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<title>
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Entry
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- *123590 - CRYSTALLIN, ALPHA-B; CRYAB
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- OMIM
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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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<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 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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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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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">*123590</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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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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</li>
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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>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/123590">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
|
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</a>
|
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</h4>
|
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</div>
|
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
|
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
|
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</span>
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000109846;t=ENST00000650687" 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=1410" 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=123590" 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=ENSG00000109846;t=ENST00000650687" 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_001289807,NM_001289808,NM_001330379,NM_001368245,NM_001368246,NM_001885" 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_001289808" 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=123590" 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=00428&isoform_id=00428_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/CRYAB" 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/117385,181076,256399,537532,2852648,4503057,13937813,30582379,40046778,40046782,119587566,119587567,119587568,119587569,119587570,119587571,167887506,189054219,194380530,209402766,227018373,577019571,577019573,1002005034,1002005036,1002005038,1002005040,1002005042,1060099179,1564385576,1564386053,2462522985" 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/P02511" 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=1410" 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=ENSG00000109846;t=ENST00000650687" 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=CRYAB" 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=CRYAB" 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+1410" 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/CRYAB" 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:1410" 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/1410" 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=chr11&hgg_gene=ENST00000650687.2&hgg_start=111908564&hgg_end=111923740&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=123590[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=123590[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/ENSG00000109846" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=CRYAB" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=CRYAB" 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=CRYAB" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/CRYAB" 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=CRYAB&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/PA26907" 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">
|
|
<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:2389" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0011296.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88516" 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/CRYAB#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:88516" 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/1410/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1410" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00002011;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00002011 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00002012;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00002012 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00002013;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00002013 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00011906;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00011906 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040718-419" 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:1410" 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=CRYAB&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> 399336001, 782883004<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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123590
|
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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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CRYSTALLIN, ALPHA-B; CRYAB
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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">
|
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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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CRYSTALLIN, ALPHA-2; CRYA2<br />
|
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HEAT-SHOCK PROTEIN BETA-5; HSPB5
|
