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<title>
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Entry
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- *161650 - NEBULIN; NEB
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*161650</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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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" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li 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/161650">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li 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=ENSG00000183091;t=ENST00000397345" 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=4703" 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=161650" 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=ENSG00000183091;t=ENST00000397345" 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_001164507,NM_001164508,NM_001271208,NM_004543,XM_005246590,XM_005246591,XM_005246592,XM_005246593,XM_005246594,XM_005246596,XM_005246597,XM_005246598,XM_005246599,XM_005246601,XM_005246602,XM_005246604,XM_005246606,XM_005246608,XM_005246610,XM_005246611,XM_005246612,XM_005246613,XM_005246615,XM_005246616,XM_005246617,XM_006712541,XM_006712542,XM_011511225,XM_011511226,XM_011511227,XM_017004177,XM_017004178,XM_017004179,XM_017004180,XM_017004181,XM_017004182,XM_017004183,XM_017004184,XM_017004185,XM_047444477,XM_047444478,XM_047444479,XM_047444481,XM_047444482,XM_047444483,XM_047444484,XM_047444485" 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_001164508" 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=161650" 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=01196&isoform_id=01196_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/NEB" 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/34997,189115,806562,1205990,1205991,4416404,16552551,30046564,33604106,38649085,62822082,62822429,111494061,113816037,116283490,119631904,119631905,119631906,119631907,119631908,119631909,119631910,119631911,193788497,221043056,221043294,221043316,530370423,530370425,530370427,530370429,530370431,530370435,530370437,530370439,530370441,530370445,530370447,530370451,530370455,530370459,530370463,530370465,530370467,530370469,530370473,530370475,530370477,578804367,578804369,767918245,767918247,767918249,1034614177,1034614180,1034614190,1034614194,1034614197,1034614200,1034614206,1034614209,1034614212,1527146894,1677537680,1886411695,1935006424,2217328268,2217328271,2217328286,2217328294,2217328296,2217328298,2217328300,2217328303,2462573578,2462573580,2462573582,2462573584,2462573586,2462573588,2462573590,2462573592,2462573594,2462573596,2462573598,2462573600,2462573602,2462573604,2462573606,2462573608,2462573610,2462573612,2462573614,2462573616,2462573618,2462573620,2462573622,2462573624,2462573626,2462573628,2462573630,2462573632,2462573634,2462573636,2462573638,2462573640,2462573642,2462573644,2462573646,2462573648,2462573650,2462573652,2462573654,2462573656,2462573658,2737873913" 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/P20929" 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=4703" 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=ENSG00000183091;t=ENST00000397345" 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=NEB" 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=NEB" 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+4703" 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/NEB" 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:4703" 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/4703" 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=chr2&hgg_gene=ENST00000427231.7&hgg_start=151485339&hgg_end=151734476&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7720" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/neb" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=161650[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=161650[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/NEB/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/ENSG00000183091" 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=NEB" 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=NEB" 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=NEB" 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/NEB" 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=NEB&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/PA31530" 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:7720" 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:97292" 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/NEB#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:97292" 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/4703/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002137/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4703" 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-041111-216" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:161650" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4703" 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=NEB&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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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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161650
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NEBULIN; NEB
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NEB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NEB</a></em></strong>
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Cytogenetic location: <a href="/geneMap/2/688?start=-3&limit=10&highlight=688">2q23.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:151485339-151734476&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'})">2:151,485,339-151,734,476</a> </span>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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<strong>Gene-Phenotype Relationships</strong>
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View Clinical Synopses
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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2q23.3
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Arthrogryposis multiplex congenita 6
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<a href="/entry/619334"> 619334 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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Nemaline myopathy 2, autosomal recessive
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<span class="mim-font">
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<a href="/entry/256030"> 256030 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/161650" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/161650" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</div>
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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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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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<p>Nebulin is a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein and its size varies from 600 to 800 kD in a manner that is tissue-, species-, and developmental stage-specific (<a href="#19" class="mim-tip-reference" title="Stedman, H., Browning, K., Oliver, N., Oronzi-Scott, M., Fischbeck, K., Sarkar, S., Sylvester, J., Schmickel, R., Wang, K. <strong>Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2.</strong> Genomics 2: 1-7, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2838409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2838409</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90102-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2838409">Stedman et al., 1988</a>). A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs (<a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10051637+2838409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Cloning and Expression</strong>
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<span class="mim-text-font">
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<p>Using polyclonal nebulin antisera to screen a cDNA expression library, <a href="#19" class="mim-tip-reference" title="Stedman, H., Browning, K., Oliver, N., Oronzi-Scott, M., Fischbeck, K., Sarkar, S., Sylvester, J., Schmickel, R., Wang, K. <strong>Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2.</strong> Genomics 2: 1-7, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2838409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2838409</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90102-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2838409">Stedman et al. (1988)</a> isolated 2 separate human fetal muscle cDNA clones. Both cDNAs detected a 25-kb skeletal muscle RNA transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2838409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Zeviani, M., Darras, B. T., Rizzuto, R., Salviati, G., Betto, R., Bonilla, E., Miranda, A. F., Du, J., Samitt, C., Dickson, G., Walsh, F. S., DiMauro, S., Francke, U., Schon, E. A. <strong>Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32.</strong> Genomics 2: 249-256, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3397062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3397062</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90009-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3397062">Zeviani et al. (1988)</a> also isolated 2 nonoverlapping cDNAs encoding human nebulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3397062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#24" class="mim-tip-reference" title="Wang, K., Knipfer, M., Huang, Q.-Q., van Heerden, A., Hsu, L. C.-L., Gutierrez, G., Quian, X.-L., Stedman, H. <strong>Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture: sequence motifs and affinity profiles of tandem repeats and terminal SH3.</strong> J. Biol. Chem. 271: 4304-4314, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626778</a>] [<a href="https://doi.org/10.1074/jbc.271.8.4304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8626778">Wang et al. (1996)</a> isolated 2 partial cDNA sequences of fetal skeletal muscle nebulin, and <a href="#6" class="mim-tip-reference" title="Labeit, S., Kolmerer, B. <strong>The complete primary structure of human nebulin and its correlation to muscle structure.</strong> J. Molec. Biol. 248: 308-315, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7739042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7739042</a>] [<a href="https://doi.org/10.1016/s0022-2836(95)80052-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7739042">Labeit and Kolmerer (1995)</a> obtained the nearly identical sequence of a complete 20.8-kb cDNA encoding adult nebulin (the few changes may be due to sequencing errors or polymorphisms). The 6,669-residue (773 kD) predicted protein contains 185 copies of 35-amino acid modules that can be classified into 7 types. <a href="#6" class="mim-tip-reference" title="Labeit, S., Kolmerer, B. <strong>The complete primary structure of human nebulin and its correlation to muscle structure.</strong> J. Molec. Biol. 248: 308-315, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7739042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7739042</a>] [<a href="https://doi.org/10.1016/s0022-2836(95)80052-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7739042">Labeit and Kolmerer (1995)</a> suggested alternative splicing as the explanation for developmental or tissue-specific size variants of nebulin. They speculated that features at the C-terminal end of the protein, including an SH3 domain (which is also found in yeast actin-binding protein), may anchor nebulin to the Z disc of the sarcomere. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8626778+7739042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K. <strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong> Europ. J. Hum. Genet. 12: 744-751, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266303</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266303">Donner et al. (2004)</a> found that the NEB protein contains an N-terminal glutamic acid-rich domain followed by a tropomodulin-binding region; a central region containing simple repeats, super repeats of 7 simple repeats, and a desmin-binding region; and a C-terminal titin- and myopalladin-binding region, which anchors the protein in the Z disc. They also determined that the NEB gene encodes numerous splice variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Gene Structure</strong>
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<p><a href="#4" class="mim-tip-reference" title="Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K. <strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong> Europ. J. Hum. Genet. 12: 744-751, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266303</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266303">Donner et al. (2004)</a> determined that the nebulin gene contains 183 exons in a 249-kb genomic region. The translation initiation codon is in exon 3, and the stop codon and the 3-prime untranslated region are in exon 183. The central region of the gene harbors an approximately 8.2-kb region spanning 8 exons, which is duplicated twice (exons 82 to 89, exons 90 to 97, and exons 98 to 105). The duplicated segments are 99% identical. Introns 89, 97, and 105 contain LINE-2 repetitive elements. There are 4 regions with alternatively spliced exons: exons 63 to 66, 82 to 105, 143 and 144, and 166 to 177. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#19" class="mim-tip-reference" title="Stedman, H., Browning, K., Oliver, N., Oronzi-Scott, M., Fischbeck, K., Sarkar, S., Sylvester, J., Schmickel, R., Wang, K. <strong>Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2.</strong> Genomics 2: 1-7, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2838409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2838409</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90102-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2838409">Stedman et al. (1988)</a> localized 2 human nebulin cDNAs from fetal muscle to chromosome 2. By hybridization to DNA isolated from rodent-human cell hybrids, <a href="#27" class="mim-tip-reference" title="Zeviani, M., Darras, B. T., Rizzuto, R., Salviati, G., Betto, R., Bonilla, E., Miranda, A. F., Du, J., Samitt, C., Dickson, G., Walsh, F. S., DiMauro, S., Francke, U., Schon, E. A. <strong>Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32.</strong> Genomics 2: 249-256, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3397062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3397062</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90009-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3397062">Zeviani et al. (1988)</a> assigned the human nebulin gene to chromosome 2 and, by in situ hybridization, sublocalized it to region 2q31-q32. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3397062+2838409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 fluorescence in situ hybridization, <a href="#11" class="mim-tip-reference" title="Limongi, M. Z., Pelliccia, F., Rocchi, A. <strong>Assignment of the human nebulin gene (NEB) to chromosome band 2q24.2 and the alpha-1 (III) collagen gene (COL3A1) to chromosome band 2q32.2 by in situ hybridization: the FRA2G common fragile site lies between the two genes in the 2q31 band.</strong> Cytogenet. Cell Genet. 77: 259-260, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9284930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9284930</a>] [<a href="https://doi.org/10.1159/000134590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9284930">Limongi et al. (1997)</a> demonstrated that the NEB gene is located on 2q24.2, whereas the gene encoding the alpha-1 chain of type III collagen (<a href="/entry/120180">120180</a>) is located on 2q32.2. The FRA2 gene common fragile site lies between the 2 genes in the 2q31 band. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9284930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.</strong> Europ. J. Hum. Genet. 5: 229-234, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9359044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9359044</a>]" pmid="9359044">Pelin et al. (1997)</a> used radiation hybrid mapping to reassign the nebulin gene close to the microsatellite marker D2S2236 on 2q22. They concluded that the nebulin gene resides within the candidate region for NEM2 (<a href="/entry/256030">256030</a>), a form of autosomal recessive nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9359044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 5 different series of recombinant inbred strains, <a href="#18" class="mim-tip-reference" title="Schurr, E., Skamene, E., Gros, P. <strong>Mapping of the gene coding for the muscle protein nebulin (Neb) to the proximal region of mouse chromosome 2.</strong> Cytogenet. Cell Genet. 57: 214-216, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1683831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1683831</a>] [<a href="https://doi.org/10.1159/000133150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1683831">Schurr et al. (1991)</a> mapped the mouse nebulin gene to proximal chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1683831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 many tissues, actin monomers polymerize into actin (thin) filaments of precise lengths. Using RNA interference, <a href="#13" class="mim-tip-reference" title="McElhinny, A. S., Schwach, C., Valichnac, M., Mount-Patrick, S., Gregorio, C. C. <strong>Nebulin regulates the assembly and lengths of the thin filaments in striated muscle.