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Entry
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- *162280 - NEUROFILAMENT PROTEIN, LIGHT POLYPEPTIDE; NEFL
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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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="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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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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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</form>
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<p />
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</div>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*162280</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/162280">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>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
|
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
|
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
|
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</a>
|
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</h4>
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</div>
|
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000277586;t=ENST00000610854" 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=4747" 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=162280" 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=ENSG00000277586;t=ENST00000610854" 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_006158" 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_006158" 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=162280" 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=01206&isoform_id=01206_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/NEFL" 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/1279504,4261757,19584317,24658018,25987101,32394392,44890585,62511894,67654831,105990539,119584002,119584003,119584004,119584005,193785349,193786724,194386690,957949888,957949891" 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/P07196" 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=4747" 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=ENSG00000277586;t=ENST00000610854" 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=NEFL" 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=NEFL" 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+4747" 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/NEFL" 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:4747" 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/4747" 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=chr8&hgg_gene=ENST00000610854.2&hgg_start=24950955&hgg_end=24956612&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:7739" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7739" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=162280[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=162280[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://gnomad.broadinstitute.org/gene/ENSG00000277586" 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.gwascentral.org/search?q=NEFL" 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=NEFL" 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.molgen.ua.ac.be/CMTMutations/" 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=NEFL&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/PA31542" 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:7739" 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:97313" 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/NEFL#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:97313" 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/4747/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/OMIA000545/" 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=4747" 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-060312-44" 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="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:4747" 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=NEFL&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 717012004, 719980006<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
162280
|
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</span>
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</span>
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</div>
|
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
|
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NEUROFILAMENT PROTEIN, LIGHT POLYPEPTIDE; NEFL
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
NEUROFILAMENT PROTEIN, LIGHT CHAIN; NFL<br />
|
|
NF68
|
|
</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NEFL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NEFL</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/8/137?start=-3&limit=10&highlight=137">8p21.2</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:24950955-24956612&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'})">8:24,950,955-24,956,612</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
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Location
|
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</th>
|
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<th>
|
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Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=617882,607734,607684" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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</th>
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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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<span class="mim-font">
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<a href="/geneMap/8/137?start=-3&limit=10&highlight=137">
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8p21.2
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</a>
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</td>
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<span class="mim-font">
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Charcot-Marie-Tooth disease, dominant intermediate G
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/617882"> 617882 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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Charcot-Marie-Tooth disease, type 1F
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607734"> 607734 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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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<span class="mim-font">
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Charcot-Marie-Tooth disease, type 2E
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607684"> 607684 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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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/162280" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/162280" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<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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<strong>Description</strong>
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<p>The NEFL gene encodes the neurofilament light polypeptide, a subunit that forms type IV intermediate filament heteropolymers, which are a major component of the neuronal cytoskeleton (summary by <a href="#3" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Marinakis, N. S., Schmitz-Abe, K., Ciarlini, P. D. S. C., Sargent, J. C., Markianos, K., De Girolami, U., Chad, D. A., Beggs, A. H. <strong>Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.</strong> JAMA Neurol. 71: 1413-1420, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25264603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25264603</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25264603[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/10.1001/jamaneurol.2014.1432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25264603">Agrawal et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25264603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cytoplasmic intermediate filaments (IF) can be divided into 5 subclasses based on their biochemical properties, immunologic specificity and tissue distribution: keratin (<a href="/entry/139350">139350</a>, <a href="/entry/148030">148030</a>) filaments in epithelial cells, vimentin (<a href="/entry/193060">193060</a>) filaments in cells of mesenchymal origin, desmin (<a href="/entry/125660">125660</a>) in muscle cells, glial filaments in astrocytes, and neurofilaments in neurons. The different types of intermediate filament proteins share common structural features. Neurofilaments are composed of 3 neuron-specific proteins with apparent molecular masses of 68 kD (NFL), 125 kD (NFM), and 200 kD (NFH) on SDS-gel electrophoresis (summary by <a href="#15" class="mim-tip-reference" title="Julien, J.-P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., Mushynski, W. <strong>The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.</strong> Biochim. Biophys. Acta 909: 10-20, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3034332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3034332</a>] [<a href="https://doi.org/10.1016/0167-4781(87)90041-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3034332">Julien et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3034332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<br />
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<div>
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<a id="cloning" class="mim-anchor"></a>
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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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<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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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p><a href="#15" class="mim-tip-reference" title="Julien, J.-P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., Mushynski, W. <strong>The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.</strong> Biochim. Biophys. Acta 909: 10-20, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3034332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3034332</a>] [<a href="https://doi.org/10.1016/0167-4781(87)90041-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3034332">Julien et al. (1987)</a> isolated the genomic copy of the human NFL gene using an NFL cDNA probe. After transfection into mouse L-cells, the cloned gene was transcribed into 2 mRNAs approximately 2.6 and 4.3 kb long. The different sequence data show that the intermediate filament proteins contain a similar alpha-helical domain of conserved length capable of forming coiled-coils. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3034332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<br />
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</div>
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<div>
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<a id="geneStructure" class="mim-anchor"></a>
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>The vimentin, desmin, and glial fibrillary acidic protein genes each contains 8 introns at identical positions, 6 of the introns being located within the regions encoding alpha-helical sequences. A majority of the introns in the less closely related keratin genes occurred at similar or identical positions. The NFL gene was found by <a href="#15" class="mim-tip-reference" title="Julien, J.-P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., Mushynski, W. <strong>The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.</strong> Biochim. Biophys. Acta 909: 10-20, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3034332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3034332</a>] [<a href="https://doi.org/10.1016/0167-4781(87)90041-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3034332">Julien et al. (1987)</a> to have an unexpected intron-exon organization in that it entirely lacks introns at positions found in other members of the intermediate filament gene family. It contains only 3 introns. Possible evolutionary explanations were discussed. <a href="#16" class="mim-tip-reference" title="Lees, J. F., Shneidman, P. S., Skuntz, S. F., Carden, M. J., Lazzarini, R. A. <strong>The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it.</strong> EMBO J. 7: 1947-1955, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3138108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3138108</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03032.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3138108">Lees et al. (1988)</a> analyzed the structure of the NFH subunit. They concluded that divergence of the neural IF lineage from the nonneural IF lineage probably involved ancestral IF gene duplication rather than RNA-mediated transposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3034332+3138108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>
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<br />
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<div>
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<a id="mapping" class="mim-anchor"></a>
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<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By Southern blot analysis of DNA from hybrid cell panels and by in situ hybridization, <a href="#13" class="mim-tip-reference" title="Hurst, J., Flavell, D., Julien, J.-P., Meijer, D., Mushynski, W., Grosveld, F. <strong>The human neurofilament gene (NEFL) is located on the short arm of chromosome 8.</strong> Cytogenet. Cell Genet. 45: 30-32, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3036423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3036423</a>] [<a href="https://doi.org/10.1159/000132421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3036423">Hurst et al. (1987)</a> assigned the NEFL gene to 8p21. <a href="#27" class="mim-tip-reference" title="Somerville, M. J., McLachlan, D. R., Percy, M. E. <strong>Localization of the 68000-Da human neurofilament gene (NF68) using a murine cDNA probe.</strong> Genome 30: 499-500, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3145240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3145240</a>] [<a href="https://doi.org/10.1139/g88-083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3145240">Somerville et al. (1988)</a> also assigned this gene, which they symbolized NF68, to 8p21 by in situ hybridization. In addition, they found secondary hybridization sites at the centromeric region of chromosome 2 and on the long arm of chromosome 7, which are putative loci for other intermediate filaments. The corresponding gene for NFL, as well as that for middle-molecular-mass neurofilament protein, appears to be on chromosome 14 in the mouse (<a href="#18" class="mim-tip-reference" title="Levy, E., Liem, R. K. H., D'Eustachio, P., Cowan, N. J. <strong>Structure and evolutionary origin of the gene encoding NF-M, the middle-molecular-mass neurofilament protein.</strong> Europ. J. Biochem. 166: 71-77, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3036526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3036526</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1987.tb13485.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3036526">Levy et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3145240+3036423+3036526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<br />
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<strong>Gene Function</strong>
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<p><a href="#24" class="mim-tip-reference" title="Previtali, S. C., Zerega, B., Sherman, D. L., Brophy, P. J., Dina, G., King, R. H. M., Salih, M. M., Feltri, L., Quattrini, A., Ravazzolo, R., Wrabetz, L., Monaco, A. P., Bolino, A. <strong>Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve.</strong> Hum. Molec. Genet. 12: 1713-1723, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837694</a>] [<a href="https://doi.org/10.1093/hmg/ddg179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837694">Previtali et al. (2003)</a> detected MTMR2 (<a href="/entry/603557">603557</a>) in all cytoplasmic compartments of myelin-forming Schwann cells, as well as in the cytoplasm of non-myelin-forming Schwann cells and both sensory and motor neurons. In contrast, MTMR2 was detected in the nucleus of Schwann cells and motor neurons, but not in the nucleus of sensory neurons. NFL interacted with MTMR2 in yeast 2-hybrid screenings using both fetal brain and peripheral nerve libraries and was found to interact with MTMR2 in both Schwann cells and neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Charcot-Marie-Tooth Disease Type 2E</em></strong></p><p>
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In a large Russian family with an axonal form of Charcot-Marie-Tooth disease (CMT2E; <a href="/entry/607684">607684</a>), <a href="#20" class="mim-tip-reference" title="Mersiyanova, I. V., Perepelov, A. V., Polyakov, A. V., Sitnikov, V. F., Dadali, E. L., Oparin, R. B., Petrin, A. N., Evgrafov, O. V. <strong>A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene.</strong> Am. J. Hum. Genet. 67: 37-46, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10841809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10841809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10841809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10841809">Mersiyanova et al. (2000)</a> identified a gln333-to-pro mutation in the NEFL gene (Q333P; <a href="#0001">162280.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10841809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a transient expression system, <a href="#6" class="mim-tip-reference" title="Brownlees, J., Ackerley, S., Grierson, A. J., Jacobsen, N. J. O., Shea, K., Anderton, B. H., Leigh, P. N., Shaw, C. E., Miller, C. C. J. <strong>Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport.</strong> Hum. Molec. Genet. 11: 2837-2844, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393795</a>] [<a href="https://doi.org/10.1093/hmg/11.23.2837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393795">Brownlees et al. (2002)</a> demonstrated that the pro8-to-arg (P8R; <a href="#0003">162280.0003</a>) and Q333P (<a href="#0001">162280.0001</a>) mutant NEFL proteins, which cause CMT2E, disrupted both neurofilament assembly and axonal transport of neurofilaments in cultured mammalian cells and neurons. CMT mutant neurofilaments also perturbed the localization of mitochondria in neurons. Accumulations of neurofilaments are a pathologic feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS; <a href="/entry/105400">105400</a>), Alzheimer disease (<a href="/entry/104300">104300</a>), Parkinson disease (<a href="/entry/168600">168600</a>), dementia with Lewy bodies (<a href="/entry/127750">127750</a>), and diabetic neuropathy (see <a href="/entry/603933">603933</a>). The authors concluded that their results demonstrated that aberrant neurofilament assembly and transport can induce neurologic disease and further implicated defective neurofilament metabolism in the pathogenesis of human neurodegenerative diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Charcot-Marie-Tooth Disease Type 1F</em></strong></p><p>
