV000012314
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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 man with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see 300696), Gueneau et al. (2009) identified a 1-bp insertion (817dup) in exon 8 of the FHL1 gene, resulting in a frameshift and premature termination affecting only the FHL1A isoform that lacks the last 2 cysteines of the LIM4 domain. He presented at age 6 years with elbow and Achilles tendon contractures, and later developed scapular and pelvic muscle weakness and atrophy. Other features included muscle hypertrophy, dysphonia due to vocal cord palsy, and increased serum creatine kinase. By age 30, he had cardiac septal hypertrophy and respiratory insufficiency; he died suddenly at age 31. Skeletal muscle biopsy showed myopathic changes and no reducing bodies. The patient's mother, who was heterozygous for the mutation, had isolated hypertrophic cardiomyopathy. </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>.0013 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</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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FHL1, VAL280MET
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<br />
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SNP: rs267606811,
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ClinVar: RCV000012315
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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 affected males from a German family with X-linked myopathy with postural muscle atrophy (XMPMA; 300696), Schoser et al. (2009) identified an 838G-A transition in exon 5 of the FHL1 gene, resulting in a val280-to-met (V280M) substitution in isoform B. The mutation was not found in 247 control chromosomes. Both boys had onset at age 8 years of exercise-induced fatigue and Achilles tendon shortening, and later developed proximal lower leg weakness. No overt cardiac involvement was noted. A female carrier in the family was unaffected. </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 MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY</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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FHL1, IVS4DS, G-A, +1
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<br />
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|
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SNP: rs786200914,
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|
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ClinVar: RCV000012316
|
|
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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 2 affected males from a German family with X-linked myopathy with postural muscle atrophy (XMPMA; 300696), Schoser et al. (2009) identified a G-to-A transition (c.688+1G-A) in the donor splice site of intron 4 of the FHL1 gene, resulting in the skipping of exon 4. The splice site is located after the second LIM domain, resulting in a truncated protein (Ala168GlyfsTer195) identical to isoform C, with the loss of both isoforms A and B. The proband had progressive Achilles tendon shortening since childhood, and developed a progressive aneurysm of the sinus of Valsalva since age 18. He had exercise-induced weakness and proximal muscle weakness. The other male patient presented with mild rigid spine syndrome, kyphoscoliosis, and Achilles tendon contractures since age 10 years. He was also noted to have a progressive aneurysm of the sinus of Valsalva since age 12. One female mutation carrier was noted with exercise-induced weakness and myalgia since age 40 years. </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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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
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FHL1, HIS123LEU
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<br />
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|
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SNP: rs267606812,
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|
|
|
ClinVar: RCV000012317
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl with severe early-onset reducing body myopathy (RBMX1A; 300717), Schessl et al. (2009) identified a heterozygous de novo 368A-T transversion in exon 4 of the FHL1 gene, resulting in a his123-to-leu (H123L) substitution in the second LIM domain. She had onset at age 4 years of frequent falls, difficulty walking, progressive proximal muscle weakness of the upper and lower limbs, and scoliosis. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123Y, 300163.0004; H123Q, 300163.0016). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 REDUCING BODY MYOPATHY, X-LINKED 1, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FHL1, HIS123GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606813,
|
|
|
|
|
|
|
|
ClinVar: RCV000012318, RCV001387579
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated patients, 2 girls and 1 boy, with severe early-onset reducing body myopathy (RBMX1A; 300717), Schessl et al. (2009) identified a de novo 369C-G transversion in exon 4 of the FHL1 gene, resulting in a his123-to-gln (H123Q) substitution in the second LIM domain. Onset ranged from 12 months to 4 years. Patients had frequent falls, progressive loss of ambulation by age 10 years, proximal muscle weakness in the upper and lower limbs, and contractures. Two patients had respiratory insufficiency. One had mild mitral insufficiency, and another had cardiac arrest at age 3 years. The boy had earlier onset and a more severe phenotype. The girls were heterozygous for the mutation. Mutations affecting the same FHL1 codon have also been reported in this phenotype (H123Y, 300163.0004; H123L, 300163.0015). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE CHILDHOOD ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FHL1, 9-BP DEL, NT451