</strong> J. Cell Biol. 170: 947-957, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16157704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16157704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16157704[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/10.1083/jcb.200502158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16157704">McElhinny et al. (2005)</a> demonstrated that nebulin behaves as a 'molecular ruler' in rat cardiac and skeletal muscle. Upon nebulin knockdown, preexisting thin filaments in cultured rat cardiac muscle cells were dramatically elongated from their pointed ends; the barbed ends were unaffected. When the thin filaments were depolymerized, myocytes with decreased nebulin levels reassembled them to unrestricted lengths. Finally, knockdown of nebulin in rat skeletal myotubes revealed its involvement in myofibrillogenesis. <a href="#13" class="mim-tip-reference" title="McElhinny, A. S., Schwach, C., Valichnac, M., Mount-Patrick, S., Gregorio, C. C. <strong>Nebulin regulates the assembly and lengths of the thin filaments in striated muscle.</strong> J. Cell Biol. 170: 947-957, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16157704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16157704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16157704[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/10.1083/jcb.200502158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16157704">McElhinny et al. (2005)</a> concluded that nebulin has a role in specifying and maintaining the length of actin thin filaments in striated muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16157704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In mice, <a href="#20" class="mim-tip-reference" title="Takano, K., Watanabe-Takano, H., Suetsugu, S., Kurita, S., Tsujita, K., Kimura, S., Karatsu, T., Takenawa, T., Endo, T. <strong>Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.</strong> Science 330: 1536-1540, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21148390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21148390</a>] [<a href="https://doi.org/10.1126/science.1197767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21148390">Takano et al. (2010)</a> found that Igf1 (<a href="/entry/147440">147440</a>)-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-Wasp (<a href="/entry/605056">605056</a>) at the Z bands of myofibrils by interfering with glycogen synthase kinase-3-beta (GSK3B; <a href="/entry/605004">605004</a>). Although N-Wasp is known to be an activator of the Arp2/3 complex (see <a href="/entry/604221">604221</a>) to form branched actin filaments, the nebulin-N-Wasp complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-Wasp was required for Igf1-induced muscle hypertrophy. <a href="#20" class="mim-tip-reference" title="Takano, K., Watanabe-Takano, H., Suetsugu, S., Kurita, S., Tsujita, K., Kimura, S., Karatsu, T., Takenawa, T., Endo, T. <strong>Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.</strong> Science 330: 1536-1540, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21148390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21148390</a>] [<a href="https://doi.org/10.1126/science.1197767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21148390">Takano et al. (2010)</a> concluded that their findings presented the mechanisms of IGF1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21148390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Nemaline Myopathy 2</em></strong></p><p>
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In affected members of 5 unrelated families of different ethnic origins with congenital autosomal recessive nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>), <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> identified 6 different mutations in the NEB gene (<a href="#0001">161650.0001</a>-<a href="#0006">161650.0006</a>). All of the mutations were located within the M162-M185 segment. In 2 families with consanguineous parents, the patients were homozygous for point mutations. In 1 family with nonconsanguineous parents, the affected sibs were compound heterozygotes for 2 different mutations, and in 2 further families with 1 detected mutation each, haplotypes were compatible with compound heterozygosity. Immunofluorescence studies with antibodies specific to the C-terminal region of nebulin indicated that the mutations may cause protein truncation possibly associated with loss of fiber-type diversity, which may be relevant to disease pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy, <a href="#3" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. <strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong> Hum. Genet. 115: 185-190, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221447</a>] [<a href="https://doi.org/10.1007/s00439-004-1140-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15221447">Anderson et al. (2004)</a> identified a 2,502-bp deletion in the NEB gene (ex55del; <a href="#0007">161650.0007</a>). Screening for this mutation in a random sample of 4,090 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 108. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 patients from 4 unrelated Finnish families, 2 of whom were consanguineous, with NEM2 manifest as distal myopathy with onset in childhood or adulthood, <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> identified homozygous missense mutations in the NEB (T5681P, <a href="#0008">161650.0008</a> and S4665I, <a href="#0009">161650.0009</a>). The mutations segregated with the disorder in the families from whom DNA was available. Functional studies of the mutation were not performed, but <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> noted that both missense mutations had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more severe typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17525139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Arthrogryposis Multiplex Congenita 6</em></strong></p><p>
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In affected infants from 5 unrelated families with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#22" class="mim-tip-reference" title="Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K. <strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong> Neuromusc. Disord. 12: 674-679, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12207937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12207937</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00065-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12207937">Wallgren-Pettersson et al. (2002)</a> identified mutations in the NEB gene. All the mutations were predicted to result in premature termination and a loss of function with absence of the C-terminus of the protein. One of the families of French descent (family 1) had previously been reported by <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> (family 3) as having NEM2, but <a href="#22" class="mim-tip-reference" title="Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K. <strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong> Neuromusc. Disord. 12: 674-679, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12207937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12207937</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00065-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12207937">Wallgren-Pettersson et al. (2002)</a> stated that the phenotype was more consistent with AMC6 (see <a href="#0003">161650.0003</a> and <a href="#0004">161650.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10051637+12207937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 brothers with AMC6, <a href="#7" class="mim-tip-reference" title="Lawlor, M. W., Ottenheijm, C. A., Lehtokari, V.-L., Cho, K., Pelin, K., Wallgren-Pettersson, C., Granzier, H., Beggs, A. H. <strong>Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy.</strong> Skeletal Muscle 1: 23, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21798101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21798101</a>] [<a href="https://doi.org/10.1186/2044-5040-1-23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21798101">Lawlor et al. (2011)</a> identified compound heterozygous loss-of-function mutations in the NEB gene (<a href="#0012">161650.0012</a> and <a href="#0013">161650.0013</a>). The mutations, which were found by deep sequencing of the NEB gene, segregated with the disorder in the family. Western blot analysis of skeletal muscle tissue from 1 of the patients showed significantly decreased nebulin levels compared to controls. In vitro mechanical studies of patient-derived myofibers showed that they had decreased tension and impaired force generation, which the authors suggested could be explained by altered cross-bridge cycling kinetics. The severe phenotype may correlate with the significant decrease in nebulin protein levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21798101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Yonath, H., Reznik-Wolf, H., Berkenstadt, M., Eisenberg-Barzilai, S., Lehtokari, V.-L., Wallgren-Pettersson, C., Mehta, L., Achiron, R., Gilboa, Y., Polak-Charcon, S., Winder, T., Frydman, M., Pras, E. <strong>Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy.</strong> Prenatal Diag. 32: 70-74, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22367672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22367672</a>] [<a href="https://doi.org/10.1002/pd.2905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22367672">Yonath et al. (2012)</a> reported 4 unrelated pregnancies with abnormal prenatal ultrasound findings in fetuses with AMC6. In each family, 1 or both of the parents was of Ashkenazi Jewish descent, and the common exon 55 deletion in the NEB gene (<a href="#0007">161650.0007</a>) was found in the heterozygous state in the patients and in unaffected parents. A second pathogenic NEB mutation was found in 3 of the patients; a second mutation could not be identified in 1 of the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22367672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In twin male fetuses, conceived of consanguineous parents, with AMC6, <a href="#21" class="mim-tip-reference" title="Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., Haliloglu, G., Talim, B., Akcoren, Z., Kariminejad, A., Cairns, A., Clarke, N. F., and 14 others. <strong>Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.</strong> Orphanet J. Rare Dis. 10: 148, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26578207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26578207</a>] [<a href="https://doi.org/10.1186/s13023-015-0364-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26578207">Todd et al. (2015)</a> identified a homozygous nonsense mutation in the NEB gene (R974X; <a href="#0010">161650.0010</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Postmortem examination showed joint contractures, talipes, multiple pterygia, hypertelorism, and cystic hygromas. A previous fetus was therapeutically aborted due to hydrops fetalis at 19 weeks' gestation. Functional studies of the variant and studies of patient cells were not performed. In affected patients from 3 additional families diagnosed with fetal akinesia, a heterozygous splice site, frameshift, or truncating mutation in the NEB gene was found. A second pathogenic mutation was not found in these patients, but there was evidence for autosomal recessive inheritance, suggesting that the affected fetuses carried a second pathogenic variant. <a href="#21" class="mim-tip-reference" title="Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., Haliloglu, G., Talim, B., Akcoren, Z., Kariminejad, A., Cairns, A., Clarke, N. F., and 14 others. <strong>Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.</strong> Orphanet J. Rare Dis. 10: 148, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26578207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26578207</a>] [<a href="https://doi.org/10.1186/s13023-015-0364-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26578207">Todd et al. (2015)</a> noted the difficulty in screening the nebulin gene for mutations because of its large size and because next-generation sequencing data may not accurately identify pathogenic small copy number variations. These 4 families were ascertained from a cohort of 38 families with severe neuromuscular disease apparent before or at birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26578207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sib fetuses with AMC6, <a href="#2" class="mim-tip-reference" title="Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., Saunders, C. <strong>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</strong> Am. J. Med. Genet. 176A: 359-367, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29274205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29274205</a>] [<a href="https://doi.org/10.1002/ajmg.a.38577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29274205">Ahmed et al. (2018)</a> identified compound heterozygous nonsense mutations in the NEB gene (Y6262X, <a href="#0014">161650.0014</a> and Y6327X, <a href="#0015">161650.0015</a>). The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family had previously been reported by <a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a>. Functional studies of the variants and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29274205+25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male fetus, conceived of consanguineous Lebanese parents, with AMC6, <a href="#17" class="mim-tip-reference" title="Rocha, M. L., Dittmayer, C., Uruha, A., Korinth, D., Chaoui, R., Schlembach, D., Rossi, R., Pelin, K., Suk, E. K., Schmid, S., Goebel, H. H., Schuelke, M., Stenzel, W., Englert, B. <strong>A novel mutation in NEB causing foetal nemaline myopathy with arthrogryposis during early gestation.</strong> Neuromusc. Disord. 31: 239-245, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33376055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33376055</a>] [<a href="https://doi.org/10.1016/j.nmd.2020.11.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33376055">Rocha et al. (2021)</a> identified a homozygous splice site mutation in the NEB gene (<a href="#0016">161650.0016</a>). The mutation, which was found by next-generation sequencing, segregated in the family, with both parents heterozygous carriers. The mutation was not present in the gnomAD database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33376055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K. <strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong> Europ. J. Hum. Genet. 12: 744-751, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266303</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266303">Donner et al. (2004)</a> found that alternatively spliced exons 143 and 144 of the NEB gene give rise to 2 different transcripts that vary between muscle types and between muscles of different developmental stages. Alternatively spliced exons 166 to 177 express at least 20 different transcripts in adult human tibialis anterior muscle alone. <a href="#4" class="mim-tip-reference" title="Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K. <strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong> Europ. J. Hum. Genet. 12: 744-751, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266303</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266303">Donner et al. (2004)</a> suggested that the extensive alternative splicing of NEB may explain why nemaline myopathy patients with homozygous truncating mutations show expression of the C terminus of the protein. The use of alternative transcripts may also explain why severe phenotypes are rare among patients with 2 truncating mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 denaturing high-performance liquid chromatography (DHPLC), <a href="#10" class="mim-tip-reference" title="Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C. <strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Hum. Mutat. 27: 946-956, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917880</a>] [<a href="https://doi.org/10.1002/humu.20370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16917880">Lehtokari et al. (2006)</a> identified 45 novel mutations in the NEB gene in affected members of 44 unrelated families with nemaline myopathy. Mutations were identified in patients representing all clinical categories of disease severity. The majority (55%) of mutations were frameshift or nonsense mutations resulting in premature termination of the protein. Mutations were distributed throughout the gene, with no obvious hotspots. <a href="#10" class="mim-tip-reference" title="Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C. <strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Hum. Mutat. 