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</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>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CRYAB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CRYAB</a></em></strong>
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/11/925?start=-3&limit=10&highlight=925">11q23.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:111908564-111923740&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'})">11:111,908,564-111,923,740</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</p>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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Location
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
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<a href="/clinicalSynopsis/table?mimNumber=615184,613763,608810,613869" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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<th>
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Inheritance
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<th>
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Phenotype <br /> mapping key
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</th>
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</thead>
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<tbody>
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<tr>
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<td rowspan="4">
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<span class="mim-font">
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<a href="/geneMap/11/925?start=-3&limit=10&highlight=925">
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11q23.1
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</a>
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</td>
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<span class="mim-font">
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Cardiomyopathy, dilated, 1II
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<td>
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<span class="mim-font">
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<a href="/entry/615184"> 615184 </a>
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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 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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Cataract 16, multiple types
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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/613763"> 613763 </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>
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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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<tr>
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<span class="mim-font">
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Myopathy, myofibrillar, 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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<a href="/entry/608810"> 608810 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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<tr>
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<span class="mim-font">
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Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
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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/613869"> 613869 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<div class="btn-group">
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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/123590" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/123590" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</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="text" class="mim-anchor"></a>
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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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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<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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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The crystallins compose approximately 90% of the soluble protein of the vertebrate eye lens and include 3 major families of ubiquitously expressed crystallins: alpha (e.g., CRYAA; <a href="/entry/123580">123580</a>), beta (e.g., CRYBA1; <a href="/entry/123610">123610</a>), and gamma (e.g., CRYGA; <a href="/entry/123660">123660</a>). Alpha-B-crystallin is a member of the small heat-shock protein family (<a href="#5" class="mim-tip-reference" title="Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J. <strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong> Genomics 7: 594-601, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387586</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90204-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387586">Dubin et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="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 class="mim-text-font">