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000012319
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 16-year-old boy with late childhood onset of X-linked reducing body myopathy (RBMX1B; 300718), Shalaby et al. (2008) identified a hemizygous in-frame 9-bp deletion (451delGTGACTTGC) in the FHL1 gene, resulting in the deletion of val151, thr152, and cys153, which affected a cysteine residue in the second LIM domain. The patient was a good runner during childhood and was noted to have scoliosis at age 13 years. He then developed progressive walking and running difficulties. By age 16, he had difficulty in bending his body and in neck flexion, atrophy and weakness of the proximal muscles, and joint contractures. He was diagnosed with rigid spine syndrome. Skeletal muscle biopsy showed intracytoplasmic inclusions, rimmed vacuoles, and decreased FHL1 protein levels. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 URUGUAY FACIOCARDIOMUSCULOSKELETAL SYNDROME (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FHL1, IVS5AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1556639352,
|
|
|
|
|
|
|
|
ClinVar: RCV000515100
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected males and 2 obligate female carriers from a 3-generation family with Uruguay faciocardiomusculoskeletal syndrome (FCMSU; 300280) originally reported by Quadrelli et al. (2000), Xue et al. (2016) identified a hemizygous or heterozygous A-to-G transition (c.502-2A-G, NM_001449.4) in intron 5 of the FHL1 gene, resulting in a splice site alteration with the skipping of exon 6. The mutation, which was found by a combination of hemizygosity mapping and candidate gene exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Variant Server databases, as well as an in-house database. Patient myoblasts showed the skipping of exon 6, with the resulting primary structure of the protein identical to that of the FHL1C isoform. Western blot and immunohistochemical analysis of patient muscle showed almost complete absence of the FHL1A protein, and RT-PCR analysis showed a 4-fold increase in the expression of FHL1C. X-chromosome exome sequencing in 1 of the affected males also identified a variant of uncertain significance (T327I) in the BCORL1 gene (300688). </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
|
|
<ol>
|
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<li>
|
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<p class="mim-text-font">
|
|
Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., Mitchell, C. A.
|
|
<strong>Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1: localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.</strong>
|
|
J. Biol. Chem. 274: 27083-27091, 1999.
|
|
|
|
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|
[PubMed: 10480922]
|
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|
|
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[Full Text: https://doi.org/10.1074/jbc.274.38.27083]
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</p>
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</li>
|
|
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<li>
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<p class="mim-text-font">
|
|
Emmanuele, V., Kubota, A., Garcia-Diaz, B., Garone, C., Akman, H. O., Sanchez-Gutierrez, D., Escudero, L. M., Kariya, S., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M.
|
|
<strong>Fhl1 W122S causes loss of protein function and late-onset mild myopathy.</strong>
|
|
Hum. Molec. Genet. 24: 714-726, 2015.
|
|
|
|
|
|
[PubMed: 25274776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu490]
|
|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fimia, G. M., De Cesare, D., Sassone-Corsi, P.
|
|
<strong>A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM.</strong>
|
|
Molec. Cell. Biol. 20: 8613-8622, 2000.
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|
[PubMed: 11046156]
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|
|
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|
[Full Text: https://doi.org/10.1128/MCB.20.22.8613-8622.2000]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Greene, W. K., Baker, E., Rabbitts, T. H., Kees, U. R.
|
|
<strong>Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.</strong>
|
|
Gene 232: 203-207, 1999.
|
|
|
|
|
|
[PubMed: 10352231]
|
|
|
|
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|
[Full Text: https://doi.org/10.1016/s0378-1119(99)00125-0]
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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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Gueneau, L., Bertrand, A. T., Jais, J.-P., Salih, M. A., Stojkovic, T., Wehnert, M., Hoeltzenbein, M., Spuler, S., Saitoh, S., Verschueren, A., Tranchant, C., Beuvin, M., Lacene, E., Romero, N. B., Heath, S., Zelenika, D., Voit, T., Eymard, B., Yaou, R. B., Bonne, G.
|
|
<strong>Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 85: 338-353, 2009.
|
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|
|
|
|
[PubMed: 19716112]
|
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|
|
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[Full Text: https://doi.org/10.1016/j.ajhg.2009.07.015]
|
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</p>
|
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</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Kiyomoto, B. H., Murakami, N., Kobayashi, Y., Nihei, K., Tanaka, T., Takeshita, K., Nonaka, I.