27: 946-956, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917880</a>] [<a href="https://doi.org/10.1002/humu.20370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16917880">Lehtokari et al. (2006)</a> concluded that mutations in the NEB gene are the most common cause of nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, <a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a> found that the most common types of mutations were splice-site mutations (34%), followed by frameshift (32%), nonsense (23%), and finally missense (7%). The vast majority of patients had compound heterozygous mutations. There were no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#25" class="mim-tip-reference" title="Witt, C. C., Burkart, C., Labeit, D., McNabb, M., Wu, Y., Granzier, H., Labeit, S. <strong>Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo.</strong> EMBO J. 25: 3843-3855, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16902413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16902413</a>] [<a href="https://doi.org/10.1038/sj.emboj.7601242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16902413">Witt et al. (2006)</a> found that Neb -/- mice showed growth retardation 1 day after birth and did not survive beyond week 3. All Neb -/- mice developed a stiff gait and kyphosis, but they could walk up to week 3. Between days 10 and 20, Neb -/- mice developed progressive muscle weakness. Microarray analysis identified 40 differentially expressed genes in Neb -/- mice, and RT-PCR analysis confirmed upregulation of sarcolipin (SLN; <a href="/entry/602203">602203</a>), S100a4 (<a href="/entry/114210">114210</a>), S100a9 (<a href="/entry/123886">123886</a>), desmoplakin (DSP; <a href="/entry/125647">125647</a>), and Ankrd2 (<a href="/entry/610734">610734</a>). Characterization of skeletal myofibrils showed that absence of Neb caused loss of thin filament length control and pointed end capping in skeletal muscle tissues. However, the genes dysregulated in Neb -/- skeletal muscle were not differentially expressed in Neb -/- myocardium, indicating that nebulin is not a ruler molecule for thin filaments in myocardium. Neb was required to fine-tune calcium-dependent contractility, and consequently, loss of Neb resulted in abnormal calcium sensitivity and Z-disk morphology in skeletal muscle. Furthermore, Neb played important roles in maintaining physiologic Z-disk width and protein composition in skeletal tissues, and its absence led to formation of nemaline bodies and wide Z-disks in mice, recapitulating the phenotype of human nemaline myopathy. Further analysis demonstrated that the C-terminal region of Neb interacted with CapZ (see <a href="/entry/601580">601580</a>) and titin (TTN; <a href="/entry/188840">188840</a>), thereby linking these 2 ruler molecules implied in Z-disk width specification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16902413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1057515573 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057515573;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=rs1057515573" 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=rs1057515573" 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=RCV000015090 OR RCV005016266" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015090, RCV005016266" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015090...</a>
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<p>In 2 affected sibs from a British family (family 1) with nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>), <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> identified a heterozygous 1-bp (G) deletion in exon 165 of the NEB gene, predicted to cause a truncation of the protein at the repeat domain M166. Based on the haplotypes in this family, the authors suspected that the children's maternal allele harbored an as yet unknown NEB mutation. The unaffected father also carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1057515574 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057515574;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=rs1057515574" 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=rs1057515574" 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=RCV000015091" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015091" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015091</a>
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<p>In a Finnish child (family 2) with nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>), <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> identified a 4-bp (GTTT) duplication/insertion in exon 172 of the NEB gene encoding part of the repeat domains M172 and M173. The child had inherited the mutation from her unaffected mother. The duplication was predicted to cause a frameshift leading to a stop codon in the beginning of exon 173, and truncation of the protein from domain M173. Haplotype analysis suggested that the child had inherited a different, unidentified, mutation from her unaffected father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</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">rs1553603400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553603400;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=rs1553603400" 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=rs1553603400" 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=RCV000673087 OR RCV002280821" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000673087, RCV002280821" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000673087...</a>
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<p>In 2 sibs, born of unrelated French parents (family 3) with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> identified compound heterozygous mutations in the NEB gene: a 2-bp (AG) deletion in exon 172 and a 2-bp (GA) deletion in exon 181 (<a href="#0004">161650.0004</a>). The first mutation would lead to a stop codon in the beginning of exon 173 and a truncation of the protein from domain M173. The second mutation would lead to a stop codon in exon 181 and truncation of the protein from domain M182. Exon 181 is within the alternatively spliced region of NEB, and the maternal mutation may therefore affect only some of the nebulin isoforms. Each unaffected parent was heterozygous for 1 of the mutations, confirming segregation and autosomal recessive inheritance. Although <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> reported that these children had nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>), <a href="#22" class="mim-tip-reference" title="Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K. <strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong> Neuromusc. Disord. 12: 674-679, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12207937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12207937</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00065-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12207937">Wallgren-Pettersson et al. (2002)</a> stated that, on reexamination, these patients (family 1 in their report) had the severe form of the disorder with arthrogryposis and no spontaneous movements; both infants died in the first weeks of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10051637+12207937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1559154278 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559154278;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=rs1559154278" 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=rs1559154278" 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=RCV000015093" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015093" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015093</a>
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<p>For discussion of the 2-bp (GA) deletion in exon 181 of the NEB gene that was found in compound heterozygous state in 2 infant sibs with arthrogryposis multiple congenita-6 (AMC6; <a href="/entry/619334">619334</a>) by <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a>, see <a href="#0003">161650.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913662;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913662?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913662" 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=rs121913662" 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=RCV000015094" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015094" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015094</a>
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<p><a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> found that a British child with autosomal recessive nemaline myopathy (NEM2; <a href="/entry/256030">256030</a>), whose parents were consanguineous (family 5), had a homozygous G-to-T transversion in exon 185 of the NEB gene, resulting in a glu6636-to-ter (E6636X) substitution. The mutation was predicted to result in the loss of the last 134 amino acids of the protein, from the beginning of the serine-rich domain of the C-terminal region of nebulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 the only affected child with nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>) of a consanguineous German family of Turkish descent (family 4), <a href="#15" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. <strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong> Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051637">Pelin et al. (1999)</a> found homozygosity for a G-to-C transversion in the last codon of exon 163 of the NEB gene. The mutation interfered with the 5-prime consensus splice site of intron 163 and was predicted to cause an in-frame skipping of exon 163 or partial retention of intron 163, because of activation of a cryptic splice site 100-bp downstream in intron 163. The latter mRNA had a stop codon 36-bp downstream of exon 163. The abnormally spliced mRNA was seen as 2 distinct RT-PCR products different from the control mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs80358246 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358246;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=rs80358246" 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=rs80358246" 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=RCV000015096 OR RCV001449896" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015096, RCV001449896" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015096...</a>
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<p><strong><em>Nemaline Myopathy 2</em></strong></p><p>
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In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy (NEM2; <a href="/entry/256030">256030</a>), <a href="#3" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. <strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong> Hum. Genet. 115: 185-190, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221447</a>] [<a href="https://doi.org/10.1007/s00439-004-1140-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15221447">Anderson et al. (2004)</a> identified a homozygosity for a 2,502-bp deletion completely encompassing exon 55 and parts of introns 54 and 55 of the NEB gene, predicted to result in a transcript encoding 35 fewer amino acids. Screening for this mutation in a random sample of 4,090 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 108. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C. <strong>The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.</strong> Neuromusc. Disord. 19: 179-181, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19232495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19232495</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19232495">Lehtokari et al. (2009)</a> identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by <a href="#3" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. <strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong> Hum. Genet. 115: 185-190, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221447</a>] [<a href="https://doi.org/10.1007/s00439-004-1140-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15221447">Anderson et al. (2004)</a>. Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15221447+19232495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H. <strong>Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.</strong> Hum. Molec. Genet. 18: 2359-2369, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19346529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19346529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[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/ddp168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19346529">Ottenheijm et al. (2009)</a> studied the muscular phenotype of nemaline myopathy patients with NEB exon 55 deletion (NM-NEB). SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. <a href="#14" class="mim-tip-reference" title="Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H. <strong>Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.</strong> Hum. Molec. Genet. 18: 2359-2369, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19346529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19346529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[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/ddp168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19346529">Ottenheijm et al. (2009)</a> hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19346529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Arthrogryposis Multiplex Congenita 6</em></strong></p><p>
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<a href="#26" class="mim-tip-reference" title="Yonath, H., Reznik-Wolf, H., Berkenstadt, M., Eisenberg-Barzilai, S., Lehtokari, V.-L., Wallgren-Pettersson, C., Mehta, L., Achiron, R., Gilboa, Y., Polak-Charcon, S., Winder, T., Frydman, M., Pras, E. <strong>Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy.</strong> Prenatal Diag. 32: 70-74, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22367672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22367672</a>] [<a href="https://doi.org/10.1002/pd.2905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22367672">Yonath et al. (2012)</a> reported 4 unrelated pregnancies with abnormal prenatal ultrasound findings in fetuses with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>). In each family, 1 or both of the parents was of Ashkenazi Jewish descent, and the common exon 55 deletion in the NEB gene was found in the heterozygous state in the patients and in unaffected parents. A second pathogenic NEB mutation was found in 3 of the patients; a second mutation could not be identified in 1 of the patients. Prenatal ultrasound showed polyhydramnios, decreased fetal movements, clubfoot, and clenched hands. All patients showed severe hypotonia after birth, and all died within the first months of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22367672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Feingold-Zadok, M., Chitayat, D., Chong, K., Injeyan, M., Shannon, P., Chapmann, D., Maymon, R., Pillar, N., Reish, O. <strong>Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita.</strong> Prenatal Diag. 37: 144-150, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27933661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27933661</a>] [<a href="https://doi.org/10.1002/pd.4977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27933661">Feingold-Zadok et al. (2017)</a> identified this mutation in 2 fetal sibs with AMC6 from an Ashkenazi Jewish family (family 1), in compound heterozygosity with a splice site mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27933661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs761232641 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs761232641;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs761232641?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs761232641" 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=rs761232641" 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=RCV000611555 OR RCV004732973" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000611555, RCV004732973" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000611555...</a>