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<p><a href="#5" class="mim-tip-reference" title="Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J. <strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong> Genomics 7: 594-601, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387586</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90204-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387586">Dubin et al. (1990)</a> presented the complete nucleotide sequence of the human CRYAB gene, which encodes a 175-amino acid protein with a molecular mass of 20 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 the mouse, <a href="#6" class="mim-tip-reference" title="Dubin, R. A., Wawrousek, E. F., Piatigorsky, J. <strong>Expression of the murine alpha-B-crystallin gene is not restricted to the lens.</strong> Molec. Cell Biol. 9: 1083-1091, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2725488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2725488</a>] [<a href="https://doi.org/10.1128/mcb.9.3.1083-1091.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2725488">Dubin et al. (1989)</a> found that the Cryab gene is expressed in the lens, heart, skeletal muscle, kidney, and lung. In the rat, <a href="#14" class="mim-tip-reference" title="Iwaki, T., Kume-Iwaki, A., Goldman, J. E. <strong>Cellular distribution of alpha-B-crystallin in non-lenticular tissues.</strong> J. Histochem. Cytochem. 38: 31-39, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2294148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2294148</a>] [<a href="https://doi.org/10.1177/38.1.2294148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2294148">Iwaki et al. (1990)</a> found Cryab expression in lens, iris, heart, skeletal muscle, certain regions of the kidney, Schwann cells of peripheral nerves, glia in the central nervous system, and decidual cells of the placenta. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2294148+2725488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By functional analysis of a CRYAB promoter fragment fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, <a href="#5" class="mim-tip-reference" title="Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J. <strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong> Genomics 7: 594-601, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387586</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90204-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387586">Dubin et al. (1990)</a> found that the fragment contains regulatory elements that function predominantly, but not exclusively, in lens. Although alpha-B-crystallin had been reported to accumulate in brain cells in Alexander disease (<a href="/entry/203450">203450</a>) (<a href="#15" class="mim-tip-reference" title="Iwaki, T., Kume-Iwaki, A., Leim, R. K. H., Goldman, J. E. <strong>Alpha-B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain.</strong> Cell 57: 71-78, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2539261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2539261</a>] [<a href="https://doi.org/10.1016/0092-8674(89)90173-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2539261">Iwaki et al., 1989</a>), <a href="#5" class="mim-tip-reference" title="Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J. <strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong> Genomics 7: 594-601, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387586</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90204-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387586">Dubin et al. (1990)</a> found that the promoter fragment was insufficient to promote transcription in a glial cell line that synthesizes high levels of the endogenous CRYAB gene product. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2387586+2539261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<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><a href="#5" class="mim-tip-reference" title="Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J. <strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong> Genomics 7: 594-601, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387586</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90204-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387586">Dubin et al. (1990)</a> determined that the CRYAB gene contains 3 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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<a id="mapping" class="mim-anchor"></a>
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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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<p>By use of a CRYA2 genomic probe in connection with mouse-human somatic cell hybrid DNA, <a href="#23" class="mim-tip-reference" title="Ngo, J. T., Klisak, I., Dubin, R. A., Piatigorsky, J., Mohandas, T., Sparkes, R. S., Bateman, J. B. <strong>Assignment of the alpha B crystallin gene to human chromosome 11.</strong> Genomics 5: 665-669, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2591958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2591958</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90106-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2591958">Ngo et al. (1989)</a> assigned the gene to chromosome 11; by in situ hybridization, they regionalized the locus to 11q22.3-q23.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2591958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By study of a panel of human/rodent hybrid cell lines using a probe consisting of the third exon of the hamster alpha-B-crystallin gene, <a href="#2" class="mim-tip-reference" title="Brakenhoff, R. H., Geurts van Kessel, A. H. M., Oldenburg, M., Wijnen, J. T., Bloemendal, H., Meera Khan, P., Schoenmakers, J. G. G. <strong>Human alpha-B-crystallin (CRYA2) gene mapped to chromosome 11q12-q23.</strong> Hum. Genet. 85: 237-240, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370055</a>] [<a href="https://doi.org/10.1007/BF00193203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2370055">Brakenhoff et al. (1990)</a> assigned the CRYA2 gene to chromosome 11. Using cell hybrids containing translocated and/or partially deleted human chromosome 11, they localized the CRYA2 gene further to 11q12-q23. <a href="#16" class="mim-tip-reference" title="Jeanpierre, C., Austruy, E., Delattre, O., Jones, C., Junien, C. <strong>Subregional physical mapping of an alpha-B-crystallin sequence and of a new expressed sequence D11S877E to human 11q.