|
|
<strong>Fatal reducing body myopathy: ultrastructural and immnunohistochemical (sic) observations.</strong>
|
|
J. Neurol. Sci. 128: 58-65, 1995.
|
|
|
|
|
|
[PubMed: 7722535]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(94)00204-2]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Knoblauch, H., Geier, C., Adams, S., Budde, B., Rudolph, A., Zacharias, U., Schulz-Menger, J., Spuler, A., Yaou, R. B., Nurnberg, P., Voit, T., Bonne, G., Spuler, S.
|
|
<strong>Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.</strong>
|
|
Ann. Neurol. 67: 136-140, 2010.
|
|
|
|
|
|
[PubMed: 20186852]
|
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|
|
[Full Text: https://doi.org/10.1002/ana.21839]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kubota, A., Juanola-Falgarona, M., Emmanuele, V., Sanchez-Quintero, M. J., Kariya, S., Sera, F., Homma, S., Tanji, K., Quinzii, C. M., Hirano, M.
|
|
<strong>Cardiomyopathy and altered integrin-actin signaling in Fhl1 mutant female mice.</strong>
|
|
Hum. Molec. Genet. 28: 209-219, 2019.
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|
|
|
|
[PubMed: 30260394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddy299]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Lee, S. M. Y., Tsui, S. K. W., Chan, K. K., Garcia-Barcelo, M., Waye, M. M. Y., Fung, K. P., Liew, C. C., Lee, C. Y.
|
|
<strong>Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1).</strong>
|
|
Gene 216: 163-170, 1998.
|
|
|
|
|
|
[PubMed: 9714789]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(98)00302-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Meertens, L., Hafirassou, M. L., Couderc, T., Bonnet-Madin, L., Kril, V., Kummerer, B. M., Labeau, A., Brugier, A., Simon-Loriere, E., Burlaud-Gaillard, J., Doyen, C., Pezzi, L., and 14 others.
|
|
<strong>FHL1 is a major host factor for chikungunya virus infection.</strong>
|
|
Nature 574: 259-263, 2019.
|
|
|
|
|
|
[PubMed: 31554973]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-019-1578-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan, M. J., Madgwick, A. J. A.
|
|
<strong>Slim defines a novel family of LIM-proteins expressed in skeletal muscle.</strong>
|
|
Biochem. Biophys. Res. Commun. 225: 632-638, 1996.
|
|
|
|
|
|
[PubMed: 8753811]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1996.1222]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan, M. J., Madgwick, A. J., Charleston, B., Pell, J. M., Loughna, P. T.
|
|
<strong>The developmental regulation of a novel muscle LIM-protein.</strong>
|
|
Biochem. Biophys. Res. Commun. 212: 840-846, 1995.
|
|
|
|
|
|
[PubMed: 7626119]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1995.2045]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ng, E. K. O., Lee, S. M. Y., Li, H.-Y., Ngai, S.-M., Tsui, S. K. W., Waye, M. M. Y., Lee, C.-Y., Fung, K.-P.
|
|
<strong>Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of human LIM-only protein (FHL1).</strong>
|
|
J. Cell. Biochem. 82: 1-10, 2001.
|
|
|
|
|
|
[PubMed: 11400158]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/jcb.1110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohsawa, M., Liewluck, T., Ogata, K., Iizuka, T., Hayashi, Y., Nonaka, I., Sasaki, M., Nishino, I.
|
|
<strong>Familial reducing body myopathy.</strong>
|
|
Brain Dev. 29: 112-116, 2007.
|
|
|
|
|
|
[PubMed: 16919903]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.braindev.2006.06.010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quadrelli, R., Vaglio, A., Reyno, S., Lemes, A., Salazar, D., Lachman, R. S., Wilcox, W. R.
|
|
<strong>Uruguay facio-cardio-musculo-skeletal syndrome: a novel X-linked recessive disorder.</strong>
|
|
Am. J. Med. Genet. 95: 247-265, 2000.
|
|
|
|
|
|
[PubMed: 11102932]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1096-8628(20001127)95:3<247::aid-ajmg12>3.0.co;2-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M.
|
|
<strong>X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1.</strong>
|
|
Am. J. Hum. Genet. 82: 208-213, 2008.