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<p>In 5 patients from 2 unrelated Finnish families, one of which was consanguineous, with nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>) manifest as distal myopathy with onset in childhood or adulthood, <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> identified a homozygous mutation (g.207181A-C, NT_005403) in exon 151 of the NEB gene, resulting in a thr5681-to-pro (T5681P) substitution. The mutation segregated with this disorder in the families and was not found in 300 Finnish control chromosomes. Functional studies of the mutation were not performed, but <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> noted that T5681P had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. <a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a> referred to this mutation as THR7417PRO (T7417P), resulting from a c.22249A-C transversion (c.22249A-C, NM_001271208.1), and noted that <a href="#12" class="mim-tip-reference" title="Marttila, M., Hanif, M., Lemola, E., Nowak, K. J., Laitila, J., Gronholm, M., Wallgren-Pettersson, C., Pelin, K. <strong>Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations.</strong> Skeletal Muscle 4: 15, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110572</a>] [<a href="https://doi.org/10.1186/2044-5040-4-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25110572">Marttila et al. (2014)</a> found that the variant reduces the affinity of nebulin for tropomyosin. <a href="#12" class="mim-tip-reference" title="Marttila, M., Hanif, M., Lemola, E., Nowak, K. J., Laitila, J., Gronholm, M., Wallgren-Pettersson, C., Pelin, K. <strong>Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations.</strong> Skeletal Muscle 4: 15, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110572</a>] [<a href="https://doi.org/10.1186/2044-5040-4-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25110572">Marttila et al. (2014)</a> referred to the mutation as THR7382PRO (c.22144A-C, NM_001164507.1). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17525139+25110572+25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs191579691 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs191579691;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs191579691?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs191579691" 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=rs191579691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated Finnish women, one of which was born of consanguineous parents, with nemaline myopathy-2 (NEM2; <a href="/entry/256030">256030</a>) manifest as distal myopathy with onset in childhood or adulthood, <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> identified a homozygous mutation in exon 122 (g.171944G-T, NT_005403) of the NEB gene, resulting in a ser4665-to-ile (S4665I) substitution. The mutation segregated with the disorder in 1 of the families; DNA was not available from other members of the second family. The mutation was not found in 188 Finnish control chromosomes nor in 90 additional control chromosomes from the same geographic region. Functional studies of the variant were not performed, but <a href="#23" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. <strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong> Brain 130: 1465-1476, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>] [<a href="https://doi.org/10.1093/brain/awm094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> noted that S4665I had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. <a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a> referred to this mutation as SER6366ILE (S6366I), resulting from a c.19097G-T transversion (c.19097G-T, NM_001271208.1) and noted that <a href="#12" class="mim-tip-reference" title="Marttila, M., Hanif, M., Lemola, E., Nowak, K. J., Laitila, J., Gronholm, M., Wallgren-Pettersson, C., Pelin, K. <strong>Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations.</strong> Skeletal Muscle 4: 15, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110572</a>] [<a href="https://doi.org/10.1186/2044-5040-4-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25110572">Marttila et al. (2014)</a> found that the variant increases nebulin-actin affinity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17525139+25110572+25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a> reported another Finnish patient with distal nemaline myopathy who was compound heterozygous for the S6366I mutation and a splice site variant in the NEB gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1553548666 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553548666;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=rs1553548666" 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=rs1553548666" 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=RCV000530974 OR RCV001449887 OR RCV004017670" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000530974, RCV001449887, RCV004017670" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000530974...</a>
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<p>In twin male fetuses, conceived of consanguineous parents (family 9), with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>) presenting as fetal akinesia with lethal multiple pterygia syndrome, <a href="#21" class="mim-tip-reference" title="Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., Haliloglu, G., Talim, B., Akcoren, Z., Kariminejad, A., Cairns, A., Clarke, N. F., and 14 others. <strong>Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.</strong> Orphanet J. Rare Dis. 10: 148, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26578207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26578207</a>] [<a href="https://doi.org/10.1186/s13023-015-0364-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26578207">Todd et al. (2015)</a> identified a homozygous c.2920C-T transition (c.2920C-T, NM_001164508) in exon 29 of the NEB gene, predicted to result in an arg974-to-ter (R974X) substitution. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the ExAC database. Postmortem examination showed joint contractures, talipes, multiple pterygia, hypertelorism, and cystic hygromas. A previous fetus was therapeutically aborted due to hydrops fetalis at 19 weeks' gestation. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26578207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 male fetus, conceived of consanguineous Egyptian parents, with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#1" class="mim-tip-reference" title="Abdalla, E., Ravenscroft, G., Zayed, L., Beecroft, S. J., Laing, N. G. <strong>Lethal multiple pterygium syndrome: a severe phenotype associated with a novel mutation in the nebulin gene.</strong> Neuromusc. Disord. 27: 537-541, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28336317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28336317</a>] [<a href="https://doi.org/10.1016/j.nmd.2017.01.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28336317">Abdalla et al. (2017)</a> identified a homozygous G-to-T transversion in intron 74 of the NEB gene (c.10872+1G-T, ENST00000427231.2). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to disrupt an essential splice site. A similarly affected fetus from this family was therapeutically aborted at 20 weeks' gestation; DNA was not available from that patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28336317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs398124167 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124167;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs398124167?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs398124167" 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=rs398124167" 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=RCV000174538 OR RCV000790650 OR RCV001174709 OR RCV001449897 OR RCV002477236" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000174538, RCV000790650, RCV001174709, RCV001449897, RCV002477236" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000174538...</a>
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<p>In 2 brothers with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#7" class="mim-tip-reference" title="Lawlor, M. W., Ottenheijm, C. A., Lehtokari, V.-L., Cho, K., Pelin, K., Wallgren-Pettersson, C., Granzier, H., Beggs, A. H. <strong>Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy.</strong> Skeletal Muscle 1: 23, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21798101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21798101</a>] [<a href="https://doi.org/10.1186/2044-5040-1-23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21798101">Lawlor et al. (2011)</a> identified compound heterozygous loss-of-function mutations in the NEB gene: a G-to-T transversion in intron 13 (c.1152+1G-T, NG_009382.1), predicted to result in a splice site alteration, and a 2-bp deletion in exon 81 (c.11318_11319delAG; <a href="#0013">161650.0013</a>), predicted to result in a frameshift and premature termination (Lys3774ArgfsTer10). The mutations, which were found by deep sequencing of the NEB gene, segregated with the disorder in the family. Neither mutation was present in 236 control chromosomes. Western blot analysis of skeletal muscle from 1 of the patients showed significantly decreased nebulin levels compared to controls. In vitro mechanical studies of patient-derived myofibers showed that they had decreased tension and impaired force generation, which the authors suggested could be explained by altered cross-bridge cycling kinetics. The severe phenotype may correlate with the significant decrease in nebulin protein levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21798101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</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">rs2153972327 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2153972327;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=rs2153972327" 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=rs2153972327" 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=RCV001449898" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001449898" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001449898</a>
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<p>For discussion of the 2-bp deletion in exon 81 of the NEB gene (c.11318_11319delAG, NG_009382.1), predicted to result in a frameshift and premature termination (Lys3774ArgfsTer10), that was found in compound heterozygous state in 2 brothers with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>) by <a href="#7" class="mim-tip-reference" title="Lawlor, M. W., Ottenheijm, C. A., Lehtokari, V.-L., Cho, K., Pelin, K., Wallgren-Pettersson, C., Granzier, H., Beggs, A. H. <strong>Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy.</strong> Skeletal Muscle 1: 23, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21798101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21798101</a>] [<a href="https://doi.org/10.1186/2044-5040-1-23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21798101">Lawlor et al. (2011)</a>, see <a href="#0012">161650.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21798101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<span class="mim-font">
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<strong>.0014 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
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NEB, TYR6262TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs374874999 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs374874999;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs374874999?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs374874999" 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=rs374874999" 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=RCV001449899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001449899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001449899</a>
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<p>In 2 sib fetuses with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#2" class="mim-tip-reference" title="Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., Saunders, C. <strong>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</strong> Am. J. Med. Genet. 176A: 359-367, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29274205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29274205</a>] [<a href="https://doi.org/10.1002/ajmg.a.38577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29274205">Ahmed et al. (2018)</a> identified compound heterozygous nonsense mutations in the NEB gene: a c.18786C-G transversion (c.18786C-G, NM_001271208.1), resulting in a tyr6262-to-ter (Y6262X) substitution, and a c.18981C-G transversion, resulting in a tyr6327-to-ter (Y6327X; <a href="#0015">161650.0015</a>) substitution. The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family had previously been reported by <a href="#9" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. <strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong> Hum. Mutat. 35: 1418-1426, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>] [<a href="https://doi.org/10.1002/humu.22693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25205138">Lehtokari et al. (2014)</a>. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29274205+25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0015" class="mim-anchor"></a>
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<strong>.0015 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
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NEB, TYR6327TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs761964375 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs761964375;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs761964375?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs761964375" 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=rs761964375" 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=RCV000673447 OR RCV001449900" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000673447, RCV001449900" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000673447...</a>
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<p>For discussion of the c.18981C-G transversion (c.18981C-G, NM_001271208.1) in the NEB gene, resulting in a tyr6327-to-ter (Y6327X) substitution, that was found in compound heterozygous state in 2 sib fetuses with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>) by <a href="#2" class="mim-tip-reference" title="Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., Saunders, C. <strong>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</strong> Am. J. Med. Genet. 176A: 359-367, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29274205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29274205</a>] [<a href="https://doi.org/10.1002/ajmg.a.38577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29274205">Ahmed et al. (2018)</a>, see <a href="#0014">161650.0014</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29274205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0016" class="mim-anchor"></a>
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<strong>.0016 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
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NEB, IVS122AS, G-T, -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">rs2153702473 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2153702473;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=rs2153702473" 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=rs2153702473" 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=RCV001449901" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001449901" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001449901</a>
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<p>In a male fetus, conceived on consanguineous Lebanese parents, with arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), <a href="#17" class="mim-tip-reference" title="Rocha, M. L., Dittmayer, C., Uruha, A., Korinth, D., Chaoui, R., Schlembach, D., Rossi, R., Pelin, K., Suk, E. K., Schmid, S., Goebel, H. H., Schuelke, M., Stenzel, W., Englert, B. <strong>A novel mutation in NEB causing foetal nemaline myopathy with arthrogryposis during early gestation.</strong> Neuromusc. Disord. 31: 239-245, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33376055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33376055</a>] [<a href="https://doi.org/10.1016/j.nmd.2020.11.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33376055">Rocha et al. (2021)</a> identified a homozygous G-to-T transition in intron 22 (c.19102-1G-T, NM_001164508) of the NEB gene, predicted to result in a splicing defect. The mutation, which was found by next-generation sequencing, segregated in the family, with both parents heterozygous carriers. The mutation was not present in the gnomAD database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33376055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<li>
|
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<a id="1" class="mim-anchor"></a>
|
|
<a id="Abdalla2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abdalla, E., Ravenscroft, G., Zayed, L., Beecroft, S. J., Laing, N. G.
|
|
<strong>Lethal multiple pterygium syndrome: a severe phenotype associated with a novel mutation in the nebulin gene.</strong>
|
|
Neuromusc. Disord. 27: 537-541, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28336317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28336317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28336317" 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.2017.01.013" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Ahmed2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., Saunders, C.
|
|
<strong>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</strong>
|
|
Am. J. Med. Genet. 176A: 359-367, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29274205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29274205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29274205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1002/ajmg.a.38577" target="_blank">Full Text</a>]
|
|
|
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Anderson2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y.
|
|
<strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong>
|
|
Hum. Genet. 115: 185-190, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1007/s00439-004-1140-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Donner2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K.
|
|
<strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong>
|
|
Europ. J. Hum. Genet. 12: 744-751, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266303" 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/sj.ejhg.5201242" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Feingold-Zadok2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Feingold-Zadok, M., Chitayat, D., Chong, K., Injeyan, M., Shannon, P., Chapmann, D., Maymon, R., Pillar, N., Reish, O.