</strong> Mammalian Genome 4: 104-108, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8431633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8431633</a>] [<a href="https://doi.org/10.1007/BF00290434" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8431633">Jeanpierre et al. (1993)</a> showed that the CRYA2 gene lies proximal to the 11q23.2 breakpoint defined by the constitutional t(11;22) and distal to the 11q22.1 breakpoint of a constitutional interstitial deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8431633+2370055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#18" class="mim-tip-reference" title="Laganowsky, A., Liu, C., Sawaya, M. R., Whitelegge, J. P., Park, J., Zhao, M., Pensalfini, A., Soriaga, A. B., Landau, M., Teng, P. K., Cascio, D., Glabe, C., Eisenberg, D. <strong>Atomic view of a toxic amyloid small oligomer.</strong> Science 335: 1228-1231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22403391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22403391</a>] [<a href="https://doi.org/10.1126/science.1213151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22403391">Laganowsky et al. (2012)</a> identified a segment of the amyloid-forming protein alpha-B crystallin that forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer revealed a cylindrical barrel, formed from 6 antiparallel protein strands, which <a href="#18" class="mim-tip-reference" title="Laganowsky, A., Liu, C., Sawaya, M. R., Whitelegge, J. P., Park, J., Zhao, M., Pensalfini, A., Soriaga, A. B., Landau, M., Teng, P. K., Cascio, D., Glabe, C., Eisenberg, D. <strong>Atomic view of a toxic amyloid small oligomer.</strong> Science 335: 1228-1231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22403391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22403391</a>] [<a href="https://doi.org/10.1126/science.1213151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22403391">Laganowsky et al. (2012)</a> termed a cylindrin. The cylindrin structure is compatible with a sequence segment from the beta-amyloid protein of Alzheimer disease. <a href="#18" class="mim-tip-reference" title="Laganowsky, A., Liu, C., Sawaya, M. R., Whitelegge, J. P., Park, J., Zhao, M., Pensalfini, A., Soriaga, A. B., Landau, M., Teng, P. K., Cascio, D., Glabe, C., Eisenberg, D. <strong>Atomic view of a toxic amyloid small oligomer.</strong> Science 335: 1228-1231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22403391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22403391</a>] [<a href="https://doi.org/10.1126/science.1213151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22403391">Laganowsky et al. (2012)</a> concluded that cylindrins offer models for the hitherto elusive structures of amyloid oligomers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22403391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#34" class="mim-tip-reference" title="van Noort, J. M., van Sechel, A. C., Bajramovic, J. J., El Quagmiri, M., Polman, C. H., Lassmann, H., Ravid, R. <strong>The small heat-shock protein alpha-B-crystallin as candidate autoantigen in multiple sclerosis.</strong> Nature 375: 798-801, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7596414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7596414</a>] [<a href="https://doi.org/10.1038/375798a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7596414">Van Noort et al. (1995)</a> examined proliferative responses of human peripheral blood T cells to the complete collection of myelin proteins, including alpha-B-crystallin. They found that alpha-B-crystallin was a highly immunogenic protein to which T cells from multiple sclerosis (MS; <a href="/entry/126200">126200</a>) patients and from healthy controls showed dominant responses. Immunohistochemical examination of MS lesions revealed the presence of oligodendrocytes and astrocytes with raised CRYA2 expression, which was not found in unaffected myelin, suggesting that the CRYA2 protein may be an autoantigen in MS. The authors noted that alpha-B-crystallin had been detected in brains of patients with other neurologic diseases, including Alzheimer (<a href="/entry/104300">104300</a>), Parkinson (<a href="/entry/168600">168600</a>, <a href="/entry/168601">168601</a>), Pick (<a href="/entry/172700">172700</a>), and Huntington (<a href="/entry/143100">143100</a>) diseases. <a href="#33" class="mim-tip-reference" title="Steinman, L. <strong>Presenting an odd autoantigen.</strong> Nature 375: 739-740, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7541112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7541112</a>] [<a href="https://doi.org/10.1038/375739b0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7541112">Steinman (1995)</a> discussed the significance of the immune reaction against alpha-B-crystallin in the pathology of MS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7541112+7596414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The alpha-crystallin subunits alpha-A and alpha-B each can form an oligomer by itself or with the other. <a href="#8" class="mim-tip-reference" title="Fu, L., Liang, J. J.-N. <strong>Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay.</strong> J. Biol. Chem. 277: 4255-4260, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11700327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11700327</a>]" pmid="11700327">Fu and Liang (2002)</a> used a 2-hybrid system to study heterogeneous interactions among lens crystallins of different classes. They found interactions between alpha-A- (or alpha-B-) and beta-B2- or gamma-C- (<a href="/entry/123680">123680</a>)-crystallins, but the intensity of interaction was one-third that of alpha-A-alpha-B interactions. HSP27 (<a href="/entry/602195">602195</a>), a member of the small heat-shock protein family, showed similar interaction properties with alpha-B-crystallin. Experiments with N- and C-terminal domain-truncated mutants demonstrated that both N- and C-terminal domains were important in alpha-A-crystallin self-interaction, but that only the C-terminal domain was important in alpha-B-crystallin self-interaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11700327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cataractogenesis (development of lens opacity) is believed to be a consequence of accumulation of insoluble aggregates and gross-linked products of alpha-, beta-, and gamma-crystallins. The insolubilization of crystallins is thought to be initiated by posttranslational modifications that change their structural and functional properties. <a href="#32" class="mim-tip-reference" title="Srivastava, O. P., Srivastava, K. <strong>Existence of deamidated alpha-B-crystallin fragments in normal and cataractous human lenses.</strong> Molec. Vis. 9: 110-118, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707643</a>]" pmid="12707643">Srivastava and Srivastava (2003)</a> showed that the asparagine-146 residue (N146) of human alpha-B-crystallin undergoes in vivo deamidation, and several fragments containing this modification were found in both water-soluble and -insoluble protein fractions of normal and cataractous human lenses. <a href="#10" class="mim-tip-reference" title="Gupta, R., Srivastava, O. P. <strong>Effect of deamidation of asparagine 146 on functional and structural properties of human lens alpha-B-crystallin.</strong> Invest. Ophthal. Vis. Sci. 45: 206-214, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14691175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14691175</a>] [<a href="https://doi.org/10.1167/iovs.03-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14691175">Gupta and Srivastava (2004)</a> showed that deamidation of N146 but not of N78 of CRYAB had profound effects on the structural and functional properties of alpha-B-crystallin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12707643+14691175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunohistochemical analysis, <a href="#22" class="mim-tip-reference" title="Moyano, J. V., Evans, J. R., Chen, F., Lu, M., Werner, M. E., Yehiely, F., Diaz, L. K., Turbin, D., Karaca, G., Wiley, E., Nielsen, T. O., Perou, C. M., Cryns, V. L. <strong>Alpha-B-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.</strong> J. Clin. Invest. 116: 261-270, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16395408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16395408</a>] [<a href="https://doi.org/10.1172/JCI25888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16395408">Moyano et al. (2006)</a> found that CRYAB was expressed in 18 (45%) of 40 basal-like breast tumors and predicted poor survival of breast cancer patients independently of other prognostic markers. Overexpression of CRYAB transformed immortalized human mammary epithelial cells (MECs) and conferred neoplastic-like changes, which were suppressed by MEK (see MAP2K1; <a href="/entry/176872">176872</a>) inhibitors. Immortalized human MECs overexpressing CRYAB formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16395408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Wang, J., Xu, G., Li, H., Gonzales, V., Fromholt, D., Karch, C., Copeland, N. G., Jenkins N. A., Borchelt, D. R. <strong>Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates degeneration: alpha-B-crystallin modulates aggregation.</strong> Hum. Molec. Genet. 14: 2335-2347, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000321</a>] [<a href="https://doi.org/10.1093/hmg/ddi236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16000321">Wang et al. (2005)</a> found that in SOD1 (<a href="/entry/147450">147450</a>)-mutant mouse cells alpha-B-crystallin suppressed aggregation of mutant SOD1 in somatodendritic compartments. In vivo, alpha-B-crystallin immunoreactivity was most abundant in oligodendrocytes and upregulated in astrocytes of symptomatic mice; neither of these cell types accumulated mutant SOD1 immunoreactivity. <a href="#38" class="mim-tip-reference" title="Wang, J., Xu, G., Li, H., Gonzales, V., Fromholt, D., Karch, C., Copeland, N. G., Jenkins N. A., Borchelt, D. R. <strong>Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates degeneration: alpha-B-crystallin modulates aggregation.</strong> Hum. Molec. Genet. 14: 2335-2347, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000321</a>] [<a href="https://doi.org/10.1093/hmg/ddi236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16000321">Wang et al. (2005)</a> suggested that damage to motor neuron cell bodies and dendrites within the spinal cord may be sufficient to induce motor neuron disease, and that activities of chaperones may modulate the cellular specificity of mutant SOD1 accumulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16000321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Shao, W., Zhang, S., Tang, M., Zhang, X., Zhou, Z., Yin, Y., Zhou, Q., Huang, Y., Liu, Y., Wawrousek, E., Chen, T., Li, S., Xu, M., Zhou, J., Hu, G., Zhou, J. <strong>Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha-B-crystallin.</strong> Nature 494: 90-94, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23242137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23242137</a>] [<a href="https://doi.org/10.1038/nature11748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23242137">Shao et al. (2013)</a> showed that the astrocytic dopamine D2 receptor (DRD2; <a href="/entry/126450">126450</a>) modulates innate immunity through CRYAB, which is known to suppress inflammation. <a href="#31" class="mim-tip-reference" title="Shao, W., Zhang, S., Tang, M., Zhang, X., Zhou, Z., Yin, Y., Zhou, Q., Huang, Y., Liu, Y., Wawrousek, E., Chen, T., Li, S., Xu, M., Zhou, J., Hu, G., Zhou, J. <strong>Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha-B-crystallin.