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<a href="#14" class="mim-tip-reference" title="Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J.-J., Butler, I. J., Mancias, P., Papasozomenos, S. C., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., Timmerman, V. <strong>Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.</strong> Brain 126: 590-597, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566280</a>] [<a href="https://doi.org/10.1093/brain/awg059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12566280">Jordanova et al. (2003)</a> identified 6 missense mutations and a 3-bp deletion (<a href="#0004">162280.0004</a>) in the NEFL gene in patients with autosomal dominant demyelinating CMT1F (<a href="/entry/607734">607734</a>). Three of these mutations occurred in codon 8 (see, e.g., <a href="#0003">162280.0003</a>). <a href="#28" class="mim-tip-reference" title="Yamamoto, M., Yoshihara, T., Hattori, N., Sobue, G. <strong>Glu528del in NEFL is a polymorphic variant rather than a disease-causing mutation for Charcot-Marie-Tooth disease in Japan.</strong> Neurogenetics 5: 75-77, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14586770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14586770</a>] [<a href="https://doi.org/10.1007/s10048-003-0159-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14586770">Yamamoto et al. (2004)</a> presented evidence suggesting that the 3-bp deletion in the NEFL gene is a polymorphic variant rather than a disease-causing mutation in Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12566280+14586770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Charcot-Marie-Tooth Disease, Dominant Intermediate G</em></strong></p><p>
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In 4 affected members of a 3-generation German family with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; <a href="/entry/617882">617882</a>). <a href="#32" class="mim-tip-reference" title="Zuchner, S., Vorgerd, M., Sindern, E., Schroder, J. M. <strong>The novel neurofilament light (NEFL) mutation glu397lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.</strong> Neuromusc. Disord. 14: 147-157, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14733962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14733962</a>] [<a href="https://doi.org/10.1016/j.nmd.2003.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14733962">Zuchner et al. (2004)</a> identified a heterozygous missense mutation in the NEFL gene (E396K; <a href="#0010">162280.0010</a>). The mutation, which was found by direct sequencing of the NEFL gene, segregated with the disorder in the family. Two asymptomatic family members also carried the mutation: they were 21 years of age, possibly suggesting age-related incomplete penetrance. 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=14733962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Elbracht, M., Senderek, J., Schara, U., Nolte, K., Klopstock, T., Roos, A., Reimann, J., Zerres, K., Weis, J., Rudnik-Schoneborn, S. <strong>Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie-Tooth disease type 2E.</strong> Clin. Neuropath. 33: 335-343, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24887401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24887401</a>] [<a href="https://doi.org/10.5414/NP300742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24887401">Elbracht et al. (2014)</a> identified heterozygosity for the E396K mutation in the NEFL gene in 8 members of a multigenerational family with onset of CMTDIG since infancy or early childhood as well as in an unrelated patient (patient 9) with CMTDIG who had onset at age 50; he had no family history of CMT. The discrepancy in the phenotype among patients with the same mutation suggested additional genetic modifiers and broadened the phenotypic spectrum associated with this mutation. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24887401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Berciano, J., Garcia, A., Peeters, K., Gallardo, E., De Vriendt, E., Palayo-Negro, A. L., Infante, J., Jordanova, A. <strong>NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.</strong> J. Neurol. 262: 1289-1300, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25877835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25877835</a>] [<a href="https://doi.org/10.1007/s00415-015-7709-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25877835">Berciano et al. (2015)</a> identified heterozygosity for the E396K mutation in the NEFL gene in 4 affected members of a Spanish family with CMTDIG. The variant, which was found by exome sequencing of candidate disease genes, was confirmed by Sanger sequencing and segregated with the disorder. 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=25877835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Spanish woman and her son with CMTDIG, <a href="#5" class="mim-tip-reference" title="Berciano, J., Peeters, K., Garcia, A., Lopez-Alburquerque, T., Gallardo, E., Hernandez-Fabian, A., Pelayo-Negro, A. L., De Vriendt, E., Infante, J., Jordanova, A. <strong>NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.</strong> J. Neurol. 263: 361-369, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26645395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26645395</a>] [<a href="https://doi.org/10.1007/s00415-015-7985-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26645395">Berciano et al. (2016)</a> identified a heterozygous missense mutation in the NEFL gene (N98S; <a href="#0011">162280.0011</a>). The mutation was found by exome sequencing. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26645395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>NEFL Aggregation Studies</em></strong></p><p>
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<a href="#19" class="mim-tip-reference" title="Lin, H., Zhai, J., Schlaepfer, W. W. <strong>RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.</strong> Hum. Molec. Genet. 14: 3643-3659, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236762</a>] [<a href="https://doi.org/10.1093/hmg/ddi392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236762">Lin et al. (2005)</a> reported that p190RhoGEF (<a href="/entry/612790">612790</a>), an RNA-binding protein that binds to a destabilizing element in NEFL mRNA, is involved in aggregation of NEFL protein and is implicated in the pathogenesis of motor neuron degeneration. The 190RhoGEF protein coaggregated with unassembled NEFL protein, and that coaggregation was associated with downregulation of parent NEFL mRNA in neuronal cells. Coexpression of medium neurofilament (NFM; <a href="/entry/162250">162250</a>) increased NF assembly and reduced RNA-triggered aggregation as well as loss of solubility of NEFL protein. siRNA-induced downregulation of p190RhoGEF not only reduced aggregation and promoted assembly of NEFL and NFM, but also caused reversal of aggregation and recovery of NF assembly in transfected cells. Examination of transgenic models of motor neuron disease showed that prominent aggregates of p190RhoGEF and NEFL and downregulation of NEFL expression occurred in degenerating motor neurons of mice expressing untranslated NEFL RNA or a G93A-mutant SOD1 (<a href="/entry/147450">147450</a>) transgene. Moreover, aggregates of p190RhoGEF and NEFL appeared as early pathologic changes in presymptomatic G93A-mutant SOD1 transgenic mice. <a href="#19" class="mim-tip-reference" title="Lin, H., Zhai, J., Schlaepfer, W. W. <strong>RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.</strong> Hum. Molec. Genet. 14: 3643-3659, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236762</a>] [<a href="https://doi.org/10.1093/hmg/ddi392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236762">Lin et al. (2005)</a> concluded that p190RhoGEF is involved in aggregation of NEFL protein and proposed that aggregation of p190RhoGEF and NEFL may be an upstream event triggering neurotoxicity in motor neuron disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Rebelo, A. P., Abrams, A. J., Cottenie, E., Horga, A., Gonzalez, M., Bis, D. M., Sanchez-Mejias, A., Pinto, M., Buglo, E., Markel, K., Prince, J., Laura, M., and 10 others. <strong>Cryptic amyloidogenic elements in the 3-prime UTRs of neurofilament genes trigger axonal neuropathy.</strong> Am. J. Hum. Genet. 98: 597-614, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27040688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27040688</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27040688[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.02.022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27040688">Rebelo et al. (2016)</a> identified NEFL as a gene with the potential to cause abnormal and toxic protein aggregations as a result of a stop-loss mutation, i.e., a mutation that extends the 3-prime translation frame beyond the normal stop codon, resulting in the addition of cryptic amyloidogenic elements (CAE). Cultured neuronal cells expressing such frameshift NEFL mutations showed prominent toxic protein aggregations in the cytoplasm as well as rounded cells and a lack of axon-like projections, indicating that they would be pathogenic and thus could likely result in neurologic disorders. Similar findings were observed for frameshift mutations in the NEFH gene (<a href="/entry/162230">162230</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27040688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#23" class="mim-tip-reference" title="Perez-Olle, R., Jones, S. T., Liem, R. K. H. <strong>Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models.</strong> Hum. Molec. Genet. 13: 2207-2220, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15282209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15282209</a>] [<a href="https://doi.org/10.1093/hmg/ddh236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15282209">Perez-Olle et al. (2004)</a> analyzed the effects of 5 NFL mutations on the assembly and intracellular distribution of intermediate filaments (IFs), and compared the results with those obtained previously for other NFL mutations. Although all NFL mutants affected the formation of IF networks, there were differential effects on the assembly of IFs depending on the mutation. Defective transport of the mutant NFL subunits was observed for all the CMT-linked NFL mutations, but the characteristics of this defect also depended on the specific mutation. The authors concluded that defects in the assembly and transport of NFs are common to all NFL mutants studied to that time, but the exact nature of the defect appeared to be correlated with each mutant genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15282209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 review of published studies of patients with NEFL mutations, <a href="#21" class="mim-tip-reference" title="Miltenberger-Miltenyi, G., Janecke, A. R., Wanschitz, J. V., Timmerman, V., Windpassinger, C., Auer-Grumbach, M., Loscher, W. N. <strong>Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.</strong> Arch. Neurol. 64: 966-970, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620486</a>] [<a href="https://doi.org/10.1001/archneur.64.7.966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620486">Miltenberger-Miltenyi et al. (2007)</a> concluded that there are no obvious genotype/phenotype correlations. However, the authors noted that mutations in the head domain of NEFL may cause more severe slowing of nerve conduction velocities than mutations in the coil 2B domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Using homologous recombination in embryonic stem cells, <a href="#31" class="mim-tip-reference" title="Zhu, Q., Couillard-Despres, S., Julien, J.-P. <strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong> Exp. Neurol. 148: 299-316, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398473</a>] [<a href="https://doi.org/10.1006/exnr.1997.6654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398473">Zhu et al. (1997)</a> generated mice bearing a targeted disruption of the NFL gene. The absence of NFL protein resulted in dramatic reduction in the levels of Nfm and Nfh proteins in the brain and sciatic nerve, while increases for other cytoskeletal proteins, such as tubulin and GAP43 (<a href="/entry/162060">162060</a>), were detected. Despite a lack of neurofilaments and hypotrophy of axons, the NFL knockout mice developed normally and did not exhibit any overt phenotypes. However, in both heterozygous and homozygous NFL mutant mice, <a href="#31" class="mim-tip-reference" title="Zhu, Q., Couillard-Despres, S., Julien, J.-P. <strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong> Exp. Neurol. 148: 299-316, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398473</a>] [<a href="https://doi.org/10.1006/exnr.1997.6654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398473">Zhu et al. (1997)</a> observed a reduction in the normal regeneration of myelinated axons following crush injury of peripheral nerves. Using electron microscopy of nerve segments distal to the crush site, <a href="#31" class="mim-tip-reference" title="Zhu, Q., Couillard-Despres, S., Julien, J.-P. <strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong> Exp. Neurol. 148: 299-316, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398473</a>] [<a href="https://doi.org/10.1006/exnr.1997.6654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398473">Zhu et al. (1997)</a> detected abundant clusters of axonal sprouts that were indicative of retarded maturation of regenerating fibers in NFL null mice. Long-term analysis indicated that neurofilament-deficient axons have the capacity to regrow and to remyelinate, albeit at a slower rate. <a href="#31" class="mim-tip-reference" title="Zhu, Q., Couillard-Despres, S., Julien, J.-P. <strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong> Exp. Neurol. 148: 299-316, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398473</a>] [<a href="https://doi.org/10.1006/exnr.1997.6654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398473">Zhu et al. (1997)</a> concluded that neurofilaments play a role in the maturation of regenerating myelinated axons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Hirokawa, N., Takeda, S. <strong>Gene targeting studies begin to reveal the function of neurofilament proteins.</strong> J. Cell Biol. 143: 1-4, 1998. Note: Erratum: J. Cell Biol. 143: 1142 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9763415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9763415</a>] [<a href="https://doi.org/10.1083/jcb.143.1.1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9763415">Hirokawa and Takeda (1998)</a> reviewed contributions gene targeting studies had made to understanding the role of each of the neurofilament component proteins in neurofilament formation and in determination of the axonal caliber. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9763415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 immunohistochemistry and immunoblots experiments, <a href="#22" class="mim-tip-reference" title="Nguyen, M. D., Lariviere, R. C., Julien, J.-P. <strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong> Neuron 30: 135-147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343650</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00268-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343650">Nguyen et al. (2001)</a> detected a hyperphosphorylation of neurofilament proteins associated with abnormally elevated p25/p35 (see <a href="/entry/603460">603460</a>) ratio and Cdk5 (<a href="/entry/123831">123831</a>) activity in the spinal cord of transgenic mice with a gly37-to-arg (G37R) mutation in the SOD1 gene (<a href="/entry/147450#0001">147450.0001</a>), a mouse model of amyotrophic lateral sclerosis (ALS; <a href="/entry/105400">105400</a>). <a href="#22" class="mim-tip-reference" title="Nguyen, M. D., Lariviere, R. C., Julien, J.-P. <strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong> Neuron 30: 135-147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343650</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00268-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343650">Nguyen et al. (2001)</a> bred the Sod1 mutant transgene onto neurofilament mutant backgrounds and observed that the absence of NFL provoked an accumulation of unassembled neurofilament subunits in the perikaryon of motor neurons. Using double immunofluorescence microscopy, <a href="#22" class="mim-tip-reference" title="Nguyen, M. D., Lariviere, R. C., Julien, J.-P. <strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong> Neuron 30: 135-147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343650</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00268-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343650">Nguyen et al. (2001)</a> confirmed that Cdk5 and p25 colocalize with perikaryal neurofilament accumulations in SOD1(G37R) mice on the neurofilament mutant background. Immunoblotting showed that the occurrence of perikaryal neurofilament accumulations in SOD1(G37R) mice was associated with a reduction in the phosphorylation of microtubule-associated protein tau (<a href="/entry/157140">157140</a>), another p25/Cdk5 substrate. The absence of the NFL subunit extended the average life span of SOD1(G37R) mice. <a href="#22" class="mim-tip-reference" title="Nguyen, M. D., Lariviere, R. C., Julien, J.