|
|
<strong>Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita.</strong>
|
|
Prenatal Diag. 37: 144-150, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27933661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27933661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27933661" 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/pd.4977" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Labeit1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Labeit, S., Kolmerer, B.
|
|
<strong>The complete primary structure of human nebulin and its correlation to muscle structure.</strong>
|
|
J. Molec. Biol. 248: 308-315, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7739042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7739042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7739042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-2836(95)80052-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Lawlor2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lawlor, M. W., Ottenheijm, C. A., Lehtokari, V.-L., Cho, K., Pelin, K., Wallgren-Pettersson, C., Granzier, H., Beggs, A. H.
|
|
<strong>Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy.</strong>
|
|
Skeletal Muscle 1: 23, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21798101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21798101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21798101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1186/2044-5040-1-23" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Lehtokari2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C.
|
|
<strong>The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.</strong>
|
|
Neuromusc. Disord. 19: 179-181, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19232495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19232495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19232495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2008.12.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Lehtokari2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C.
|
|
<strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong>
|
|
Hum. Mutat. 35: 1418-1426, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" 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/humu.22693" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Lehtokari2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C.
|
|
<strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
|
|
Hum. Mutat. 27: 946-956, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917880</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20370" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Limongi1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Limongi, M. Z., Pelliccia, F., Rocchi, A.
|
|
<strong>Assignment of the human nebulin gene (NEB) to chromosome band 2q24.2 and the alpha-1 (III) collagen gene (COL3A1) to chromosome band 2q32.2 by in situ hybridization: the FRA2G common fragile site lies between the two genes in the 2q31 band.</strong>
|
|
Cytogenet. Cell Genet. 77: 259-260, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9284930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9284930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9284930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000134590" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Marttila2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marttila, M., Hanif, M., Lemola, E., Nowak, K. J., Laitila, J., Gronholm, M., Wallgren-Pettersson, C., Pelin, K.
|
|
<strong>Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations.</strong>
|
|
Skeletal Muscle 4: 15, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110572</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25110572" 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/10.1186/2044-5040-4-15" target="_blank">Full Text</a>]
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|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
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<a id="McElhinny2005" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
McElhinny, A. S., Schwach, C., Valichnac, M., Mount-Patrick, S., Gregorio, C. C.
|
|
<strong>Nebulin regulates the assembly and lengths of the thin filaments in striated muscle.</strong>
|
|
J. Cell Biol. 170: 947-957, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16157704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16157704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16157704[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=16157704" 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/10.1083/jcb.200502158" target="_blank">Full Text</a>]
|
|
|
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|
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Ottenheijm2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H.
|
|
<strong>Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.</strong>
|
|
Hum. Molec. Genet. 18: 2359-2369, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19346529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19346529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[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=19346529" 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/ddp168" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Pelin1999" class="mim-anchor"></a>
|
|
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|
|
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|
|
Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
|
|
<strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[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=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
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|
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<a id="Pelin1997" class="mim-anchor"></a>
|
|
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|
|
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|
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Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
|
|
<strong>Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.</strong>
|
|
Europ. J. Hum. Genet. 5: 229-234, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9359044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9359044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9359044" 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 id="Rocha2021" class="mim-anchor"></a>
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<div class="">
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Rocha, M. L., Dittmayer, C., Uruha, A., Korinth, D., Chaoui, R., Schlembach, D., Rossi, R., Pelin, K., Suk, E. K., Schmid, S., Goebel, H. H., Schuelke, M., Stenzel, W., Englert, B.
|
|
<strong>A novel mutation in NEB causing foetal nemaline myopathy with arthrogryposis during early gestation.</strong>
|
|
Neuromusc. Disord. 31: 239-245, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33376055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33376055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33376055" 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.2020.11.014" target="_blank">Full Text</a>]
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<a id="Schurr1991" class="mim-anchor"></a>
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|
<div class="">
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|
Schurr, E., Skamene, E., Gros, P.
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<strong>Mapping of the gene coding for the muscle protein nebulin (Neb) to the proximal region of mouse chromosome 2.</strong>
|
|
Cytogenet. Cell Genet. 57: 214-216, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1683831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1683831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1683831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000133150" target="_blank">Full Text</a>]
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|
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|
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<a id="Stedman1988" class="mim-anchor"></a>
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Stedman, H., Browning, K., Oliver, N., Oronzi-Scott, M., Fischbeck, K., Sarkar, S., Sylvester, J., Schmickel, R., Wang, K.
|
|
<strong>Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2.</strong>
|
|
Genomics 2: 1-7, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2838409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2838409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2838409" 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/10.1016/0888-7543(88)90102-4" target="_blank">Full Text</a>]
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|
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<a id="Takano2010" class="mim-anchor"></a>
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Takano, K., Watanabe-Takano, H., Suetsugu, S., Kurita, S., Tsujita, K., Kimura, S., Karatsu, T., Takenawa, T., Endo, T.
|
|
<strong>Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.</strong>
|
|
Science 330: 1536-1540, 2010.
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21148390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21148390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21148390" 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/10.1126/science.1197767" target="_blank">Full Text</a>]
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<a id="Todd2015" class="mim-anchor"></a>
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Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., Haliloglu, G., Talim, B., Akcoren, Z., Kariminejad, A., Cairns, A., Clarke, N. F., and 14 others.
|
|
<strong>Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.</strong>
|
|
Orphanet J. Rare Dis. 10: 148, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26578207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26578207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26578207" 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/10.1186/s13023-015-0364-0" target="_blank">Full Text</a>]
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Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K.
|
|
<strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong>
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|
Neuromusc. Disord. 12: 674-679, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12207937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12207937</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12207937" 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/s0960-8966(02)00065-2" target="_blank">Full Text</a>]
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Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B.
|
|
<strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong>
|
|
Brain 130: 1465-1476, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17525139" 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/brain/awm094" target="_blank">Full Text</a>]
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Wang, K., Knipfer, M., Huang, Q.-Q., van Heerden, A., Hsu, L. C.-L., Gutierrez, G., Quian, X.-L., Stedman, H.
|
|
<strong>Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture: sequence motifs and affinity profiles of tandem repeats and terminal SH3.</strong>
|
|
J. Biol. Chem. 271: 4304-4314, 1996.
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8626778" 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.271.8.4304" target="_blank">Full Text</a>]
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Witt, C. C., Burkart, C., Labeit, D., McNabb, M., Wu, Y., Granzier, H., Labeit, S.
|
|
<strong>Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo.</strong>
|
|
EMBO J. 25: 3843-3855, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16902413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16902413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16902413" 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/sj.emboj.7601242" target="_blank">Full Text</a>]
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Yonath, H., Reznik-Wolf, H., Berkenstadt, M., Eisenberg-Barzilai, S., Lehtokari, V.-L., Wallgren-Pettersson, C., Mehta, L., Achiron, R., Gilboa, Y., Polak-Charcon, S., Winder, T., Frydman, M., Pras, E.
|
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<strong>Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy.</strong>
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Prenatal Diag. 32: 70-74, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22367672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22367672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22367672" 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/pd.2905" target="_blank">Full Text</a>]
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Zeviani, M., Darras, B. T., Rizzuto, R., Salviati, G., Betto, R., Bonilla, E., Miranda, A. F., Du, J., Samitt, C., Dickson, G., Walsh, F. S., DiMauro, S., Francke, U., Schon, E. A.
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<strong>Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32.</strong>
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Genomics 2: 249-256, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3397062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3397062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3397062" 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/10.1016/0888-7543(88)90009-2" target="_blank">Full Text</a>]
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Bao Lige - updated : 09/01/2021
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Cassandra L. Kniffin - updated : 05/21/2021<br>Cassandra L. Kniffin - updated : 03/27/2018<br>Ada Hamosh - updated : 1/19/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 10/16/2009<br>Patricia A. Hartz - updated : 10/19/2006<br>Cassandra L. Kniffin - updated : 9/19/2006<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Cassandra L. Kniffin - updated : 4/4/2005<br>Patricia A. Hartz - updated : 10/19/2004<br>Victor A. McKusick - updated : 4/28/1999<br>Victor A. McKusick - updated : 10/30/1997<br>Victor A. McKusick - updated : 10/20/1997<br>Alan F. Scott - updated : 5/20/1996
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 12/4/1987
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carol : 05/28/2021<br>alopez : 05/27/2021<br>alopez : 05/27/2021<br>ckniffin : 05/21/2021<br>carol : 08/16/2019<br>carol : 04/03/2018<br>alopez : 04/02/2018<br>ckniffin : 03/27/2018<br>carol : 08/18/2016<br>carol : 09/17/2013<br>alopez : 1/19/2011<br>alopez : 1/19/2011<br>terry : 1/19/2011<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>wwang : 11/12/2009<br>ckniffin : 10/16/2009<br>terry : 7/3/2008<br>carol : 10/25/2006<br>terry : 10/19/2006<br>wwang : 9/21/2006<br>ckniffin : 9/19/2006<br>wwang : 4/27/2005<br>wwang : 4/19/2005<br>terry : 4/18/2005<br>ckniffin : 4/12/2005<br>carol : 4/7/2005<br>ckniffin : 4/4/2005<br>alopez : 10/19/2004<br>alopez : 10/19/2004<br>terry : 4/28/1999<br>terry : 4/28/1999<br>terry : 4/28/1999<br>jenny : 11/5/1997<br>terry : 10/30/1997<br>mark : 10/22/1997<br>terry : 10/20/1997<br>mark : 6/25/1996<br>mark : 5/20/1996<br>terry : 5/20/1996<br>carol : 11/12/1993<br>supermim : 3/16/1992<br>carol : 2/5/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>root : 7/8/1988
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<strong>*</strong> 161650
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NEBULIN; NEB
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NEB</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>
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<em>
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Cytogenetic location: 2q23.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:151,485,339-151,734,476 </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="2">
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<span class="mim-font">
|
|
2q23.3
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|
</span>
|
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</td>
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|
|
|
|
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<td>
|
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<span class="mim-font">
|
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Arthrogryposis multiplex congenita 6
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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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619334
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</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
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<td>
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<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Nemaline myopathy 2, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256030
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</span>
|
|
</td>
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
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<td>