|
|
|
|
|
|
[PubMed: 18179901]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2007.09.013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sarkozy, A., Windpassinger, C., Hudson, J., Dougan, C. F., Lecky, B., Hilton-Jones, D., Eagle, M., Charlton, R., Barresi, R., Lochmuller, H., Bushby, K., Straub, V.
|
|
<strong>Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.</strong>
|
|
Europ. J. Hum. Genet. 19: 1038-1044, 2011.
|
|
|
|
|
|
[PubMed: 21629301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2011.84]
|
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|
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</p>
|
|
</li>
|
|
|
|
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|
|
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|
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Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others.
|
|
<strong>Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.</strong>
|
|
Brain 132: 452-464, 2009.
|
|
|
|
|
|
[PubMed: 19181672]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awn325]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
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Schessl, J., Zou, Y., McGrath, M. J., Cowling, B. S., Maiti, B., Chin, S. S., Sewry, C., Battini, R., Hu, Y., Cottle, D. L., Rosenblatt, M., Spruce, L., and 9 others.
|
|
<strong>Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.</strong>
|
|
J. Clin. Invest. 118: 904-912, 2008.
|
|
|
|
|
|
[PubMed: 18274675]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI34450]
|
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|
|
</p>
|
|
</li>
|
|
|
|
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|
|
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|
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Schoser, B., Goebel, H. H., Janisch, I., Quasthoff, S., Rother, J., Bergmann, M., Muller-Felber, W., Windpassinger, C.
|
|
<strong>Consequences of mutations within the C terminus of the FHL1 gene.</strong>
|
|
Neurology 73: 543-551, 2009.
|
|
|
|
|
|
[PubMed: 19687455]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e3181b2a4b3]
|
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</p>
|
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</li>
|
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|
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|
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Shalaby, S., Hayashi, Y. K., Goto, K., Ogawa, M., Nonaka, I., Noguchi, S., Nishino, I.
|
|
<strong>Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1).</strong>
|
|
Neuromusc. Disord. 18: 959-961, 2008.
|
|
|
|
|
|
[PubMed: 18952429]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2008.09.012]
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</p>
|
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</li>
|
|
|
|
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|
|
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|
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Shalaby, S., Hayashi, Y. K., Nonaka, I., Noguchi, S., Nishino, I.
|
|
<strong>Novel FHL1 mutations in fatal and benign reducing body myopathy.</strong>
|
|
Neurology 72: 375-376, 2009.
|
|
|
|
|
|
[PubMed: 19171836]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000341311.84347.a0]
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</p>
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</li>
|
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Wilhelmsen, K. C., Blake, D. M., Lynch, T., Mabutas, J., De Vera, M., Neystat, M., Bernstein, M., Hirano, M., Gilliam, T. C., Murphy, P. L., Sola, M. D., Bonilla, E., Schotland, D. L., Hays, A. P., Rowland, L. P.
|
|
<strong>Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy.</strong>
|
|
Ann. Neurol. 39: 507-520, 1996.
|
|
|
|
|
|
[PubMed: 8619529]
|
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|
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|
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[Full Text: https://doi.org/10.1002/ana.410390413]
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</p>
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</li>
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Windpassinger, C., Schoser, B., Straub, V., Hochmeister, S., Noor, A., Lohberger, B., Farra, N., Petek, E., Schwarzbraun, T., Ofner, L., Loscher, W. N., Wagner, K., Lochmuller, H., Vincent, J. B., Quasthoff, S.
|
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<strong>An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.</strong>
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Am. J. Hum. Genet. 82: 88-99, 2008.
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[PubMed: 18179888]
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[Full Text: https://doi.org/10.1016/j.ajhg.2007.09.004]
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Xue, Y., Schoser, B., Rao, A. R., Quadrelli, R., Vaglio, A., Rupp, V., Beichler, C., Nelson, S. F., Schapacher-Tilp, G., Windpassinger, C., Wilcox, W. R.
|
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<strong>Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.</strong>
|
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Circ. Cardiovasc. Genet. 9: 130-135, 2016.
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[PubMed: 26933038]
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[Full Text: https://doi.org/10.1161/CIRCGENETICS.115.001193]
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</div>
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</body>
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</html>
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