-P. <strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong> Neuron 30: 135-147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343650</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00268-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343650">Nguyen et al. (2001)</a> hypothesized that perikaryal accumulations of neurofilament proteins in motor neurons may alleviate ALS pathogenesis in Sod1 mutant mice by acting as a phosphorylation sink for Cdk5 activity, thereby reducing the detrimental hyperphosphorylation of tau and other neuronal substrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Adebola, A. A., Di Castri, T., He, C.-Z., Salvatierra, L. A., Zhao, J., Brown, K., Lin, C.-S., Worman, H. J., Liem, R. K. H. <strong>Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth type 2E phenotype.</strong> Hum. Molec. Genet. 24: 2163-2174, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25552649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25552649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25552649[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/ddu736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25552649">Adebola et al. (2015)</a> found that knockin mice heterozygous or homozygous for the Nefl P8R (<a href="#0003">162280.0003</a>) mutation were behaviorally similar to wildtype animals. The authors attributed the lack of phenotype to possible background modifier genes. In contrast, knockin mice heterozygous for the Nefl N98S (<a href="#0011">162280.0011</a>) mutation developed tremor and a hindlimb clasping phenotype as early as 1 month of age. Abnormal neuronal processes in the cerebral cortex and pons were present as soon as 7 days after birth, and these animals had multiple inclusions in cell bodies and proximal axons of spinal cord neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25552649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large Mordovian (Russian) family with autosomal dominant Charcot-Marie-Tooth disease of the axonal form (CMT2E; <a href="/entry/607684">607684</a>), <a href="#20" class="mim-tip-reference" title="Mersiyanova, I. V., Perepelov, A. V., Polyakov, A. V., Sitnikov, V. F., Dadali, E. L., Oparin, R. B., Petrin, A. N., Evgrafov, O. V. <strong>A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene.</strong> Am. J. Hum. Genet. 67: 37-46, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10841809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10841809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10841809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10841809">Mersiyanova et al. (2000)</a> found linkage to chromosome 8p21 and identified a 998A-C transversion in the first exon of the NEFL gene, resulting in a gln333-to-pro (Q333P) mutation in a conserved region. This alteration was not found in 180 normal chromosomes. No mutations in this gene were found in 20 unrelated CMT2 patients or in 26 others with an undetermined form of CMT. The authors suggested the designation CMT2E for this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10841809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In cultured mouse motor neurons, <a href="#30" class="mim-tip-reference" title="Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W. <strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong> Hum. Molec. Genet. 16: 3103-3116, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881652</a>] [<a href="https://doi.org/10.1093/hmg/ddm272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881652">Zhai et al. (2007)</a> found that expression of Q333P- and P8R (<a href="#0003">162280.0003</a>)-mutant NEFL led to progressive degeneration and loss of neuronal viability. Degenerating motor neurons showed fragmentation and loss of neuritic processes associated with disruption of the neurofilament network and aggregation of the NEFL protein. Coexpression of mutant NEFL with wildtype HSPB1 (<a href="/entry/602195">602195</a>) diminished aggregation of mutant NEFL, induced reversal of mutant NEFL aggregates, and reduced mutant NEFL-induced loss of motor neuron viability. Similarly, expression of mutant HSPB1 (S135F; <a href="/entry/602195#0001">602195.0001</a>), which causes CMT2F (<a href="/entry/606595">606595</a>) also led to progressive degeneration of motor neurons with disruption of the neurofilament network and aggregation of NEFL protein. The 2 proteins were found to associate together, and the S135F-mutant HSPB1 had a dominant effect. <a href="#30" class="mim-tip-reference" title="Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W. <strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong> Hum. Molec. Genet. 16: 3103-3116, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881652</a>] [<a href="https://doi.org/10.1093/hmg/ddm272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881652">Zhai et al. (2007)</a> suggested that disruption of the neurofilament network with aggregation of NEFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015073 OR RCV000057144 OR RCV000194357 OR RCV000414916 OR RCV000415401 OR RCV001196666 OR RCV002362585" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015073, RCV000057144, RCV000194357, RCV000414916, RCV000415401, RCV001196666, RCV002362585" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015073...</a>
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<p><a href="#11" class="mim-tip-reference" title="Georgiou, D.-M., Zidar, J., Korosec, M., Middleton, L. T., Kyriakides, T., Christodoulou, K. <strong>A novel NF-L mutation pro22-to-ser is associated with CMT2 in a large Slovenian family.</strong> Neurogenetics 4: 93-96, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12481988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12481988</a>] [<a href="https://doi.org/10.1007/s10048-002-0138-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12481988">Georgiou et al. (2002)</a> described a large 5-generation Slovenian family with autosomal dominant Charcot-Marie-Tooth disease type 2E (CMT2E; <a href="/entry/607684">607684</a>) in which all 10 affected members had a 64C-T transition in exon 1 of the NEFL gene resulting in a pro22-to-ser (P22S) substitution. Disease onset in most patients was in the first decade of life. The presenting symptoms were difficulty in walking or running, due to a slowly progressive distal weakness and wasting of the lower limbs. A steppage gait, pes cavus, and hammertoes were typically present. Over a period of 20 years after disease onset, two-thirds of patients developed upper limb involvement resulting in claw hands. All patients were ambulatory 20 to 30 years after onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12481988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fabrizi, G. M., Cavallaro, T., Angiari, C., Bertolasi, L., Cabrini, I., Ferrarini, M., Rizzuto, N. <strong>Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E.</strong> Neurology 62: 1429-1431, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15111691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15111691</a>] [<a href="https://doi.org/10.1212/01.wnl.0000120664.07186.3c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15111691">Fabrizi et al. (2004)</a> identified the P22S mutation in affected members of an Italian family with CMT2E. Sural nerve biopsy showed loss of large myelinated axons and a few swollen axons encased in a thin myelin sheath. Neurofilaments were grouped in a random orientation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15111691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Sasaki, T., Gotow, T., Shiozaki, M., Sakaue, F., Saito, T., Julien, J.-P., Uchiyama, Y., Hisanaga, S. <strong>Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie-Tooth disease mutants.</strong> Hum. Molec. Genet. 15: 943-952, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16452125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16452125</a>] [<a href="https://doi.org/10.1093/hmg/ddl011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16452125">Sasaki et al. (2006)</a> noted that the P22S mutation abolishes a phosphorylation sequence in the head domain of NEFL. In vitro functional expression studies in isolated human cells and in rat cortical neuron cultures showed that the mutant P22S or P22T NEFL proteins formed large aggregates and assembled into short twisty threads thinner than 10 nm filaments. Those threads associated with each other at their ends and entangled into large aggregates. The structure disturbance occurred during oligomer formation. Further studies showed that the pro22 mutations abolished phosphorylation of residue thr21 by CDK5 (<a href="/entry/123831">123831</a>), which normally suppresses filament assembly. However, the mutant proteins were able to be phosphorylated by protein kinase A to the same extent as wildtype, which inhibited aggregate formation in cortical neurons. The results indicated that the pro22 CMT mutation induces abnormal filament aggregates by disrupting proper oligomer formation, but demonstrated that the formation of these aggregates could be mitigated by phosphorylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16452125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs60261494 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60261494;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=rs60261494" 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=rs60261494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61491953 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61491953;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=rs61491953" 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=rs61491953" 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=RCV000015074 OR RCV000015075 OR RCV000057129" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015074, RCV000015075, RCV000057129" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015074...</a>
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<p>In members of a Belgian family with Charcot-Marie-Tooth disease type 2E (CMT2E; <a href="/entry/607684">607684</a>), <a href="#7" class="mim-tip-reference" title="De Jonghe, P., Mersiyanova, I., Nelis, E., Del Favero, J., Martin, J.-J., Van Broeckhoven, C., Evgrafov, O., Timmerman, V. <strong>Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E.</strong> Ann. Neurol. 49: 245-249, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11220745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11220745</a>] [<a href="https://doi.org/10.1002/1531-8249(20010201)49:2<245::aid-ana45>3.0.co;2-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11220745">De Jonghe et al. (2001)</a> demonstrated a double transition at nucleotides 22 to 23 (CC to AG) in exon 1 of the NEFL gene, resulting in a pro8-to-arg (P8R) substitution. The patients presented with a classic but rather severe CMT phenotype with onset in the second decade. Nerve conduction velocities were sometimes severely slowed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11220745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J.-J., Butler, I. J., Mancias, P., Papasozomenos, S. C., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., Timmerman, V. <strong>Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.</strong> Brain 126: 590-597, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566280</a>] [<a href="https://doi.org/10.1093/brain/awg059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12566280">Jordanova et al. (2003)</a> found the P8R mutation in affected members of a family segregating CMT1F (<a href="/entry/607734">607734</a>), In another family with CMT1F and in a sporadic patient with a similar phenotype, they found mutations in the same codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Perez-Olle, R., Jones, S. T., Liem, R. K. H. <strong>Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models.</strong> Hum. Molec. Genet. 13: 2207-2220, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15282209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15282209</a>] [<a href="https://doi.org/10.1093/hmg/ddh236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15282209">Perez-Olle et al. (2004)</a> demonstrated that the P8R mutation as well as 2 other mutations at this codon resulted in accumulation of the mutant NFL protein in the cell body and the proximal segments of neuronal processes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15282209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of an Austrian family with CMT2E, <a href="#21" class="mim-tip-reference" title="Miltenberger-Miltenyi, G., Janecke, A. R., Wanschitz, J. V., Timmerman, V., Windpassinger, C., Auer-Grumbach, M., Loscher, W. N. <strong>Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.</strong> Arch. Neurol. 64: 966-970, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620486</a>] [<a href="https://doi.org/10.1001/archneur.64.7.966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620486">Miltenberger-Miltenyi et al. (2007)</a> identified a heterozygous 23C-G transversion in the NEFL gene, resulting in a P8R substitution in the head domain of the protein. Disease onset was before age 15 years in all but 1 patient. The disorder was slowly progressive but resulted in a severe and disabling phenotype. Another unrelated patient with sporadic disease also had a P8R mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In cultured mouse motor neurons, <a href="#30" class="mim-tip-reference" title="Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W. <strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong> Hum. Molec. Genet. 16: 3103-3116, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881652</a>] [<a href="https://doi.org/10.1093/hmg/ddm272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881652">Zhai et al. (2007)</a> found that expression of Q333P (<a href="#0001">162280.0001</a>)- and P8R-mutant NEFL led to progressive degeneration and loss of neuronal viability. Degenerating motor neurons showed fragmentation and loss of neuritic processes associated with disruption of the neurofilament network and aggregation of the NEFL protein. Coexpression of mutant NEFL with wildtype HSPB1 (<a href="/entry/602195">602195</a>) diminished aggregation of mutant NEFL, induced reversal of mutant NEFL aggregates, and reduced mutant NEFL-induced loss of motor neuron viability. Similarly, expression of mutant HSPB1 (S135F; <a href="/entry/602195#0001">602195.0001</a>), which causes CMT2F (<a href="/entry/606595">606595</a>) also led to progressive degeneration of motor neurons with disruption of the neurofilament network and aggregation of NEFL protein. The 2 proteins were found to associate together, and the S135F-mutant HSPB1 had a dominant effect. <a href="#30" class="mim-tip-reference" title="Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W. <strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong> Hum. Molec. Genet. 16: 3103-3116, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881652</a>] [<a href="https://doi.org/10.1093/hmg/ddm272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881652">Zhai et al. (2007)</a> suggested that disruption of the neurofilament network with aggregation of NEFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs3832558 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3832558;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/rs3832558?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=rs3832558" 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=rs3832558" 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=RCV000015076 OR RCV000057123 OR RCV000481083 OR RCV001080241" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015076, RCV000057123, RCV000481083, RCV001080241" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015076...</a>
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<p>In a Bulgarian family in which 4 members over 3 generations had Charcot-Marie-Tooth disease type 1F (CMT1F; <a href="/entry/607734">607734</a>), <a href="#14" class="mim-tip-reference" title="Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J.-J., Butler, I. J., Mancias, P., Papasozomenos, S. C., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., Timmerman, V. <strong>Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.</strong> Brain 126: 590-597, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566280</a>] [<a href="https://doi.org/10.1093/brain/awg059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12566280">Jordanova et al. (2003)</a> identified a heterozygous 3-bp deletion (1581delGAG) in exon 4 of the NEFL gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#28" class="mim-tip-reference" title="Yamamoto, M., Yoshihara, T., Hattori, N., Sobue, G. <strong>Glu528del in NEFL is a polymorphic variant rather than a disease-causing mutation for Charcot-Marie-Tooth disease in Japan.</strong> Neurogenetics 5: 75-77, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14586770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14586770</a>] [<a href="https://doi.org/10.1007/s10048-003-0159-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14586770">Yamamoto et al. (2004)</a> presented evidence suggesting that the 3-bp deletion in the NEFL gene, which results in deletion of a glutamine at codon 528, is a polymorphic variant rather than a disease-causing mutation in Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14586770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs58640772 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58640772;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=rs58640772" 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=rs58640772" 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=RCV000015077 OR RCV000057141 OR RCV000790245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015077, RCV000057141, RCV000790245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015077...</a>