|
|
<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>
|
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
|
<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>Nebulin is a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein and its size varies from 600 to 800 kD in a manner that is tissue-, species-, and developmental stage-specific (Stedman et al., 1988). A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs (Pelin et al., 1999). </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>Using polyclonal nebulin antisera to screen a cDNA expression library, Stedman et al. (1988) isolated 2 separate human fetal muscle cDNA clones. Both cDNAs detected a 25-kb skeletal muscle RNA transcript. </p><p>Zeviani et al. (1988) also isolated 2 nonoverlapping cDNAs encoding human nebulin. </p><p>Wang et al. (1996) isolated 2 partial cDNA sequences of fetal skeletal muscle nebulin, and Labeit and Kolmerer (1995) obtained the nearly identical sequence of a complete 20.8-kb cDNA encoding adult nebulin (the few changes may be due to sequencing errors or polymorphisms). The 6,669-residue (773 kD) predicted protein contains 185 copies of 35-amino acid modules that can be classified into 7 types. Labeit and Kolmerer (1995) suggested alternative splicing as the explanation for developmental or tissue-specific size variants of nebulin. They speculated that features at the C-terminal end of the protein, including an SH3 domain (which is also found in yeast actin-binding protein), may anchor nebulin to the Z disc of the sarcomere. </p><p>Donner et al. (2004) found that the NEB protein contains an N-terminal glutamic acid-rich domain followed by a tropomodulin-binding region; a central region containing simple repeats, super repeats of 7 simple repeats, and a desmin-binding region; and a C-terminal titin- and myopalladin-binding region, which anchors the protein in the Z disc. They also determined that the NEB gene encodes numerous splice variants. </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">
|
|
<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>Donner et al. (2004) determined that the nebulin gene contains 183 exons in a 249-kb genomic region. The translation initiation codon is in exon 3, and the stop codon and the 3-prime untranslated region are in exon 183. The central region of the gene harbors an approximately 8.2-kb region spanning 8 exons, which is duplicated twice (exons 82 to 89, exons 90 to 97, and exons 98 to 105). The duplicated segments are 99% identical. Introns 89, 97, and 105 contain LINE-2 repetitive elements. There are 4 regions with alternatively spliced exons: exons 63 to 66, 82 to 105, 143 and 144, and 166 to 177. </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">
|
|
<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">
|
|
<p>Stedman et al. (1988) localized 2 human nebulin cDNAs from fetal muscle to chromosome 2. By hybridization to DNA isolated from rodent-human cell hybrids, Zeviani et al. (1988) assigned the human nebulin gene to chromosome 2 and, by in situ hybridization, sublocalized it to region 2q31-q32. </p><p>By fluorescence in situ hybridization, Limongi et al. (1997) demonstrated that the NEB gene is located on 2q24.2, whereas the gene encoding the alpha-1 chain of type III collagen (120180) is located on 2q32.2. The FRA2 gene common fragile site lies between the 2 genes in the 2q31 band. </p><p>Pelin et al. (1997) used radiation hybrid mapping to reassign the nebulin gene close to the microsatellite marker D2S2236 on 2q22. They concluded that the nebulin gene resides within the candidate region for NEM2 (256030), a form of autosomal recessive nemaline myopathy. </p><p>Using 5 different series of recombinant inbred strains, Schurr et al. (1991) mapped the mouse nebulin gene to proximal chromosome 2. </p>
|
|
</span>
|
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<div>
|
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<br />
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>In many tissues, actin monomers polymerize into actin (thin) filaments of precise lengths. Using RNA interference, McElhinny et al. (2005) demonstrated that nebulin behaves as a 'molecular ruler' in rat cardiac and skeletal muscle. Upon nebulin knockdown, preexisting thin filaments in cultured rat cardiac muscle cells were dramatically elongated from their pointed ends; the barbed ends were unaffected. When the thin filaments were depolymerized, myocytes with decreased nebulin levels reassembled them to unrestricted lengths. Finally, knockdown of nebulin in rat skeletal myotubes revealed its involvement in myofibrillogenesis. McElhinny et al. (2005) concluded that nebulin has a role in specifying and maintaining the length of actin thin filaments in striated muscle. </p><p>In mice, Takano et al. (2010) found that Igf1 (147440)-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-Wasp (605056) at the Z bands of myofibrils by interfering with glycogen synthase kinase-3-beta (GSK3B; 605004). Although N-Wasp is known to be an activator of the Arp2/3 complex (see 604221) to form branched actin filaments, the nebulin-N-Wasp complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-Wasp was required for Igf1-induced muscle hypertrophy. Takano et al. (2010) concluded that their findings presented the mechanisms of IGF1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Nemaline Myopathy 2</em></strong></p><p>
|
|
In affected members of 5 unrelated families of different ethnic origins with congenital autosomal recessive nemaline myopathy-2 (NEM2; 256030), Pelin et al. (1999) identified 6 different mutations in the NEB gene (161650.0001-161650.0006). All of the mutations were located within the M162-M185 segment. In 2 families with consanguineous parents, the patients were homozygous for point mutations. In 1 family with nonconsanguineous parents, the affected sibs were compound heterozygotes for 2 different mutations, and in 2 further families with 1 detected mutation each, haplotypes were compatible with compound heterozygosity. Immunofluorescence studies with antibodies specific to the C-terminal region of nebulin indicated that the mutations may cause protein truncation possibly associated with loss of fiber-type diversity, which may be relevant to disease pathogenesis. </p><p>In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy, Anderson et al. (2004) identified a 2,502-bp deletion in the NEB gene (ex55del; 161650.0007). Screening for this mutation in a random sample of 4,090 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 108. </p><p>In 7 patients from 4 unrelated Finnish families, 2 of whom were consanguineous, with NEM2 manifest as distal myopathy with onset in childhood or adulthood, Wallgren-Pettersson et al. (2007) identified homozygous missense mutations in the NEB (T5681P, 161650.0008 and S4665I, 161650.0009). The mutations segregated with the disorder in the families from whom DNA was available. Functional studies of the mutation were not performed, but Wallgren-Pettersson et al. (2007) noted that both missense mutations had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more severe typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. </p><p><strong><em>Arthrogryposis Multiplex Congenita 6</em></strong></p><p>
|
|
In affected infants from 5 unrelated families with arthrogryposis multiplex congenita-6 (AMC6; 619334), Wallgren-Pettersson et al. (2002) identified mutations in the NEB gene. All the mutations were predicted to result in premature termination and a loss of function with absence of the C-terminus of the protein. One of the families of French descent (family 1) had previously been reported by Pelin et al. (1999) (family 3) as having NEM2, but Wallgren-Pettersson et al. (2002) stated that the phenotype was more consistent with AMC6 (see 161650.0003 and 161650.0004). </p><p>In 2 brothers with AMC6, Lawlor et al. (2011) identified compound heterozygous loss-of-function mutations in the NEB gene (161650.0012 and 161650.0013). The mutations, which were found by deep sequencing of the NEB gene, segregated with the disorder in the family. Western blot analysis of skeletal muscle tissue from 1 of the patients showed significantly decreased nebulin levels compared to controls. In vitro mechanical studies of patient-derived myofibers showed that they had decreased tension and impaired force generation, which the authors suggested could be explained by altered cross-bridge cycling kinetics. The severe phenotype may correlate with the significant decrease in nebulin protein levels. </p><p>Yonath et al. (2012) reported 4 unrelated pregnancies with abnormal prenatal ultrasound findings in fetuses with AMC6. In each family, 1 or both of the parents was of Ashkenazi Jewish descent, and the common exon 55 deletion in the NEB gene (161650.0007) was found in the heterozygous state in the patients and in unaffected parents. A second pathogenic NEB mutation was found in 3 of the patients; a second mutation could not be identified in 1 of the patients. </p><p>In twin male fetuses, conceived of consanguineous parents, with AMC6, Todd et al. (2015) identified a homozygous nonsense mutation in the NEB gene (R974X; 161650.0010). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Postmortem examination showed joint contractures, talipes, multiple pterygia, hypertelorism, and cystic hygromas. A previous fetus was therapeutically aborted due to hydrops fetalis at 19 weeks' gestation. Functional studies of the variant and studies of patient cells were not performed. In affected patients from 3 additional families diagnosed with fetal akinesia, a heterozygous splice site, frameshift, or truncating mutation in the NEB gene was found. A second pathogenic mutation was not found in these patients, but there was evidence for autosomal recessive inheritance, suggesting that the affected fetuses carried a second pathogenic variant. Todd et al. (2015) noted the difficulty in screening the nebulin gene for mutations because of its large size and because next-generation sequencing data may not accurately identify pathogenic small copy number variations. These 4 families were ascertained from a cohort of 38 families with severe neuromuscular disease apparent before or at birth. </p><p>In 2 sib fetuses with AMC6, Ahmed et al. (2018) identified compound heterozygous nonsense mutations in the NEB gene (Y6262X, 161650.0014 and Y6327X, 161650.0015). The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family had previously been reported by Lehtokari et al. (2014). Functional studies of the variants and studies of patient cells were not performed. </p><p>In a male fetus, conceived of consanguineous Lebanese parents, with AMC6, Rocha et al. (2021) identified a homozygous splice site mutation in the NEB gene (161650.0016). The mutation, which was found by next-generation sequencing, segregated in the family, with both parents heterozygous carriers. The mutation was not present in the gnomAD database. Functional studies of the variant were not performed. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
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</h4>
|
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</div>
|
|
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<span class="mim-text-font">
|
|
<p>Donner et al. (2004) found that alternatively spliced exons 143 and 144 of the NEB gene give rise to 2 different transcripts that vary between muscle types and between muscles of different developmental stages. Alternatively spliced exons 166 to 177 express at least 20 different transcripts in adult human tibialis anterior muscle alone. Donner et al. (2004) suggested that the extensive alternative splicing of NEB may explain why nemaline myopathy patients with homozygous truncating mutations show expression of the C terminus of the protein. The use of alternative transcripts may also explain why severe phenotypes are rare among patients with 2 truncating mutations. </p><p>Using denaturing high-performance liquid chromatography (DHPLC), Lehtokari et al. (2006) identified 45 novel mutations in the NEB gene in affected members of 44 unrelated families with nemaline myopathy. Mutations were identified in patients representing all clinical categories of disease severity. The majority (55%) of mutations were frameshift or nonsense mutations resulting in premature termination of the protein. Mutations were distributed throughout the gene, with no obvious hotspots. Lehtokari et al. (2006) concluded that mutations in the NEB gene are the most common cause of nemaline myopathy. </p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, Lehtokari et al. (2014) found that the most common types of mutations were splice-site mutations (34%), followed by frameshift (32%), nonsense (23%), and finally missense (7%). The vast majority of patients had compound heterozygous mutations. There were no apparent genotype/phenotype correlations. </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">
|
|
<strong>Animal Model</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">
|
|
<p>Witt et al. (2006) found that Neb -/- mice showed growth retardation 1 day after birth and did not survive beyond week 3. All Neb -/- mice developed a stiff gait and kyphosis, but they could walk up to week 3. Between days 10 and 20, Neb -/- mice developed progressive muscle weakness. Microarray analysis identified 40 differentially expressed genes in Neb -/- mice, and RT-PCR analysis confirmed upregulation of sarcolipin (SLN; 602203), S100a4 (114210), S100a9 (123886), desmoplakin (DSP; 125647), and Ankrd2 (610734). Characterization of skeletal myofibrils showed that absence of Neb caused loss of thin filament length control and pointed end capping in skeletal muscle tissues. However, the genes dysregulated in Neb -/- skeletal muscle were not differentially expressed in Neb -/- myocardium, indicating that nebulin is not a ruler molecule for thin filaments in myocardium. Neb was required to fine-tune calcium-dependent contractility, and consequently, loss of Neb resulted in abnormal calcium sensitivity and Z-disk morphology in skeletal muscle. Furthermore, Neb played important roles in maintaining physiologic Z-disk width and protein composition in skeletal tissues, and its absence led to formation of nemaline bodies and wide Z-disks in mice, recapitulating the phenotype of human nemaline myopathy. Further analysis demonstrated that the C-terminal region of Neb interacted with CapZ (see 601580) and titin (TTN; 188840), thereby linking these 2 ruler molecules implied in Z-disk width specification. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>16 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NEMALINE MYOPATHY 2</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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NEB, 1-BP DEL, G, EX165
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<br />
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|
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SNP: rs1057515573,
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|
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ClinVar: RCV000015090, RCV005016266
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected sibs from a British family (family 1) with nemaline myopathy-2 (NEM2; 256030), Pelin et al. (1999) identified a heterozygous 1-bp (G) deletion in exon 165 of the NEB gene, predicted to cause a truncation of the protein at the repeat domain M166. Based on the haplotypes in this family, the authors suspected that the children's maternal allele harbored an as yet unknown NEB mutation. The unaffected father also carried the mutation. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0002 NEMALINE MYOPATHY 2</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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NEB, 4-BP INS, EX172
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<br />
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|
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SNP: rs1057515574,
|
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|
|
|
|
|
ClinVar: RCV000015091
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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 Finnish child (family 2) with nemaline myopathy-2 (NEM2; 256030), Pelin et al. (1999) identified a 4-bp (GTTT) duplication/insertion in exon 172 of the NEB gene encoding part of the repeat domains M172 and M173. The child had inherited the mutation from her unaffected mother. The duplication was predicted to cause a frameshift leading to a stop codon in the beginning of exon 173, and truncation of the protein from domain M173. Haplotype analysis suggested that the child had inherited a different, unidentified, mutation from her unaffected father. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0003 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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NEB, 2-BP DEL, AG, EX172
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<br />
|