</strong> Nature 494: 90-94, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23242137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23242137</a>] [<a href="https://doi.org/10.1038/nature11748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23242137">Shao et al. (2013)</a> demonstrated that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Drd2-null astrocytes became hyperresponsive to immune stimuli, with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wildtype mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. <a href="#31" class="mim-tip-reference" title="Shao, W., Zhang, S., Tang, M., Zhang, X., Zhou, Z., Yin, Y., Zhou, Q., Huang, Y., Liu, Y., Wawrousek, E., Chen, T., Li, S., Xu, M., Zhou, J., Hu, G., Zhou, J. <strong>Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha-B-crystallin.</strong> Nature 494: 90-94, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23242137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23242137</a>] [<a href="https://doi.org/10.1038/nature11748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23242137">Shao et al. (2013)</a> concluded that their study indicated that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provided a strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during aging and disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23242137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Yamashita, A., Taniwaki, T., Kaikoi, Y., Yamazaki, T. <strong>Protective role of the endoplasmic reticulum protein mitsugumin23 against ultraviolet C-induced cell death.</strong> FEBS Lett. 587: 1299-1303, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23542032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23542032</a>] [<a href="https://doi.org/10.1016/j.febslet.2013.03.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23542032">Yamashita et al. (2013)</a> found that knockdown of the endoplasmic reticulum (ER) protein TMEM109 (<a href="/entry/619168">619168</a>) in HEK293T cells caused a 15% increase in apoptosis in response to ultraviolet C (UVC) irradiation compared with controls. Conversely, overexpression of mouse Tmem109 improved cell survival following UVC irradiation. The UVC sensitivity phenotype required the second cytoplasmic region (CP2) of TMEM109. Yeast 2-hybrid and coimmunoprecipitation assays showed that the CP2 region of mouse Tmem109 interacted with the C-terminal half of human CRYAB. The extent of UVC-induced cell death in TMEM109-knockdown, CRYAB-knockdown, and TMEM109/CRYAB dual-knockdown cells was equivalent, suggesting that TMEM109 and CRYAB function together rather than in parallel. A fusion protein of full-length human CRYAB and the first transmembrane domain of mouse Tmem109, which was predicted to anchor to the ER, also increased UVC resistance, suggesting that TMEM109 protects against UVC by accumulating CRYAB near the ER. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23542032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Myofibrillar Myopathy 2</em></strong></p><p>
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In affected members of a family with an autosomal dominant myofibrillar myopathy (MFM2; <a href="/entry/608810">608810</a>) reported by <a href="#7" class="mim-tip-reference" title="Fardeau, M., Godet-Guillain, J., Tome, F. M., Collin, H., Gardeau, S., Boffety, C., Vernant, P. <strong>Une nouvelle affection musculaire familiale, definie par l'accumulation intra-sarco-plasmique d'un materiel granulo-filamenta ire dense en microscopie electronique.</strong> Rev. Neurol. 134: 411-425, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/570292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">570292</a>]" pmid="570292">Fardeau et al. (1978)</a>, <a href="#36" class="mim-tip-reference" title="Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M.-C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.-M., Paulin, D., Fardeau, M. <strong>A missense mutation in the alpha-B-crystallin chaperone gene causes a desmin-related myopathy.</strong> Nature Genet. 20: 92-95, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731540</a>] [<a href="https://doi.org/10.1038/1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731540">Vicart et al. (1998)</a> identified a heterozygous mutation in the CRYAB gene (<a href="#0001">123590.0001</a>). Affected individuals also exhibited clinical or electrocardiographic signs of hypertrophic cardiomyopathy and discrete lens opacities. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=570292+9731540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients with myofibrillar myopathy, <a href="#30" class="mim-tip-reference" title="Selcen, D., Engel, A. G. <strong>Myofibrillar myopathy caused by novel dominant negative alpha-B-crystallin mutations.</strong> Ann. Neurol. 54: 804-810, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681890</a>] [<a href="https://doi.org/10.1002/ana.10767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14681890">Selcen and Engel (2003)</a> identified 2 different heterozygous mutations in the CRYAB gene (<a href="#0003">123590.0003</a>; <a href="#0004">123590.0004</a>). Expression studies of both mutations were consistent with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro experiments using different CRYAB mutants, <a href="#12" class="mim-tip-reference" title="Hayes, V. H., Devlin, G., Quinlan, R. A. <strong>Truncation of alpha-beta-crystallin by the myopathy-causing Q151X mutation significantly destabilizes the protein leading to aggregate formation in transfected cells.