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<p>In a 71-year-old man with Charcot-Marie-Tooth disease type 2E (CMT2E; <a href="/entry/607684">607684</a>), <a href="#17" class="mim-tip-reference" title="Leung, C. L., Nagan, N., Graham, T. H., Liem, R. K. H. <strong>A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie-Tooth disease.</strong> Am. J. Med. Genet. 140A: 1021-1025, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16619203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16619203</a>] [<a href="https://doi.org/10.1002/ajmg.a.31242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16619203">Leung et al. (2006)</a> identified a heterozygous 13-bp duplication/insertion at nucleotide 61 in exon 1 of the NEFL gene, predicted to result in termination at codon 21. Transient transfection experiments showed that the mutated NEFL could not form filaments by itself, and in the presence of mutated NEFL, wildtype NEFL formed only short filaments and alpha-internexin (<a href="/entry/605338">605338</a>) filaments collapsed into aggregates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16619203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</strong>
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NEFL, LEU94PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs62636505 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636505;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=rs62636505" 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=rs62636505" 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=RCV000015078 OR RCV000057135" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015078, RCV000057135" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015078...</a>
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<p>In 4 affected members of a large Austrian family with Charcot-Marie-Tooth disease type 2E (CMT2E; <a href="/entry/607684">607684</a>), <a href="#21" class="mim-tip-reference" title="Miltenberger-Miltenyi, G., Janecke, A. R., Wanschitz, J. V., Timmerman, V., Windpassinger, C., Auer-Grumbach, M., Loscher, W. N. <strong>Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.</strong> Arch. Neurol. 64: 966-970, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620486</a>] [<a href="https://doi.org/10.1001/archneur.64.7.966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620486">Miltenberger-Miltenyi et al. (2007)</a> identified a heterozygous 281T-C transition in the NEFL gene, resulting in a leu94-to-pro (L94P) substitution in a highly conserved residue in the coil 1a domain. Disease onset was in the second decade of life with pes cavus, progressive plantar extensor weakness, and distal lower limb atrophy and weakness. Two patients became wheelchair-bound. Electrophysiologic studies showed intermediate motor nerve conduction velocities consistent with axonal pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</strong>
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NEFL, GLU140TER
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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> rs121913663 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913663;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/rs121913663?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=rs121913663" 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=rs121913663" 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=RCV000015079 OR RCV000057137" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015079, RCV000057137" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015079...</a>
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<p>In a Japanese man, born of consanguineous parents, with demyelinating Charcot-Marie-Tooth disease type 1F (CMT1F; <a href="/entry/607734">607734</a>), <a href="#1" class="mim-tip-reference" title="Abe, A., Numakura, C., Saito, K., Koide, H., Oka, N., Honma, A., Kishikawa, Y., Hayasaka, K. <strong>Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype.</strong> J. Hum. Genet. 54: 94-97, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19158810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19158810</a>] [<a href="https://doi.org/10.1038/jhg.2008.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19158810">Abe et al. (2009)</a> identified a homozygous 418G-T transversion in the NEFL gene, resulting in a glu140-to-ter (E140X) substitution. He had onset of gait problems before age 10 years, upper and lower limb muscle atrophy and weakness, distal sensory loss, waddling gait, and severely decreased motor nerve conduction velocity (13.8 m/s). A similarly affected brother needed a wheelchair by age 40, but neither parent was affected. <a href="#1" class="mim-tip-reference" title="Abe, A., Numakura, C., Saito, K., Koide, H., Oka, N., Honma, A., Kishikawa, Y., Hayasaka, K. <strong>Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype.</strong> J. Hum. Genet. 54: 94-97, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19158810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19158810</a>] [<a href="https://doi.org/10.1038/jhg.2008.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19158810">Abe et al. (2009)</a> postulated that the nonsense mutation would result in loss of function, in contrast to missense mutations which result in toxic gain of function, and concluded that homozygous nonsense mutations in the NEFL gene cause a recessive disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19158810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0008" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</strong>
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NEFL, GLU210TER
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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> rs199422214 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422214;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/rs199422214?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=rs199422214" 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=rs199422214" 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=RCV000022674" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022674" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022674</a>
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<p>In 4 Palestinian sibs with a severe, progressive peripheral neuropathy beginning in early childhood (CMT1F; <a href="/entry/607734">607734</a>), <a href="#29" class="mim-tip-reference" title="Yum, S. W., Zhang, J., Mo, K., Li, J., Scherer, S. S. <strong>A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy.</strong> Ann. Neurol. 66: 759-770, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20039262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20039262</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20039262[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20039262">Yum et al. (2009)</a> identified a homozygous 628G-T transversion in the NEFL gene, resulting in a glu210-to-ter (E210X) substitution. The unaffected consanguineous parents were heterozygous for the mutation. Visual evoked responses were prolonged in 3 of 4 children, suggesting the involvement of central nervous system axons. Sural nerve biopsy of 1 patient showed lack of immunostaining for NEFL, decreased numbers of myelinated axons, and some regenerating axons. Intermediate filaments were not present in remaining myelinated axons. In vitro functional expression studies showed that the mutant NEFL did not accumulate properly, suggesting an inability to form filaments or enhanced degradation, consistent with a loss of function. Although <a href="#29" class="mim-tip-reference" title="Yum, S. W., Zhang, J., Mo, K., Li, J., Scherer, S. S. <strong>A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy.</strong> Ann. Neurol. 66: 759-770, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20039262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20039262</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20039262[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20039262">Yum et al. (2009)</a> referred to this phenotype as an 'axonal' neuropathy, the median nerve conduction velocities in all affected patients ranged from 14 to 25 m/s, which is more consistent with a 'demyelinating' neuropathy, as in CMT1F. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20039262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0009" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0009 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</strong>
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NEFL, ARG421TER
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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> rs191346286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs191346286;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/rs191346286?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=rs191346286" 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=rs191346286" 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=RCV000172912 OR RCV001174357 OR RCV004821990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172912, RCV001174357, RCV004821990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172912...</a>
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<p>In a mother and her 3 sons with a variant of axonal Charcot-Marie-Tooth disease type 2E (CMT2E; <a href="/entry/607684">607684</a>) presenting as congenital myopathy, <a href="#3" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Marinakis, N. S., Schmitz-Abe, K., Ciarlini, P. D. S. C., Sargent, J. C., Markianos, K., De Girolami, U., Chad, D. A., Beggs, A. H. <strong>Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.</strong> JAMA Neurol. 71: 1413-1420, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25264603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25264603</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25264603[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/10.1001/jamaneurol.2014.1432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25264603">Agrawal et al. (2014)</a> identified a heterozygous c.1261C-T transition in the NEFL gene, resulting in an arg421-to-ter (R421X) substitution. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 139), 1000 Genomes Project, or Exome Sequencing Project databases. Analysis of patient cells showed that the mutation did not result in nonsense-mediated mRNA decay. Western blot analysis and immunofluorescent studies of patient muscle samples showed that the NEFL protein was present and localized properly to motor endplates at nerve terminals. Faint bands of full-length NEFL were found in muscle from 2 affected members and 2 controls; the presence of a truncated protein related to the R421X mutation could not be evaluated because of the low overall abundance of NEFL in skeletal muscle and a nonspecific or cross-reacting band at the molecular weight. <a href="#3" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Marinakis, N. S., Schmitz-Abe, K., Ciarlini, P. D. S. C., Sargent, J. C., Markianos, K., De Girolami, U., Chad, D. A., Beggs, A. H. <strong>Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.</strong> JAMA Neurol. 71: 1413-1420, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25264603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25264603</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25264603[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/10.1001/jamaneurol.2014.1432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25264603">Agrawal et al. (2014)</a> hypothesized that the translated truncated protein, which may be stable, could interfere with wildtype NEFL in mature neurofilament heteropolymers. The patients presented in infancy with hypotonia, delayed motor development, and distal muscle weakness; all became wheelchair-dependent at different ages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25264603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs62636503 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636503;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=rs62636503" 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=rs62636503" 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=RCV000057113 OR RCV000534161 OR RCV000585797 OR RCV001174356" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000057113, RCV000534161, RCV000585797, RCV001174356" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000057113...</a>
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<p>In 4 affected members of a 3-generation German family with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; <a href="/entry/617882">617882</a>), <a href="#32" class="mim-tip-reference" title="Zuchner, S., Vorgerd, M., Sindern, E., Schroder, J. M. <strong>The novel neurofilament light (NEFL) mutation glu397lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.</strong> Neuromusc. Disord. 14: 147-157, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14733962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14733962</a>] [<a href="https://doi.org/10.1016/j.nmd.2003.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14733962">Zuchner et al. (2004)</a> identified a heterozygous c.1189G-A transition in exon 3 of the NEFL gene, resulting in a glu397-to-lys (E397K) substitution at a conserved residue at the end of the rod domain. (<a href="#10" class="mim-tip-reference" title="Fabrizi, G. M., Cavallaro, T., Angiari, C., Cabrini, I., Taioli, F., Malerba, G., Bertolasi, L., Rizzuto, N. <strong>Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.</strong> Brain 130: 394-403, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17052987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17052987</a>] [<a href="https://doi.org/10.1093/brain/awl284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17052987">Fabrizi et al. (2007)</a> noted that the numbering of this mutation was changed to a c.1186G-A transition, resulting in a glu396-to-lys (E396K) substitution, based on an updated reference sequence.) The mutation, which was found by direct sequencing of the NEFL gene, segregated with the disorder in the family and was not found in 65 normal controls. Two asymptomatic family members also carried the mutation: they were 21 years of age, possibly suggesting age-related incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17052987+14733962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Fabrizi, G. M., Cavallaro, T., Angiari, C., Cabrini, I., Taioli, F., Malerba, G., Bertolasi, L., Rizzuto, N. <strong>Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.</strong> Brain 130: 394-403, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17052987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17052987</a>] [<a href="https://doi.org/10.1093/brain/awl284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17052987">Fabrizi et al. (2007)</a> identified heterozygosity for the E396K mutation in the NEFL gene in 2 Italian sibs (family E) with CMTDIG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17052987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Elbracht, M., Senderek, J., Schara, U., Nolte, K., Klopstock, T., Roos, A., Reimann, J., Zerres, K., Weis, J., Rudnik-Schoneborn, S. <strong>Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie-Tooth disease type 2E.</strong> Clin. Neuropath. 33: 335-343, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24887401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24887401</a>] [<a href="https://doi.org/10.5414/NP300742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24887401">Elbracht et al. (2014)</a> identified heterozygosity for the E396K mutation in the NEFL gene in 8 members of a multigenerational family with onset of CMTDIG since infancy or early childhood as well as in an unrelated patient (patient 9) with CMTDIG who had onset at age 50; he had no family history of CMT. The discrepancy in the phenotype among patients with the same mutation suggested additional genetic modifiers and broadened the phenotypic spectrum associated with this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24887401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 members of a Spanish family with CMTDIG, <a href="#4" class="mim-tip-reference" title="Berciano, J., Garcia, A., Peeters, K., Gallardo, E., De Vriendt, E., Palayo-Negro, A. L., Infante, J., Jordanova, A. <strong>NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.</strong> J. Neurol. 262: 1289-1300, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25877835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25877835</a>] [<a href="https://doi.org/10.1007/s00415-015-7709-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25877835">Berciano et al. (2015)</a> identified heterozygosity for the E396K mutation in the NEFL gene. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Variant Server databases, as well as 90 in-house genomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25877835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034136 OR RCV000057136 OR RCV000554079 OR RCV000585792 OR RCV000857201 OR RCV001027680 OR RCV001843465" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034136, RCV000057136, RCV000554079, RCV000585792, RCV000857201, RCV001027680, RCV001843465" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034136...</a>
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<p>In a mother and son with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; <a href="/entry/617882">617882</a>), <a href="#5" class="mim-tip-reference" title="Berciano, J., Peeters, K., Garcia, A., Lopez-Alburquerque, T., Gallardo, E., Hernandez-Fabian, A., Pelayo-Negro, A. L., De Vriendt, E., Infante, J., Jordanova, A. <strong>NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.</strong> J. Neurol. 263: 361-369, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26645395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26645395</a>] [<a href="https://doi.org/10.1007/s00415-015-7985-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26645395">Berciano et al. (2016)</a> identified a heterozygous c.293A-G transition in the NEFL gene, resulting in an asn98-to-ser (N98S) substitution at a conserved residue. The mutation was found by whole-exome sequencing after excluding mutations in several spinocerebellar ataxia and CMT genes. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26645395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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Abe, A., Numakura, C., Saito, K., Koide, H., Oka, N., Honma, A., Kishikawa, Y., Hayasaka, K.