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|
|
SNP: rs1553603400,
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|
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|
|
|
|
|
ClinVar: RCV000673087, RCV002280821
|
|
|
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|
|
</span>
|
|
</div>
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|
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|
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|
<div>
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<span class="mim-text-font">
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|
<p>In 2 sibs, born of unrelated French parents (family 3) with arthrogryposis multiplex congenita-6 (AMC6; 619334), Pelin et al. (1999) identified compound heterozygous mutations in the NEB gene: a 2-bp (AG) deletion in exon 172 and a 2-bp (GA) deletion in exon 181 (161650.0004). The first mutation would lead to a stop codon in the beginning of exon 173 and a truncation of the protein from domain M173. The second mutation would lead to a stop codon in exon 181 and truncation of the protein from domain M182. Exon 181 is within the alternatively spliced region of NEB, and the maternal mutation may therefore affect only some of the nebulin isoforms. Each unaffected parent was heterozygous for 1 of the mutations, confirming segregation and autosomal recessive inheritance. Although Pelin et al. (1999) reported that these children had nemaline myopathy-2 (NEM2; 256030), Wallgren-Pettersson et al. (2002) stated that, on reexamination, these patients (family 1 in their report) had the severe form of the disorder with arthrogryposis and no spontaneous movements; both infants died in the first weeks of life. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</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>.0004 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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NEB, 2-BP DEL, GA, EX181
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<br />
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SNP: rs1559154278,
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|
ClinVar: RCV000015093
|
|
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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>For discussion of the 2-bp (GA) deletion in exon 181 of the NEB gene that was found in compound heterozygous state in 2 infant sibs with arthrogryposis multiple congenita-6 (AMC6; 619334) by Pelin et al. (1999), see 161650.0003. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 NEMALINE MYOPATHY 2</strong>
|
|
</span>
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|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
NEB, GLU6636TER
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<br />
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SNP: rs121913662,
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|
|
gnomAD: rs121913662,
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|
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|
|
ClinVar: RCV000015094
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|
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|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Pelin et al. (1999) found that a British child with autosomal recessive nemaline myopathy (NEM2; 256030), whose parents were consanguineous (family 5), had a homozygous G-to-T transversion in exon 185 of the NEB gene, resulting in a glu6636-to-ter (E6636X) substitution. The mutation was predicted to result in the loss of the last 134 amino acids of the protein, from the beginning of the serine-rich domain of the C-terminal region of nebulin. </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>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 NEMALINE MYOPATHY 2</strong>
|
|
</span>
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|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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NEB, IVS163DS, G-C
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<br />
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SNP: rs1057515575,
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ClinVar: RCV000015095
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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 the only affected child with nemaline myopathy-2 (NEM2; 256030) of a consanguineous German family of Turkish descent (family 4), Pelin et al. (1999) found homozygosity for a G-to-C transversion in the last codon of exon 163 of the NEB gene. The mutation interfered with the 5-prime consensus splice site of intron 163 and was predicted to cause an in-frame skipping of exon 163 or partial retention of intron 163, because of activation of a cryptic splice site 100-bp downstream in intron 163. The latter mRNA had a stop codon 36-bp downstream of exon 163. The abnormally spliced mRNA was seen as 2 distinct RT-PCR products different from the control mRNA. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NEMALINE MYOPATHY 2</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
ARTHROGRYPOSIS MULTIPLEX CONGENITA 6, INCLUDED
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
NEB, 2,502-BP DEL, EX55 DEL
|
|
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|
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<br />
|
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|
|
SNP: rs80358246,
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|
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|
|
|
|
|
ClinVar: RCV000015096, RCV001449896
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Nemaline Myopathy 2</em></strong></p><p>
|
|
In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy (NEM2; 256030), Anderson et al. (2004) identified a homozygosity for a 2,502-bp deletion completely encompassing exon 55 and parts of introns 54 and 55 of the NEB gene, predicted to result in a transcript encoding 35 fewer amino acids. Screening for this mutation in a random sample of 4,090 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 108. </p><p>Lehtokari et al. (2009) identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by Anderson et al. (2004). Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect. </p><p>Ottenheijm et al. (2009) studied the muscular phenotype of nemaline myopathy patients with NEB exon 55 deletion (NM-NEB). SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. Ottenheijm et al. (2009) hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations. </p><p><strong><em>Arthrogryposis Multiplex Congenita 6</em></strong></p><p>
|
|
Yonath et al. (2012) reported 4 unrelated pregnancies with abnormal prenatal ultrasound findings in fetuses with arthrogryposis multiplex congenita-6 (AMC6; 619334). In each family, 1 or both of the parents was of Ashkenazi Jewish descent, and the common exon 55 deletion in the NEB gene was found in the heterozygous state in the patients and in unaffected parents. A second pathogenic NEB mutation was found in 3 of the patients; a second mutation could not be identified in 1 of the patients. Prenatal ultrasound showed polyhydramnios, decreased fetal movements, clubfoot, and clenched hands. All patients showed severe hypotonia after birth, and all died within the first months of life. </p><p>Feingold-Zadok et al. (2017) identified this mutation in 2 fetal sibs with AMC6 from an Ashkenazi Jewish family (family 1), in compound heterozygosity with a splice site mutation. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEMALINE MYOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, THR5681PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs761232641,
|
|
|
|
|
|
gnomAD: rs761232641,
|
|
|
|
|
|
ClinVar: RCV000611555, RCV004732973
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients from 2 unrelated Finnish families, one of which was consanguineous, with nemaline myopathy-2 (NEM2; 256030) manifest as distal myopathy with onset in childhood or adulthood, Wallgren-Pettersson et al. (2007) identified a homozygous mutation (g.207181A-C, NT_005403) in exon 151 of the NEB gene, resulting in a thr5681-to-pro (T5681P) substitution. The mutation segregated with this disorder in the families and was not found in 300 Finnish control chromosomes. Functional studies of the mutation were not performed, but Wallgren-Pettersson et al. (2007) noted that T5681P had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. Lehtokari et al. (2014) referred to this mutation as THR7417PRO (T7417P), resulting from a c.22249A-C transversion (c.22249A-C, NM_001271208.1), and noted that Marttila et al. (2014) found that the variant reduces the affinity of nebulin for tropomyosin. Marttila et al. (2014) referred to the mutation as THR7382PRO (c.22144A-C, NM_001164507.1). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEMALINE MYOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, SER4665ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs191579691,
|
|
|
|
|
|
gnomAD: rs191579691,
|
|
|
|
|
|
ClinVar: RCV000589010, RCV000601389
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Finnish women, one of which was born of consanguineous parents, with nemaline myopathy-2 (NEM2; 256030) manifest as distal myopathy with onset in childhood or adulthood, Wallgren-Pettersson et al. (2007) identified a homozygous mutation in exon 122 (g.171944G-T, NT_005403) of the NEB gene, resulting in a ser4665-to-ile (S4665I) substitution. The mutation segregated with the disorder in 1 of the families; DNA was not available from other members of the second family. The mutation was not found in 188 Finnish control chromosomes nor in 90 additional control chromosomes from the same geographic region. Functional studies of the variant were not performed, but Wallgren-Pettersson et al. (2007) noted that S4665I had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. Lehtokari et al. (2014) referred to this mutation as SER6366ILE (S6366I), resulting from a c.19097G-T transversion (c.19097G-T, NM_001271208.1) and noted that Marttila et al. (2014) found that the variant increases nebulin-actin affinity. </p><p>Lehtokari et al. (2014) reported another Finnish patient with distal nemaline myopathy who was compound heterozygous for the S6366I mutation and a splice site variant in the NEB gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, ARG974TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553548666,
|
|
|
|
|
|
|
|
ClinVar: RCV000530974, RCV001449887, RCV004017670
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In twin male fetuses, conceived of consanguineous parents (family 9), with arthrogryposis multiplex congenita-6 (AMC6; 619334) presenting as fetal akinesia with lethal multiple pterygia syndrome, Todd et al. (2015) identified a homozygous c.2920C-T transition (c.2920C-T, NM_001164508) in exon 29 of the NEB gene, predicted to result in an arg974-to-ter (R974X) substitution. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the ExAC database. Postmortem examination showed joint contractures, talipes, multiple pterygia, hypertelorism, and cystic hygromas. A previous fetus was therapeutically aborted due to hydrops fetalis at 19 weeks' gestation. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, IVS74DS, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1336053002,
|
|
|
|
|
|
|
|
ClinVar: RCV000611131
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male fetus, conceived of consanguineous Egyptian parents, with arthrogryposis multiplex congenita-6 (AMC6; 619334), Abdalla et al. (2017) identified a homozygous G-to-T transversion in intron 74 of the NEB gene (c.10872+1G-T, ENST00000427231.2). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to disrupt an essential splice site. A similarly affected fetus from this family was therapeutically aborted at 20 weeks' gestation; DNA was not available from that patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, IVS13DS, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398124167,
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|
|
|
|
|
gnomAD: rs398124167,
|
|
|
|
|
|
ClinVar: RCV000174538, RCV000790650, RCV001174709, RCV001449897, RCV002477236
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with arthrogryposis multiplex congenita-6 (AMC6; 619334), Lawlor et al. (2011) identified compound heterozygous loss-of-function mutations in the NEB gene: a G-to-T transversion in intron 13 (c.1152+1G-T, NG_009382.1), predicted to result in a splice site alteration, and a 2-bp deletion in exon 81 (c.11318_11319delAG; 161650.0013), predicted to result in a frameshift and premature termination (Lys3774ArgfsTer10). The mutations, which were found by deep sequencing of the NEB gene, segregated with the disorder in the family. Neither mutation was present in 236 control chromosomes. Western blot analysis of skeletal muscle from 1 of the patients showed significantly decreased nebulin levels compared to controls. In vitro mechanical studies of patient-derived myofibers showed that they had decreased tension and impaired force generation, which the authors suggested could be explained by altered cross-bridge cycling kinetics. The severe phenotype may correlate with the significant decrease in nebulin protein levels. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NEB, 2-BP DEL, 11318AG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2153972327,
|
|
|
|
|
|
|
|
ClinVar: RCV001449898
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 2-bp deletion in exon 81 of the NEB gene (c.11318_11319delAG, NG_009382.1), predicted to result in a frameshift and premature termination (Lys3774ArgfsTer10), that was found in compound heterozygous state in 2 brothers with arthrogryposis multiplex congenita-6 (AMC6; 619334) by Lawlor et al. (2011), see 161650.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
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NEB, TYR6262TER
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<br />
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SNP: rs374874999,
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gnomAD: rs374874999,
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ClinVar: RCV001449899
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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 sib fetuses with arthrogryposis multiplex congenita-6 (AMC6; 619334), Ahmed et al. (2018) identified compound heterozygous nonsense mutations in the NEB gene: a c.18786C-G transversion (c.18786C-G, NM_001271208.1), resulting in a tyr6262-to-ter (Y6262X) substitution, and a c.18981C-G transversion, resulting in a tyr6327-to-ter (Y6327X; 161650.0015) substitution. The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family had previously been reported by Lehtokari et al. (2014). Functional studies of the variants were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0015 ARTHROGRYPOSIS MULTIPLEX CONGENITA 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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NEB, TYR6327TER
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<br />
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SNP: rs761964375,
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gnomAD: rs761964375,
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ClinVar: RCV000673447, RCV001449900
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.18981C-G transversion (c.18981C-G, NM_001271208.1) in the NEB gene, resulting in a tyr6327-to-ter (Y6327X) substitution, that was found in compound heterozygous state in 2 sib fetuses with arthrogryposis multiplex congenita-6 (AMC6; 619334) by Ahmed et al. (2018), see 161650.0014. </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>.0016 ARTHROGRYPOSIS MULTIPLEX CONGENITA 6</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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NEB, IVS122AS, G-T, -1
|
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|
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<br />
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|
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SNP: rs2153702473,
|
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|
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ClinVar: RCV001449901
|
|
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a male fetus, conceived on consanguineous Lebanese parents, with arthrogryposis multiplex congenita-6 (AMC6; 619334), Rocha et al. (2021) identified a homozygous G-to-T transition in intron 22 (c.19102-1G-T, NM_001164508) of the NEB gene, predicted to result in a splicing defect. The mutation, which was found by next-generation sequencing, segregated in the family, with both parents heterozygous carriers. The mutation was not present in the gnomAD database. Functional studies of the variant were not performed. </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>REFERENCES</strong>
|
|
</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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<ol>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abdalla, E., Ravenscroft, G., Zayed, L., Beecroft, S. J., Laing, N. G.
|
|
<strong>Lethal multiple pterygium syndrome: a severe phenotype associated with a novel mutation in the nebulin gene.</strong>
|
|
Neuromusc. Disord. 27: 537-541, 2017.
|
|
|
|
|
|
[PubMed: 28336317]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2017.01.013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., Saunders, C.
|
|
<strong>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</strong>
|
|
Am. J. Med. Genet. 176A: 359-367, 2018.
|
|
|
|
|
|
[PubMed: 29274205]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.38577]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y.
|
|
<strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong>
|
|
Hum. Genet. 115: 185-190, 2004.
|
|
|
|
|
|
[PubMed: 15221447]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-004-1140-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, K., Sandbacka, M., Lehtokari, V.-L., Wallgren-Pettersson, C., Pelin, K.
|
|
<strong>Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts.</strong>
|
|
Europ. J. Hum. Genet. 12: 744-751, 2004.
|
|
|
|
|
|
[PubMed: 15266303]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201242]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Feingold-Zadok, M., Chitayat, D., Chong, K., Injeyan, M., Shannon, P., Chapmann, D., Maymon, R., Pillar, N., Reish, O.
|
|
<strong>Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita.</strong>
|
|
Prenatal Diag. 37: 144-150, 2017.
|
|
|
|
|
|
[PubMed: 27933661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/pd.4977]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Labeit, S., Kolmerer, B.
|
|
<strong>The complete primary structure of human nebulin and its correlation to muscle structure.</strong>
|
|
J. Molec. Biol. 248: 308-315, 1995.
|
|
|
|
|
|
[PubMed: 7739042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-2836(95)80052-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lawlor, M. W., Ottenheijm, C. A., Lehtokari, V.-L., Cho, K., Pelin, K., Wallgren-Pettersson, C., Granzier, H., Beggs, A. H.
|
|
<strong>Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy.</strong>
|
|
Skeletal Muscle 1: 23, 2011.
|
|
|
|
|
|
[PubMed: 21798101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/2044-5040-1-23]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C.
|
|
<strong>The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.</strong>
|
|
Neuromusc. Disord. 19: 179-181, 2009.
|
|
|
|
|
|
[PubMed: 19232495]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2008.12.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C.
|
|
<strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong>
|
|
Hum. Mutat. 35: 1418-1426, 2014.
|
|
|
|
|
|
[PubMed: 25205138]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22693]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C.
|
|
<strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
|
|
Hum. Mutat. 27: 946-956, 2006.
|
|
|
|
|
|
[PubMed: 16917880]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20370]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Limongi, M. Z., Pelliccia, F., Rocchi, A.
|
|
<strong>Assignment of the human nebulin gene (NEB) to chromosome band 2q24.2 and the alpha-1 (III) collagen gene (COL3A1) to chromosome band 2q32.2 by in situ hybridization: the FRA2G common fragile site lies between the two genes in the 2q31 band.</strong>
|
|
Cytogenet. Cell Genet. 77: 259-260, 1997.
|
|
|
|
|
|
[PubMed: 9284930]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000134590]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marttila, M., Hanif, M., Lemola, E., Nowak, K. J., Laitila, J., Gronholm, M., Wallgren-Pettersson, C., Pelin, K.
|
|
<strong>Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations.</strong>
|
|
Skeletal Muscle 4: 15, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 25110572]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/2044-5040-4-15]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McElhinny, A. S., Schwach, C., Valichnac, M., Mount-Patrick, S., Gregorio, C. C.
|
|
<strong>Nebulin regulates the assembly and lengths of the thin filaments in striated muscle.</strong>
|
|
J. Cell Biol. 170: 947-957, 2005.
|
|
|
|
|
|
[PubMed: 16157704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.200502158]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H.
|
|
<strong>Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.</strong>
|
|
Hum. Molec. Genet. 18: 2359-2369, 2009.
|
|
|
|
|
|
[PubMed: 19346529]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp168]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
|
|
<strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.
|
|
|
|
|
|
[PubMed: 10051637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.5.2305]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
|
|
<strong>Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.</strong>
|
|
Europ. J. Hum. Genet. 5: 229-234, 1997.
|
|
|
|
|
|
[PubMed: 9359044]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rocha, M. L., Dittmayer, C., Uruha, A., Korinth, D., Chaoui, R., Schlembach, D., Rossi, R., Pelin, K., Suk, E. K., Schmid, S., Goebel, H. H., Schuelke, M., Stenzel, W., Englert, B.
|
|
<strong>A novel mutation in NEB causing foetal nemaline myopathy with arthrogryposis during early gestation.</strong>
|
|
Neuromusc. Disord. 31: 239-245, 2021.
|
|
|
|
|
|
[PubMed: 33376055]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2020.11.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schurr, E., Skamene, E., Gros, P.
|
|
<strong>Mapping of the gene coding for the muscle protein nebulin (Neb) to the proximal region of mouse chromosome 2.</strong>
|
|
Cytogenet. Cell Genet. 57: 214-216, 1991.
|
|
|
|
|
|
[PubMed: 1683831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133150]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stedman, H., Browning, K., Oliver, N., Oronzi-Scott, M., Fischbeck, K., Sarkar, S., Sylvester, J., Schmickel, R., Wang, K.
|
|
<strong>Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2.</strong>
|
|
Genomics 2: 1-7, 1988.
|
|
|
|
|
|
[PubMed: 2838409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(88)90102-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takano, K., Watanabe-Takano, H., Suetsugu, S., Kurita, S., Tsujita, K., Kimura, S., Karatsu, T., Takenawa, T., Endo, T.
|
|
<strong>Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.</strong>
|
|
Science 330: 1536-1540, 2010.
|
|
|
|
|
|
[PubMed: 21148390]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1197767]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., Haliloglu, G., Talim, B., Akcoren, Z., Kariminejad, A., Cairns, A., Clarke, N. F., and 14 others.
|
|
<strong>Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.</strong>
|
|
Orphanet J. Rare Dis. 10: 148, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 26578207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/s13023-015-0364-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K.
|
|
<strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong>
|
|
Neuromusc. Disord. 12: 674-679, 2002.
|
|
|
|
|
|
[PubMed: 12207937]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0960-8966(02)00065-2]
|
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|
|
|
</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
|
Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B.
|
|
<strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong>
|
|
Brain 130: 1465-1476, 2007.
|
|
|
|
|
|
[PubMed: 17525139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awm094]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, K., Knipfer, M., Huang, Q.-Q., van Heerden, A., Hsu, L. C.-L., Gutierrez, G., Quian, X.-L., Stedman, H.
|
|
<strong>Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture: sequence motifs and affinity profiles of tandem repeats and terminal SH3.</strong>
|
|
J. Biol. Chem. 271: 4304-4314, 1996.
|
|
|
|
|
|
[PubMed: 8626778]
|
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[Full Text: https://doi.org/10.1074/jbc.271.8.4304]
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Witt, C. C., Burkart, C., Labeit, D., McNabb, M., Wu, Y., Granzier, H., Labeit, S.
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<strong>Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo.</strong>
|
|
EMBO J. 25: 3843-3855, 2006.
|
|
|
|
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|
[PubMed: 16902413]
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|
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[Full Text: https://doi.org/10.1038/sj.emboj.7601242]
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Yonath, H., Reznik-Wolf, H., Berkenstadt, M., Eisenberg-Barzilai, S., Lehtokari, V.-L., Wallgren-Pettersson, C., Mehta, L., Achiron, R., Gilboa, Y., Polak-Charcon, S., Winder, T., Frydman, M., Pras, E.
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<strong>Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy.</strong>
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Prenatal Diag. 32: 70-74, 2012.
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[PubMed: 22367672]
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[Full Text: https://doi.org/10.1002/pd.2905]
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Zeviani, M., Darras, B. T., Rizzuto, R., Salviati, G., Betto, R., Bonilla, E., Miranda, A. F., Du, J., Samitt, C., Dickson, G., Walsh, F. S., DiMauro, S., Francke, U., Schon, E. A.
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<strong>Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32.</strong>
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Genomics 2: 249-256, 1988.
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[PubMed: 3397062]
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[Full Text: https://doi.org/10.1016/0888-7543(88)90009-2]
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Bao Lige - updated : 09/01/2021<br>Cassandra L. Kniffin - updated : 05/21/2021<br>Cassandra L. Kniffin - updated : 03/27/2018<br>Ada Hamosh - updated : 1/19/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 10/16/2009<br>Patricia A. Hartz - updated : 10/19/2006<br>Cassandra L. Kniffin - updated : 9/19/2006<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Cassandra L. Kniffin - updated : 4/4/2005<br>Patricia A. Hartz - updated : 10/19/2004<br>Victor A. McKusick - updated : 4/28/1999<br>Victor A. McKusick - updated : 10/30/1997<br>Victor A. McKusick - updated : 10/20/1997<br>Alan F. Scott - updated : 5/20/1996
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Victor A. McKusick : 12/4/1987
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