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<strong>Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype.</strong>
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J. Hum. Genet. 54: 94-97, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19158810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19158810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19158810" 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/jhg.2008.13" target="_blank">Full Text</a>]
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<strong>Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth type 2E phenotype.</strong>
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Hum. Molec. Genet. 24: 2163-2174, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25552649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25552649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25552649[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=25552649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.</strong>
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JAMA Neurol. 71: 1413-1420, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25264603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25264603</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25264603[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=25264603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
|
|
|
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|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Berciano2015" class="mim-anchor"></a>
|
|
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|
|
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|
|
Berciano, J., Garcia, A., Peeters, K., Gallardo, E., De Vriendt, E., Palayo-Negro, A. L., Infante, J., Jordanova, A.
|
|
<strong>NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.</strong>
|
|
J. Neurol. 262: 1289-1300, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25877835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25877835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25877835" 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/s00415-015-7709-4" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
|
|
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|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Berciano2016" class="mim-anchor"></a>
|
|
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|
|
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|
|
Berciano, J., Peeters, K., Garcia, A., Lopez-Alburquerque, T., Gallardo, E., Hernandez-Fabian, A., Pelayo-Negro, A. L., De Vriendt, E., Infante, J., Jordanova, A.
|
|
<strong>NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.</strong>
|
|
J. Neurol. 263: 361-369, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26645395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26645395</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26645395" 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/s00415-015-7985-z" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Brownlees2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brownlees, J., Ackerley, S., Grierson, A. J., Jacobsen, N. J. O., Shea, K., Anderton, B. H., Leigh, P. N., Shaw, C. E., Miller, C. C. J.
|
|
<strong>Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport.</strong>
|
|
Hum. Molec. Genet. 11: 2837-2844, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1093/hmg/11.23.2837" target="_blank">Full Text</a>]
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="De Jonghe2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Jonghe, P., Mersiyanova, I., Nelis, E., Del Favero, J., Martin, J.-J., Van Broeckhoven, C., Evgrafov, O., Timmerman, V.
|
|
<strong>Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Ann. Neurol. 49: 245-249, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11220745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11220745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11220745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1531-8249(20010201)49:2<245::aid-ana45>3.0.co;2-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Elbracht2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elbracht, M., Senderek, J., Schara, U., Nolte, K., Klopstock, T., Roos, A., Reimann, J., Zerres, K., Weis, J., Rudnik-Schoneborn, S.
|
|
<strong>Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Clin. Neuropath. 33: 335-343, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24887401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24887401</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24887401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.5414/NP300742" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Fabrizi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fabrizi, G. M., Cavallaro, T., Angiari, C., Bertolasi, L., Cabrini, I., Ferrarini, M., Rizzuto, N.
|
|
<strong>Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Neurology 62: 1429-1431, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15111691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15111691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15111691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000120664.07186.3c" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Fabrizi2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fabrizi, G. M., Cavallaro, T., Angiari, C., Cabrini, I., Taioli, F., Malerba, G., Bertolasi, L., Rizzuto, N.
|
|
<strong>Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.</strong>
|
|
Brain 130: 394-403, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17052987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17052987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17052987" 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/brain/awl284" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Georgiou2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Georgiou, D.-M., Zidar, J., Korosec, M., Middleton, L. T., Kyriakides, T., Christodoulou, K.
|
|
<strong>A novel NF-L mutation pro22-to-ser is associated with CMT2 in a large Slovenian family.</strong>
|
|
Neurogenetics 4: 93-96, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12481988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12481988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12481988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-002-0138-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hirokawa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirokawa, N., Takeda, S.
|
|
<strong>Gene targeting studies begin to reveal the function of neurofilament proteins.</strong>
|
|
J. Cell Biol. 143: 1-4, 1998. Note: Erratum: J. Cell Biol. 143: 1142 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9763415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9763415</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9763415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.143.1.1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hurst1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hurst, J., Flavell, D., Julien, J.-P., Meijer, D., Mushynski, W., Grosveld, F.
|
|
<strong>The human neurofilament gene (NEFL) is located on the short arm of chromosome 8.</strong>
|
|
Cytogenet. Cell Genet. 45: 30-32, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3036423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3036423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3036423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Jordanova2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J.-J., Butler, I. J., Mancias, P., Papasozomenos, S. C., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., Timmerman, V.
|
|
<strong>Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.</strong>
|
|
Brain 126: 590-597, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566280" 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/brain/awg059" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Julien1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Julien, J.-P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., Mushynski, W.
|
|
<strong>The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.</strong>
|
|
Biochim. Biophys. Acta 909: 10-20, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3034332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3034332</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3034332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0167-4781(87)90041-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Lees1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lees, J. F., Shneidman, P. S., Skuntz, S. F., Carden, M. J., Lazzarini, R. A.
|
|
<strong>The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it.</strong>
|
|
EMBO J. 7: 1947-1955, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3138108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3138108</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3138108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03032.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Leung2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leung, C. L., Nagan, N., Graham, T. H., Liem, R. K. H.
|
|
<strong>A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie-Tooth disease.</strong>
|
|
Am. J. Med. Genet. 140A: 1021-1025, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16619203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16619203</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16619203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31242" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Levy1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Levy, E., Liem, R. K. H., D'Eustachio, P., Cowan, N. J.
|
|
<strong>Structure and evolutionary origin of the gene encoding NF-M, the middle-molecular-mass neurofilament protein.</strong>
|
|
Europ. J. Biochem. 166: 71-77, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3036526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3036526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3036526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1432-1033.1987.tb13485.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Lin2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, H., Zhai, J., Schlaepfer, W. W.
|
|
<strong>RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.</strong>
|
|
Hum. Molec. Genet. 14: 3643-3659, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236762" 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/ddi392" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Mersiyanova2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mersiyanova, I. V., Perepelov, A. V., Polyakov, A. V., Sitnikov, V. F., Dadali, E. L., Oparin, R. B., Petrin, A. N., Evgrafov, O. V.
|
|
<strong>A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene.</strong>
|
|
Am. J. Hum. Genet. 67: 37-46, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10841809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10841809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10841809[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=10841809" 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/10.1086/302962" target="_blank">Full Text</a>]
|
|
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|
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|
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|
|
|
|
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|
|
<a id="21" class="mim-anchor"></a>
|
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|
|
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|
|
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|
|
Miltenberger-Miltenyi, G., Janecke, A. R., Wanschitz, J. V., Timmerman, V., Windpassinger, C., Auer-Grumbach, M., Loscher, W. N.
|
|
<strong>Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.</strong>
|
|
Arch. Neurol. 64: 966-970, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620486" 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/10.1001/archneur.64.7.966" target="_blank">Full Text</a>]
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Nguyen2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nguyen, M. D., Lariviere, R. C., Julien, J.-P.
|
|
<strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong>
|
|
Neuron 30: 135-147, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1016/s0896-6273(01)00268-9" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
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|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Perez-Olle2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Perez-Olle, R., Jones, S. T., Liem, R. K. H.
|
|
<strong>Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models.</strong>
|
|
Hum. Molec. Genet. 13: 2207-2220, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15282209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15282209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15282209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh236" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
|
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|
|
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|
Previtali, S. C., Zerega, B., Sherman, D. L., Brophy, P. J., Dina, G., King, R. H. M., Salih, M. M., Feltri, L., Quattrini, A., Ravazzolo, R., Wrabetz, L., Monaco, A. P., Bolino, A.
|
|
<strong>Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve.</strong>
|
|
Hum. Molec. Genet. 12: 1713-1723, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837694</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg179" target="_blank">Full Text</a>]
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|
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|
|
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|
|
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|
|
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|
|
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|
|
Rebelo, A. P., Abrams, A. J., Cottenie, E., Horga, A., Gonzalez, M., Bis, D. M., Sanchez-Mejias, A., Pinto, M., Buglo, E., Markel, K., Prince, J., Laura, M., and 10 others.
|
|
<strong>Cryptic amyloidogenic elements in the 3-prime UTRs of neurofilament genes trigger axonal neuropathy.</strong>
|
|
Am. J. Hum. Genet. 98: 597-614, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27040688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27040688</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27040688[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=27040688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2016.02.022" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Sasaki, T., Gotow, T., Shiozaki, M., Sakaue, F., Saito, T., Julien, J.-P., Uchiyama, Y., Hisanaga, S.
|
|
<strong>Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie-Tooth disease mutants.</strong>
|
|
Hum. Molec. Genet. 15: 943-952, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16452125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16452125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16452125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl011" target="_blank">Full Text</a>]
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|
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|
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|
|
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|
|
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|
|
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|
|
Somerville, M. J., McLachlan, D. R., Percy, M. E.
|
|
<strong>Localization of the 68000-Da human neurofilament gene (NF68) using a murine cDNA probe.</strong>
|
|
Genome 30: 499-500, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3145240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3145240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3145240" 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/10.1139/g88-083" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
<li>
|
|
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|
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|
|
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|
|
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|
|
Yamamoto, M., Yoshihara, T., Hattori, N., Sobue, G.
|
|
<strong>Glu528del in NEFL is a polymorphic variant rather than a disease-causing mutation for Charcot-Marie-Tooth disease in Japan.</strong>
|
|
Neurogenetics 5: 75-77, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14586770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14586770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14586770" 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/s10048-003-0159-7" target="_blank">Full Text</a>]
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|
|
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|
|
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|
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Yum, S. W., Zhang, J., Mo, K., Li, J., Scherer, S. S.
|
|
<strong>A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy.</strong>
|
|
Ann. Neurol. 66: 759-770, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20039262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20039262</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20039262[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=20039262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.21728" target="_blank">Full Text</a>]
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|
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|
|
|
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|
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|
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|
|
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|
|
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|
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Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W.
|
|
<strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong>
|
|
Hum. Molec. Genet. 16: 3103-3116, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddm272" target="_blank">Full Text</a>]
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|
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|
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Zhu, Q., Couillard-Despres, S., Julien, J.-P.
|
|
<strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong>
|
|
Exp. Neurol. 148: 299-316, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398473" 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/10.1006/exnr.1997.6654" target="_blank">Full Text</a>]
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<strong>The novel neurofilament light (NEFL) mutation glu397lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.</strong>
|
|
Neuromusc. Disord. 14: 147-157, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14733962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14733962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14733962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Alan F. Scott - updated : 01/07/2022
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Cassandra L. Kniffin - updated : 02/21/2018<br>Cassandra L. Kniffin - updated : 4/27/2016<br>Cassandra L. Kniffin - updated : 6/10/2015<br>Cassandra L. Kniffin - updated : 8/30/2010<br>Cassandra L. Kniffin - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 6/22/2009<br>George E. Tiller - updated : 4/23/2009<br>Cassandra L. Kniffin - updated : 4/1/2008<br>George E. Tiller - updated : 4/5/2007<br>Marla J. F. O'Neill - updated : 5/25/2006<br>George E. Tiller - updated : 5/4/2005<br>Cassandra L. Kniffin - updated : 1/25/2005<br>George E. Tiller - updated : 4/1/2004<br>Cassandra L. Kniffin - updated : 3/17/2004<br>Cassandra L. Kniffin - updated : 5/1/2003<br>Cassandra L. Kniffin - updated : 4/30/2003<br>Victor A. McKusick - updated : 1/8/2003<br>Dawn Watkins-Chow - updated : 11/5/2002<br>Victor A. McKusick - updated : 9/6/2000
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Victor A. McKusick : 8/28/1987
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carol : 04/07/2023<br>mgross : 01/11/2022<br>mgross : 01/07/2022<br>carol : 03/06/2018<br>ckniffin : 02/21/2018<br>carol : 04/28/2016<br>ckniffin : 4/27/2016<br>alopez : 6/11/2015<br>mcolton : 6/11/2015<br>ckniffin : 6/10/2015<br>terry : 3/14/2013<br>wwang : 9/10/2010<br>ckniffin : 8/30/2010<br>wwang : 11/4/2009<br>ckniffin : 10/30/2009<br>wwang : 9/10/2009<br>ckniffin : 9/2/2009<br>wwang : 6/29/2009<br>ckniffin : 6/22/2009<br>wwang : 5/19/2009<br>terry : 4/23/2009<br>carol : 2/13/2009<br>wwang : 4/3/2008<br>ckniffin : 4/1/2008<br>alopez : 4/13/2007<br>terry : 4/5/2007<br>wwang : 6/1/2006<br>terry : 5/25/2006<br>terry : 2/3/2006<br>tkritzer : 5/4/2005<br>ckniffin : 1/25/2005<br>tkritzer : 4/8/2004<br>terry : 4/1/2004<br>terry : 4/1/2004<br>tkritzer : 3/17/2004<br>ckniffin : 3/17/2004<br>carol : 5/12/2003<br>ckniffin : 5/1/2003<br>ckniffin : 4/30/2003<br>carol : 4/29/2003<br>ckniffin : 4/23/2003<br>carol : 1/14/2003<br>carol : 1/14/2003<br>tkritzer : 1/10/2003<br>terry : 1/8/2003<br>carol : 11/7/2002<br>tkritzer : 11/5/2002<br>tkritzer : 11/5/2002<br>tkritzer : 11/5/2002<br>alopez : 3/26/2001<br>carol : 9/15/2000<br>terry : 9/6/2000<br>psherman : 3/27/1998<br>carol : 8/31/1992<br>supermim : 3/16/1992<br>carol : 1/15/1991<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>carol : 2/14/1989
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</span>
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</div>
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<div class="container visible-print-block">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 162280
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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NEUROFILAMENT PROTEIN, LIGHT POLYPEPTIDE; NEFL
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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NEUROFILAMENT PROTEIN, LIGHT CHAIN; NFL<br />
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NF68
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</span>
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</h4>
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</div>
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<br />
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</div>
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<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: NEFL</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 717012004, 719980006;
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 8p21.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 8:24,950,955-24,956,612 </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="3">
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<span class="mim-font">
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8p21.2
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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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Charcot-Marie-Tooth disease, dominant intermediate G
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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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617882
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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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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Charcot-Marie-Tooth disease, type 1F
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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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607734
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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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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Charcot-Marie-Tooth disease, type 2E
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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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607684
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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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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</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">
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<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">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The NEFL gene encodes the neurofilament light polypeptide, a subunit that forms type IV intermediate filament heteropolymers, which are a major component of the neuronal cytoskeleton (summary by Agrawal et al., 2014). </p><p>Cytoplasmic intermediate filaments (IF) can be divided into 5 subclasses based on their biochemical properties, immunologic specificity and tissue distribution: keratin (139350, 148030) filaments in epithelial cells, vimentin (193060) filaments in cells of mesenchymal origin, desmin (125660) in muscle cells, glial filaments in astrocytes, and neurofilaments in neurons. The different types of intermediate filament proteins share common structural features. Neurofilaments are composed of 3 neuron-specific proteins with apparent molecular masses of 68 kD (NFL), 125 kD (NFM), and 200 kD (NFH) on SDS-gel electrophoresis (summary by Julien et al., 1987). </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>Julien et al. (1987) isolated the genomic copy of the human NFL gene using an NFL cDNA probe. After transfection into mouse L-cells, the cloned gene was transcribed into 2 mRNAs approximately 2.6 and 4.3 kb long. The different sequence data show that the intermediate filament proteins contain a similar alpha-helical domain of conserved length capable of forming coiled-coils. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The vimentin, desmin, and glial fibrillary acidic protein genes each contains 8 introns at identical positions, 6 of the introns being located within the regions encoding alpha-helical sequences. A majority of the introns in the less closely related keratin genes occurred at similar or identical positions. The NFL gene was found by Julien et al. (1987) to have an unexpected intron-exon organization in that it entirely lacks introns at positions found in other members of the intermediate filament gene family. It contains only 3 introns. Possible evolutionary explanations were discussed. Lees et al. (1988) analyzed the structure of the NFH subunit. They concluded that divergence of the neural IF lineage from the nonneural IF lineage probably involved ancestral IF gene duplication rather than RNA-mediated transposition. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By Southern blot analysis of DNA from hybrid cell panels and by in situ hybridization, Hurst et al. (1987) assigned the NEFL gene to 8p21. Somerville et al. (1988) also assigned this gene, which they symbolized NF68, to 8p21 by in situ hybridization. In addition, they found secondary hybridization sites at the centromeric region of chromosome 2 and on the long arm of chromosome 7, which are putative loci for other intermediate filaments. The corresponding gene for NFL, as well as that for middle-molecular-mass neurofilament protein, appears to be on chromosome 14 in the mouse (Levy et al., 1987). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Previtali et al. (2003) detected MTMR2 (603557) in all cytoplasmic compartments of myelin-forming Schwann cells, as well as in the cytoplasm of non-myelin-forming Schwann cells and both sensory and motor neurons. In contrast, MTMR2 was detected in the nucleus of Schwann cells and motor neurons, but not in the nucleus of sensory neurons. NFL interacted with MTMR2 in yeast 2-hybrid screenings using both fetal brain and peripheral nerve libraries and was found to interact with MTMR2 in both Schwann cells and neurons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Charcot-Marie-Tooth Disease Type 2E</em></strong></p><p>
|
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In a large Russian family with an axonal form of Charcot-Marie-Tooth disease (CMT2E; 607684), Mersiyanova et al. (2000) identified a gln333-to-pro mutation in the NEFL gene (Q333P; 162280.0001). </p><p>Using a transient expression system, Brownlees et al. (2002) demonstrated that the pro8-to-arg (P8R; 162280.0003) and Q333P (162280.0001) mutant NEFL proteins, which cause CMT2E, disrupted both neurofilament assembly and axonal transport of neurofilaments in cultured mammalian cells and neurons. CMT mutant neurofilaments also perturbed the localization of mitochondria in neurons. Accumulations of neurofilaments are a pathologic feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS; 105400), Alzheimer disease (104300), Parkinson disease (168600), dementia with Lewy bodies (127750), and diabetic neuropathy (see 603933). The authors concluded that their results demonstrated that aberrant neurofilament assembly and transport can induce neurologic disease and further implicated defective neurofilament metabolism in the pathogenesis of human neurodegenerative diseases. </p><p><strong><em>Charcot-Marie-Tooth Disease Type 1F</em></strong></p><p>
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Jordanova et al. (2003) identified 6 missense mutations and a 3-bp deletion (162280.0004) in the NEFL gene in patients with autosomal dominant demyelinating CMT1F (607734). Three of these mutations occurred in codon 8 (see, e.g., 162280.0003). Yamamoto et al. (2004) presented evidence suggesting that the 3-bp deletion in the NEFL gene is a polymorphic variant rather than a disease-causing mutation in Japan. </p><p><strong><em>Charcot-Marie-Tooth Disease, Dominant Intermediate G</em></strong></p><p>
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In 4 affected members of a 3-generation German family with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; 617882). Zuchner et al. (2004) identified a heterozygous missense mutation in the NEFL gene (E396K; 162280.0010). The mutation, which was found by direct sequencing of the NEFL gene, segregated with the disorder in the family. Two asymptomatic family members also carried the mutation: they were 21 years of age, possibly suggesting age-related incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. </p><p>Elbracht et al. (2014) identified heterozygosity for the E396K mutation in the NEFL gene in 8 members of a multigenerational family with onset of CMTDIG since infancy or early childhood as well as in an unrelated patient (patient 9) with CMTDIG who had onset at age 50; he had no family history of CMT. The discrepancy in the phenotype among patients with the same mutation suggested additional genetic modifiers and broadened the phenotypic spectrum associated with this mutation. Functional studies of the variant were not performed. </p><p>Berciano et al. (2015) identified heterozygosity for the E396K mutation in the NEFL gene in 4 affected members of a Spanish family with CMTDIG. The variant, which was found by exome sequencing of candidate disease genes, was confirmed by Sanger sequencing and segregated with the disorder. Functional studies of the variant and studies of patient cells were not performed. </p><p>In a Spanish woman and her son with CMTDIG, Berciano et al. (2016) identified a heterozygous missense mutation in the NEFL gene (N98S; 162280.0011). The mutation was found by exome sequencing. Functional studies of the variant were not performed. </p><p><strong><em>NEFL Aggregation Studies</em></strong></p><p>
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Lin et al. (2005) reported that p190RhoGEF (612790), an RNA-binding protein that binds to a destabilizing element in NEFL mRNA, is involved in aggregation of NEFL protein and is implicated in the pathogenesis of motor neuron degeneration. The 190RhoGEF protein coaggregated with unassembled NEFL protein, and that coaggregation was associated with downregulation of parent NEFL mRNA in neuronal cells. Coexpression of medium neurofilament (NFM; 162250) increased NF assembly and reduced RNA-triggered aggregation as well as loss of solubility of NEFL protein. siRNA-induced downregulation of p190RhoGEF not only reduced aggregation and promoted assembly of NEFL and NFM, but also caused reversal of aggregation and recovery of NF assembly in transfected cells. Examination of transgenic models of motor neuron disease showed that prominent aggregates of p190RhoGEF and NEFL and downregulation of NEFL expression occurred in degenerating motor neurons of mice expressing untranslated NEFL RNA or a G93A-mutant SOD1 (147450) transgene. Moreover, aggregates of p190RhoGEF and NEFL appeared as early pathologic changes in presymptomatic G93A-mutant SOD1 transgenic mice. Lin et al. (2005) concluded that p190RhoGEF is involved in aggregation of NEFL protein and proposed that aggregation of p190RhoGEF and NEFL may be an upstream event triggering neurotoxicity in motor neuron disease. </p><p>Rebelo et al. (2016) identified NEFL as a gene with the potential to cause abnormal and toxic protein aggregations as a result of a stop-loss mutation, i.e., a mutation that extends the 3-prime translation frame beyond the normal stop codon, resulting in the addition of cryptic amyloidogenic elements (CAE). Cultured neuronal cells expressing such frameshift NEFL mutations showed prominent toxic protein aggregations in the cytoplasm as well as rounded cells and a lack of axon-like projections, indicating that they would be pathogenic and thus could likely result in neurologic disorders. Similar findings were observed for frameshift mutations in the NEFH gene (162230). </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>Genotype/Phenotype Correlations</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>Perez-Olle et al. (2004) analyzed the effects of 5 NFL mutations on the assembly and intracellular distribution of intermediate filaments (IFs), and compared the results with those obtained previously for other NFL mutations. Although all NFL mutants affected the formation of IF networks, there were differential effects on the assembly of IFs depending on the mutation. Defective transport of the mutant NFL subunits was observed for all the CMT-linked NFL mutations, but the characteristics of this defect also depended on the specific mutation. The authors concluded that defects in the assembly and transport of NFs are common to all NFL mutants studied to that time, but the exact nature of the defect appeared to be correlated with each mutant genotype. </p><p>In a review of published studies of patients with NEFL mutations, Miltenberger-Miltenyi et al. (2007) concluded that there are no obvious genotype/phenotype correlations. However, the authors noted that mutations in the head domain of NEFL may cause more severe slowing of nerve conduction velocities than mutations in the coil 2B domain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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">
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<p>Using homologous recombination in embryonic stem cells, Zhu et al. (1997) generated mice bearing a targeted disruption of the NFL gene. The absence of NFL protein resulted in dramatic reduction in the levels of Nfm and Nfh proteins in the brain and sciatic nerve, while increases for other cytoskeletal proteins, such as tubulin and GAP43 (162060), were detected. Despite a lack of neurofilaments and hypotrophy of axons, the NFL knockout mice developed normally and did not exhibit any overt phenotypes. However, in both heterozygous and homozygous NFL mutant mice, Zhu et al. (1997) observed a reduction in the normal regeneration of myelinated axons following crush injury of peripheral nerves. Using electron microscopy of nerve segments distal to the crush site, Zhu et al. (1997) detected abundant clusters of axonal sprouts that were indicative of retarded maturation of regenerating fibers in NFL null mice. Long-term analysis indicated that neurofilament-deficient axons have the capacity to regrow and to remyelinate, albeit at a slower rate. Zhu et al. (1997) concluded that neurofilaments play a role in the maturation of regenerating myelinated axons. </p><p>Hirokawa and Takeda (1998) reviewed contributions gene targeting studies had made to understanding the role of each of the neurofilament component proteins in neurofilament formation and in determination of the axonal caliber. </p><p>Using immunohistochemistry and immunoblots experiments, Nguyen et al. (2001) detected a hyperphosphorylation of neurofilament proteins associated with abnormally elevated p25/p35 (see 603460) ratio and Cdk5 (123831) activity in the spinal cord of transgenic mice with a gly37-to-arg (G37R) mutation in the SOD1 gene (147450.0001), a mouse model of amyotrophic lateral sclerosis (ALS; 105400). Nguyen et al. (2001) bred the Sod1 mutant transgene onto neurofilament mutant backgrounds and observed that the absence of NFL provoked an accumulation of unassembled neurofilament subunits in the perikaryon of motor neurons. Using double immunofluorescence microscopy, Nguyen et al. (2001) confirmed that Cdk5 and p25 colocalize with perikaryal neurofilament accumulations in SOD1(G37R) mice on the neurofilament mutant background. Immunoblotting showed that the occurrence of perikaryal neurofilament accumulations in SOD1(G37R) mice was associated with a reduction in the phosphorylation of microtubule-associated protein tau (157140), another p25/Cdk5 substrate. The absence of the NFL subunit extended the average life span of SOD1(G37R) mice. Nguyen et al. (2001) hypothesized that perikaryal accumulations of neurofilament proteins in motor neurons may alleviate ALS pathogenesis in Sod1 mutant mice by acting as a phosphorylation sink for Cdk5 activity, thereby reducing the detrimental hyperphosphorylation of tau and other neuronal substrates. </p><p>Adebola et al. (2015) found that knockin mice heterozygous or homozygous for the Nefl P8R (162280.0003) mutation were behaviorally similar to wildtype animals. The authors attributed the lack of phenotype to possible background modifier genes. In contrast, knockin mice heterozygous for the Nefl N98S (162280.0011) mutation developed tremor and a hindlimb clasping phenotype as early as 1 month of age. Abnormal neuronal processes in the cerebral cortex and pons were present as soon as 7 days after birth, and these animals had multiple inclusions in cell bodies and proximal axons of spinal cord neurons. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>11 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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NEFL, GLN333PRO
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<br />
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SNP: rs59443585,
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ClinVar: RCV000015072, RCV000057151
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<p>In a large Mordovian (Russian) family with autosomal dominant Charcot-Marie-Tooth disease of the axonal form (CMT2E; 607684), Mersiyanova et al. (2000) found linkage to chromosome 8p21 and identified a 998A-C transversion in the first exon of the NEFL gene, resulting in a gln333-to-pro (Q333P) mutation in a conserved region. This alteration was not found in 180 normal chromosomes. No mutations in this gene were found in 20 unrelated CMT2 patients or in 26 others with an undetermined form of CMT. The authors suggested the designation CMT2E for this disorder. </p><p>In cultured mouse motor neurons, Zhai et al. (2007) found that expression of Q333P- and P8R (162280.0003)-mutant NEFL led to progressive degeneration and loss of neuronal viability. Degenerating motor neurons showed fragmentation and loss of neuritic processes associated with disruption of the neurofilament network and aggregation of the NEFL protein. Coexpression of mutant NEFL with wildtype HSPB1 (602195) diminished aggregation of mutant NEFL, induced reversal of mutant NEFL aggregates, and reduced mutant NEFL-induced loss of motor neuron viability. Similarly, expression of mutant HSPB1 (S135F; 602195.0001), which causes CMT2F (606595) also led to progressive degeneration of motor neurons with disruption of the neurofilament network and aggregation of NEFL protein. The 2 proteins were found to associate together, and the S135F-mutant HSPB1 had a dominant effect. Zhai et al. (2007) suggested that disruption of the neurofilament network with aggregation of NEFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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NEFL, PRO22SER
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<br />
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SNP: rs28928910,
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ClinVar: RCV000015073, RCV000057144, RCV000194357, RCV000414916, RCV000415401, RCV001196666, RCV002362585
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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>Georgiou et al. (2002) described a large 5-generation Slovenian family with autosomal dominant Charcot-Marie-Tooth disease type 2E (CMT2E; 607684) in which all 10 affected members had a 64C-T transition in exon 1 of the NEFL gene resulting in a pro22-to-ser (P22S) substitution. Disease onset in most patients was in the first decade of life. The presenting symptoms were difficulty in walking or running, due to a slowly progressive distal weakness and wasting of the lower limbs. A steppage gait, pes cavus, and hammertoes were typically present. Over a period of 20 years after disease onset, two-thirds of patients developed upper limb involvement resulting in claw hands. All patients were ambulatory 20 to 30 years after onset. </p><p>Fabrizi et al. (2004) identified the P22S mutation in affected members of an Italian family with CMT2E. Sural nerve biopsy showed loss of large myelinated axons and a few swollen axons encased in a thin myelin sheath. Neurofilaments were grouped in a random orientation. </p><p>Sasaki et al. (2006) noted that the P22S mutation abolishes a phosphorylation sequence in the head domain of NEFL. In vitro functional expression studies in isolated human cells and in rat cortical neuron cultures showed that the mutant P22S or P22T NEFL proteins formed large aggregates and assembled into short twisty threads thinner than 10 nm filaments. Those threads associated with each other at their ends and entangled into large aggregates. The structure disturbance occurred during oligomer formation. Further studies showed that the pro22 mutations abolished phosphorylation of residue thr21 by CDK5 (123831), which normally suppresses filament assembly. However, the mutant proteins were able to be phosphorylated by protein kinase A to the same extent as wildtype, which inhibited aggregate formation in cortical neurons. The results indicated that the pro22 CMT mutation induces abnormal filament aggregates by disrupting proper oligomer formation, but demonstrated that the formation of these aggregates could be mitigated by phosphorylation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NEFL, PRO8ARG
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<br />
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SNP: rs60261494, rs61491953,
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ClinVar: RCV000015074, RCV000015075, RCV000057129
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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 members of a Belgian family with Charcot-Marie-Tooth disease type 2E (CMT2E; 607684), De Jonghe et al. (2001) demonstrated a double transition at nucleotides 22 to 23 (CC to AG) in exon 1 of the NEFL gene, resulting in a pro8-to-arg (P8R) substitution. The patients presented with a classic but rather severe CMT phenotype with onset in the second decade. Nerve conduction velocities were sometimes severely slowed. </p><p>Jordanova et al. (2003) found the P8R mutation in affected members of a family segregating CMT1F (607734), In another family with CMT1F and in a sporadic patient with a similar phenotype, they found mutations in the same codon. </p><p>Perez-Olle et al. (2004) demonstrated that the P8R mutation as well as 2 other mutations at this codon resulted in accumulation of the mutant NFL protein in the cell body and the proximal segments of neuronal processes. </p><p>In affected members of an Austrian family with CMT2E, Miltenberger-Miltenyi et al. (2007) identified a heterozygous 23C-G transversion in the NEFL gene, resulting in a P8R substitution in the head domain of the protein. Disease onset was before age 15 years in all but 1 patient. The disorder was slowly progressive but resulted in a severe and disabling phenotype. Another unrelated patient with sporadic disease also had a P8R mutation. </p><p>In cultured mouse motor neurons, Zhai et al. (2007) found that expression of Q333P (162280.0001)- and P8R-mutant NEFL led to progressive degeneration and loss of neuronal viability. Degenerating motor neurons showed fragmentation and loss of neuritic processes associated with disruption of the neurofilament network and aggregation of the NEFL protein. Coexpression of mutant NEFL with wildtype HSPB1 (602195) diminished aggregation of mutant NEFL, induced reversal of mutant NEFL aggregates, and reduced mutant NEFL-induced loss of motor neuron viability. Similarly, expression of mutant HSPB1 (S135F; 602195.0001), which causes CMT2F (606595) also led to progressive degeneration of motor neurons with disruption of the neurofilament network and aggregation of NEFL protein. The 2 proteins were found to associate together, and the S135F-mutant HSPB1 had a dominant effect. Zhai et al. (2007) suggested that disruption of the neurofilament network with aggregation of NEFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</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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NEFL, 3-BP DEL, 1581GAG
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<br />
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SNP: rs3832558,
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gnomAD: rs3832558,
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ClinVar: RCV000015076, RCV000057123, RCV000481083, RCV001080241
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Bulgarian family in which 4 members over 3 generations had Charcot-Marie-Tooth disease type 1F (CMT1F; 607734), Jordanova et al. (2003) identified a heterozygous 3-bp deletion (1581delGAG) in exon 4 of the NEFL gene. </p><p>Yamamoto et al. (2004) presented evidence suggesting that the 3-bp deletion in the NEFL gene, which results in deletion of a glutamine at codon 528, is a polymorphic variant rather than a disease-causing mutation in Japan. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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NEFL, 13-BP DUP/INS, NT61
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<br />
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SNP: rs58640772,
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ClinVar: RCV000015077, RCV000057141, RCV000790245
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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 71-year-old man with Charcot-Marie-Tooth disease type 2E (CMT2E; 607684), Leung et al. (2006) identified a heterozygous 13-bp duplication/insertion at nucleotide 61 in exon 1 of the NEFL gene, predicted to result in termination at codon 21. Transient transfection experiments showed that the mutated NEFL could not form filaments by itself, and in the presence of mutated NEFL, wildtype NEFL formed only short filaments and alpha-internexin (605338) filaments collapsed into aggregates. </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>.0006 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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NEFL, LEU94PRO
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<br />
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SNP: rs62636505,
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ClinVar: RCV000015078, RCV000057135
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 4 affected members of a large Austrian family with Charcot-Marie-Tooth disease type 2E (CMT2E; 607684), Miltenberger-Miltenyi et al. (2007) identified a heterozygous 281T-C transition in the NEFL gene, resulting in a leu94-to-pro (L94P) substitution in a highly conserved residue in the coil 1a domain. Disease onset was in the second decade of life with pes cavus, progressive plantar extensor weakness, and distal lower limb atrophy and weakness. Two patients became wheelchair-bound. Electrophysiologic studies showed intermediate motor nerve conduction velocities consistent with axonal pathology. </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>.0007 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</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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NEFL, GLU140TER
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<br />
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SNP: rs121913663,
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gnomAD: rs121913663,
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ClinVar: RCV000015079, RCV000057137
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Japanese man, born of consanguineous parents, with demyelinating Charcot-Marie-Tooth disease type 1F (CMT1F; 607734), Abe et al. (2009) identified a homozygous 418G-T transversion in the NEFL gene, resulting in a glu140-to-ter (E140X) substitution. He had onset of gait problems before age 10 years, upper and lower limb muscle atrophy and weakness, distal sensory loss, waddling gait, and severely decreased motor nerve conduction velocity (13.8 m/s). A similarly affected brother needed a wheelchair by age 40, but neither parent was affected. Abe et al. (2009) postulated that the nonsense mutation would result in loss of function, in contrast to missense mutations which result in toxic gain of function, and concluded that homozygous nonsense mutations in the NEFL gene cause a recessive disorder. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1F</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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NEFL, GLU210TER
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<br />
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SNP: rs199422214,
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gnomAD: rs199422214,
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ClinVar: RCV000022674
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 Palestinian sibs with a severe, progressive peripheral neuropathy beginning in early childhood (CMT1F; 607734), Yum et al. (2009) identified a homozygous 628G-T transversion in the NEFL gene, resulting in a glu210-to-ter (E210X) substitution. The unaffected consanguineous parents were heterozygous for the mutation. Visual evoked responses were prolonged in 3 of 4 children, suggesting the involvement of central nervous system axons. Sural nerve biopsy of 1 patient showed lack of immunostaining for NEFL, decreased numbers of myelinated axons, and some regenerating axons. Intermediate filaments were not present in remaining myelinated axons. In vitro functional expression studies showed that the mutant NEFL did not accumulate properly, suggesting an inability to form filaments or enhanced degradation, consistent with a loss of function. Although Yum et al. (2009) referred to this phenotype as an 'axonal' neuropathy, the median nerve conduction velocities in all affected patients ranged from 14 to 25 m/s, which is more consistent with a 'demyelinating' neuropathy, as in CMT1F. </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>.0009 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2E</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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NEFL, ARG421TER
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<br />
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SNP: rs191346286,
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gnomAD: rs191346286,
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ClinVar: RCV000172912, RCV001174357, RCV004821990
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a mother and her 3 sons with a variant of axonal Charcot-Marie-Tooth disease type 2E (CMT2E; 607684) presenting as congenital myopathy, Agrawal et al. (2014) identified a heterozygous c.1261C-T transition in the NEFL gene, resulting in an arg421-to-ter (R421X) substitution. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 139), 1000 Genomes Project, or Exome Sequencing Project databases. Analysis of patient cells showed that the mutation did not result in nonsense-mediated mRNA decay. Western blot analysis and immunofluorescent studies of patient muscle samples showed that the NEFL protein was present and localized properly to motor endplates at nerve terminals. Faint bands of full-length NEFL were found in muscle from 2 affected members and 2 controls; the presence of a truncated protein related to the R421X mutation could not be evaluated because of the low overall abundance of NEFL in skeletal muscle and a nonspecific or cross-reacting band at the molecular weight. Agrawal et al. (2014) hypothesized that the translated truncated protein, which may be stable, could interfere with wildtype NEFL in mature neurofilament heteropolymers. The patients presented in infancy with hypotonia, delayed motor development, and distal muscle weakness; all became wheelchair-dependent at different ages. </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>.0010 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE G</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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NEFL, GLU396LYS ({dbSNP rs62636503})
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<br />
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SNP: rs62636503,
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ClinVar: RCV000057113, RCV000534161, RCV000585797, RCV001174356
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 affected members of a 3-generation German family with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; 617882), Zuchner et al. (2004) identified a heterozygous c.1189G-A transition in exon 3 of the NEFL gene, resulting in a glu397-to-lys (E397K) substitution at a conserved residue at the end of the rod domain. (Fabrizi et al. (2007) noted that the numbering of this mutation was changed to a c.1186G-A transition, resulting in a glu396-to-lys (E396K) substitution, based on an updated reference sequence.) The mutation, which was found by direct sequencing of the NEFL gene, segregated with the disorder in the family and was not found in 65 normal controls. Two asymptomatic family members also carried the mutation: they were 21 years of age, possibly suggesting age-related incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. </p><p>Fabrizi et al. (2007) identified heterozygosity for the E396K mutation in the NEFL gene in 2 Italian sibs (family E) with CMTDIG. </p><p>Elbracht et al. (2014) identified heterozygosity for the E396K mutation in the NEFL gene in 8 members of a multigenerational family with onset of CMTDIG since infancy or early childhood as well as in an unrelated patient (patient 9) with CMTDIG who had onset at age 50; he had no family history of CMT. The discrepancy in the phenotype among patients with the same mutation suggested additional genetic modifiers and broadened the phenotypic spectrum associated with this mutation. </p><p>In 4 members of a Spanish family with CMTDIG, Berciano et al. (2015) identified heterozygosity for the E396K mutation in the NEFL gene. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Variant Server databases, as well as 90 in-house genomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE G</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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NEFL, ASN98SER ({dbSNP rs58982919})
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<br />
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SNP: rs58982919,
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ClinVar: RCV000034136, RCV000057136, RCV000554079, RCV000585792, RCV000857201, RCV001027680, RCV001843465
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a mother and son with dominant intermediate Charcot-Marie-Tooth disease G (CMTDIG; 617882), Berciano et al. (2016) identified a heterozygous c.293A-G transition in the NEFL gene, resulting in an asn98-to-ser (N98S) substitution at a conserved residue. The mutation was found by whole-exome sequencing after excluding mutations in several spinocerebellar ataxia and CMT genes. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Abe, A., Numakura, C., Saito, K., Koide, H., Oka, N., Honma, A., Kishikawa, Y., Hayasaka, K.
|
|
<strong>Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype.</strong>
|
|
J. Hum. Genet. 54: 94-97, 2009.
|
|
|
|
|
|
[PubMed: 19158810]
|
|
|
|
|
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[Full Text: https://doi.org/10.1038/jhg.2008.13]
|
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</p>
|
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</li>
|
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|
|
<li>
|
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<p class="mim-text-font">
|
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Adebola, A. A., Di Castri, T., He, C.-Z., Salvatierra, L. A., Zhao, J., Brown, K., Lin, C.-S., Worman, H. J., Liem, R. K. H.
|
|
<strong>Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth type 2E phenotype.</strong>
|
|
Hum. Molec. Genet. 24: 2163-2174, 2015.
|
|
|
|
|
|
[PubMed: 25552649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu736]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Agrawal, P. B., Joshi, M., Marinakis, N. S., Schmitz-Abe, K., Ciarlini, P. D. S. C., Sargent, J. C., Markianos, K., De Girolami, U., Chad, D. A., Beggs, A. H.
|
|
<strong>Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.</strong>
|
|
JAMA Neurol. 71: 1413-1420, 2014.
|
|
|
|
|
|
[PubMed: 25264603]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jamaneurol.2014.1432]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berciano, J., Garcia, A., Peeters, K., Gallardo, E., De Vriendt, E., Palayo-Negro, A. L., Infante, J., Jordanova, A.
|
|
<strong>NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.</strong>
|
|
J. Neurol. 262: 1289-1300, 2015.
|
|
|
|
|
|
[PubMed: 25877835]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00415-015-7709-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berciano, J., Peeters, K., Garcia, A., Lopez-Alburquerque, T., Gallardo, E., Hernandez-Fabian, A., Pelayo-Negro, A. L., De Vriendt, E., Infante, J., Jordanova, A.
|
|
<strong>NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.</strong>
|
|
J. Neurol. 263: 361-369, 2016.
|
|
|
|
|
|
[PubMed: 26645395]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00415-015-7985-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brownlees, J., Ackerley, S., Grierson, A. J., Jacobsen, N. J. O., Shea, K., Anderton, B. H., Leigh, P. N., Shaw, C. E., Miller, C. C. J.
|
|
<strong>Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport.</strong>
|
|
Hum. Molec. Genet. 11: 2837-2844, 2002.
|
|
|
|
|
|
[PubMed: 12393795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.23.2837]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Jonghe, P., Mersiyanova, I., Nelis, E., Del Favero, J., Martin, J.-J., Van Broeckhoven, C., Evgrafov, O., Timmerman, V.
|
|
<strong>Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Ann. Neurol. 49: 245-249, 2001.
|
|
|
|
|
|
[PubMed: 11220745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1531-8249(20010201)49:2<245::aid-ana45>3.0.co;2-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elbracht, M., Senderek, J., Schara, U., Nolte, K., Klopstock, T., Roos, A., Reimann, J., Zerres, K., Weis, J., Rudnik-Schoneborn, S.
|
|
<strong>Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Clin. Neuropath. 33: 335-343, 2014.
|
|
|
|
|
|
[PubMed: 24887401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.5414/NP300742]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fabrizi, G. M., Cavallaro, T., Angiari, C., Bertolasi, L., Cabrini, I., Ferrarini, M., Rizzuto, N.
|
|
<strong>Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E.</strong>
|
|
Neurology 62: 1429-1431, 2004.
|
|
|
|
|
|
[PubMed: 15111691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000120664.07186.3c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fabrizi, G. M., Cavallaro, T., Angiari, C., Cabrini, I., Taioli, F., Malerba, G., Bertolasi, L., Rizzuto, N.
|
|
<strong>Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.</strong>
|
|
Brain 130: 394-403, 2007.
|
|
|
|
|
|
[PubMed: 17052987]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awl284]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Georgiou, D.-M., Zidar, J., Korosec, M., Middleton, L. T., Kyriakides, T., Christodoulou, K.
|
|
<strong>A novel NF-L mutation pro22-to-ser is associated with CMT2 in a large Slovenian family.</strong>
|
|
Neurogenetics 4: 93-96, 2002.
|
|
|
|
|
|
[PubMed: 12481988]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-002-0138-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirokawa, N., Takeda, S.
|
|
<strong>Gene targeting studies begin to reveal the function of neurofilament proteins.</strong>
|
|
J. Cell Biol. 143: 1-4, 1998. Note: Erratum: J. Cell Biol. 143: 1142 only, 1998.
|
|
|
|
|
|
[PubMed: 9763415]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.143.1.1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hurst, J., Flavell, D., Julien, J.-P., Meijer, D., Mushynski, W., Grosveld, F.
|
|
<strong>The human neurofilament gene (NEFL) is located on the short arm of chromosome 8.</strong>
|
|
Cytogenet. Cell Genet. 45: 30-32, 1987.
|
|
|
|
|
|
[PubMed: 3036423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J.-J., Butler, I. J., Mancias, P., Papasozomenos, S. C., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., Timmerman, V.
|
|
<strong>Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.</strong>
|
|
Brain 126: 590-597, 2003.
|
|
|
|
|
|
[PubMed: 12566280]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awg059]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Julien, J.-P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., Mushynski, W.
|
|
<strong>The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.</strong>
|
|
Biochim. Biophys. Acta 909: 10-20, 1987.
|
|
|
|
|
|
[PubMed: 3034332]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0167-4781(87)90041-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lees, J. F., Shneidman, P. S., Skuntz, S. F., Carden, M. J., Lazzarini, R. A.
|
|
<strong>The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it.</strong>
|
|
EMBO J. 7: 1947-1955, 1988.
|
|
|
|
|
|
[PubMed: 3138108]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03032.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leung, C. L., Nagan, N., Graham, T. H., Liem, R. K. H.
|
|
<strong>A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie-Tooth disease.</strong>
|
|
Am. J. Med. Genet. 140A: 1021-1025, 2006.
|
|
|
|
|
|
[PubMed: 16619203]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31242]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Levy, E., Liem, R. K. H., D'Eustachio, P., Cowan, N. J.
|
|
<strong>Structure and evolutionary origin of the gene encoding NF-M, the middle-molecular-mass neurofilament protein.</strong>
|
|
Europ. J. Biochem. 166: 71-77, 1987.
|
|
|
|
|
|
[PubMed: 3036526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1432-1033.1987.tb13485.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, H., Zhai, J., Schlaepfer, W. W.
|
|
<strong>RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.</strong>
|
|
Hum. Molec. Genet. 14: 3643-3659, 2005.
|
|
|
|
|
|
[PubMed: 16236762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi392]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mersiyanova, I. V., Perepelov, A. V., Polyakov, A. V., Sitnikov, V. F., Dadali, E. L., Oparin, R. B., Petrin, A. N., Evgrafov, O. V.
|
|
<strong>A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene.</strong>
|
|
Am. J. Hum. Genet. 67: 37-46, 2000.
|
|
|
|
|
|
[PubMed: 10841809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302962]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miltenberger-Miltenyi, G., Janecke, A. R., Wanschitz, J. V., Timmerman, V., Windpassinger, C., Auer-Grumbach, M., Loscher, W. N.
|
|
<strong>Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.</strong>
|
|
Arch. Neurol. 64: 966-970, 2007.
|
|
|
|
|
|
[PubMed: 17620486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.64.7.966]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Nguyen, M. D., Lariviere, R. C., Julien, J.-P.
|
|
<strong>Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.</strong>
|
|
Neuron 30: 135-147, 2001.
|
|
|
|
|
|
[PubMed: 11343650]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0896-6273(01)00268-9]
|
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</p>
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</li>
|
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<li>
|
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<p class="mim-text-font">
|
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Perez-Olle, R., Jones, S. T., Liem, R. K. H.
|
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<strong>Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models.</strong>
|
|
Hum. Molec. Genet. 13: 2207-2220, 2004.
|
|
|
|
|
|
[PubMed: 15282209]
|
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|
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[Full Text: https://doi.org/10.1093/hmg/ddh236]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Previtali, S. C., Zerega, B., Sherman, D. L., Brophy, P. J., Dina, G., King, R. H. M., Salih, M. M., Feltri, L., Quattrini, A., Ravazzolo, R., Wrabetz, L., Monaco, A. P., Bolino, A.
|
|
<strong>Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve.</strong>
|
|
Hum. Molec. Genet. 12: 1713-1723, 2003.
|
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|
|
|
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[PubMed: 12837694]
|
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|
|
|
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[Full Text: https://doi.org/10.1093/hmg/ddg179]
|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Rebelo, A. P., Abrams, A. J., Cottenie, E., Horga, A., Gonzalez, M., Bis, D. M., Sanchez-Mejias, A., Pinto, M., Buglo, E., Markel, K., Prince, J., Laura, M., and 10 others.
|
|
<strong>Cryptic amyloidogenic elements in the 3-prime UTRs of neurofilament genes trigger axonal neuropathy.</strong>
|
|
Am. J. Hum. Genet. 98: 597-614, 2016.
|
|
|
|
|
|
[PubMed: 27040688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2016.02.022]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sasaki, T., Gotow, T., Shiozaki, M., Sakaue, F., Saito, T., Julien, J.-P., Uchiyama, Y., Hisanaga, S.
|
|
<strong>Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie-Tooth disease mutants.</strong>
|
|
Hum. Molec. Genet. 15: 943-952, 2006.
|
|
|
|
|
|
[PubMed: 16452125]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Somerville, M. J., McLachlan, D. R., Percy, M. E.
|
|
<strong>Localization of the 68000-Da human neurofilament gene (NF68) using a murine cDNA probe.</strong>
|
|
Genome 30: 499-500, 1988.
|
|
|
|
|
|
[PubMed: 3145240]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1139/g88-083]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamamoto, M., Yoshihara, T., Hattori, N., Sobue, G.
|
|
<strong>Glu528del in NEFL is a polymorphic variant rather than a disease-causing mutation for Charcot-Marie-Tooth disease in Japan.</strong>
|
|
Neurogenetics 5: 75-77, 2004.
|
|
|
|
|
|
[PubMed: 14586770]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-003-0159-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yum, S. W., Zhang, J., Mo, K., Li, J., Scherer, S. S.
|
|
<strong>A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy.</strong>
|
|
Ann. Neurol. 66: 759-770, 2009.
|
|
|
|
|
|
[PubMed: 20039262]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21728]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Zhai, J., Lin, H., Julien, J.-P., Schlaepfer, W. W.
|
|
<strong>Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.</strong>
|
|
Hum. Molec. Genet. 16: 3103-3116, 2007.
|
|
|
|
|
|
[PubMed: 17881652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm272]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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Zhu, Q., Couillard-Despres, S., Julien, J.-P.
|
|
<strong>Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.</strong>
|
|
Exp. Neurol. 148: 299-316, 1997.
|
|
|
|
|
|
[PubMed: 9398473]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/exnr.1997.6654]
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</p>
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</li>
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|
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<li>
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<strong>The novel neurofilament light (NEFL) mutation glu397lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.</strong>
|
|
Neuromusc. Disord. 14: 147-157, 2004.
|
|
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|
|
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[PubMed: 14733962]
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[Full Text: https://doi.org/10.1016/j.nmd.2003.10.003]
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Alan F. Scott - updated : 01/07/2022<br>Cassandra L. Kniffin - updated : 02/21/2018<br>Cassandra L. Kniffin - updated : 4/27/2016<br>Cassandra L. Kniffin - updated : 6/10/2015<br>Cassandra L. Kniffin - updated : 8/30/2010<br>Cassandra L. Kniffin - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 6/22/2009<br>George E. Tiller - updated : 4/23/2009<br>Cassandra L. Kniffin - updated : 4/1/2008<br>George E. Tiller - updated : 4/5/2007<br>Marla J. F. O'Neill - updated : 5/25/2006<br>George E. Tiller - updated : 5/4/2005<br>Cassandra L. Kniffin - updated : 1/25/2005<br>George E. Tiller - updated : 4/1/2004<br>Cassandra L. Kniffin - updated : 3/17/2004<br>Cassandra L. Kniffin - updated : 5/1/2003<br>Cassandra L. Kniffin - updated : 4/30/2003<br>Victor A. McKusick - updated : 1/8/2003<br>Dawn Watkins-Chow - updated : 11/5/2002<br>Victor A. McKusick - updated : 9/6/2000
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