</strong> J. Biol. Chem. 283: 10500-10512, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18230612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18230612</a>] [<a href="https://doi.org/10.1074/jbc.M706453200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18230612">Hayes et al. (2008)</a> found that the C-terminal extension was important for oligomerization. The Q151X mutation (<a href="#0004">123590.0004</a>) decreased oligomerization and even increased some chaperone activities, but it also significantly destabilized the protein and caused self-aggregation. The 450delA (<a href="#0002">123590.0002</a>) and 464delCT (<a href="#0003">123590.0003</a>) mutants could only be refolded and assayed as a complex with wildtype CRYAB. <a href="#12" class="mim-tip-reference" title="Hayes, V. H., Devlin, G., Quinlan, R. A. <strong>Truncation of alpha-beta-crystallin by the myopathy-causing Q151X mutation significantly destabilizes the protein leading to aggregate formation in transfected cells.</strong> J. Biol. Chem. 283: 10500-10512, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18230612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18230612</a>] [<a href="https://doi.org/10.1074/jbc.M706453200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18230612">Hayes et al. (2008)</a> concluded that mutations in the C-terminal extension destabilize the protein and increase its tendency to self-aggregate. It is this tendency, rather than a loss of chaperone activity, that is the major pathogenic factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18230612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 all affected members of a family of North African origin with myofibrillar myopathy, posterior polar cataract, and dilated cardiomyopathy, <a href="#28" class="mim-tip-reference" title="Sacconi, S., Feasson, L., Antoine, J. C., Pecheux, C., Bernard, R., Cobo, A. M., Casarin, A., Salviati, L., Desnuelle, C., Urtizberea, A. <strong>A novel CRYAB mutation resulting in multisystemic disease.</strong> Neuromusc. Disord. 22: 66-72, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21920752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21920752</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.07.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21920752">Sacconi et al. (2012)</a> identified heterozygosity for a missense mutation in the CRYAB gene (D109H; <a href="#0011">123590.0011</a>). The mutation was not found in unaffected family members or 50 ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21920752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Fatal Infantile Hypertonic Myofibrillar Myopathy</em></strong></p><p>
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In 8 patients with fatal infantile hypertonic myofibrillar myopathy (<a href="/entry/613869">613869</a>), <a href="#4" class="mim-tip-reference" title="Del Bigio, M. R., Chudley, A. E., Sarnat, H. B., Campbell, C., Goobie, S., Chodirker, B. N., Selcen, D. <strong>Infantile muscular dystrophy in Canadian aboriginals is an alpha-B-crystallinopathy.</strong> Ann. Neurol. 69: 866-871, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21337604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21337604</a>] [<a href="https://doi.org/10.1002/ana.22331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21337604">Del Bigio et al. (2011)</a> identified the same homozygous 1-bp deletion in the CRYAB gene (60delC; <a href="#0005">123590.0005</a>). All patients were Canadian aboriginals of Cree descent, consistent with a founder effect. The phenotype was characterized by onset in the first weeks of life of rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21337604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cataract 16, Multiple Types</em></strong></p><p>
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In a 4-generation family of English descent with autosomal dominant congenital posterior polar cataracts (CTRCT16; <a href="/entry/613763">613763</a>), <a href="#1" class="mim-tip-reference" title="Berry, V., Francis, P., Reddy, M. A., Collyer, D., Vithana, E., MacKay, I., Dawson, G., Carey, A. H., Moore, A., Bhattacharya, S. S., Quinlan, R. A. <strong>Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.</strong> Am. J. Hum. Genet. 69: 1141-1145, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11577372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11577372</a>] [<a href="https://doi.org/10.1086/324158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11577372">Berry et al. (2001)</a> identified a deletion mutation in the CRYAB gene (<a href="#0002">123590.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11577372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fu, L., Liang, J. J.-N. <strong>Alteration of protein-protein interactions of congenital cataract crystallin mutants.</strong> Invest. Ophthal. Vis. Sci. 44: 1155-1159, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601044</a>]" pmid="12601044">Fu and Liang (2003)</a> studied the effect of crystallin gene mutations that result in congenital cataract on protein-protein interactions. Interactions between mutated crystallins alpha-A (R116C; <a href="/entry/123580#0001">123580.0001</a>), alpha-B (R120G; <a href="#0001">123590.0001</a>), and gamma-C (T5P; <a href="/entry/123680#0001">123680.0001</a>) and the corresponding wildtype proteins, as well as with wildtype beta-B2-crystallin (<a href="/entry/123620">123620</a>) and HSP27, were analyzed in a mammalian cell 2-hybrid system. For mutated alpha-A-crystallin, interactions with wildtype beta-B2-crystallin and gamma-C-crystallin decreased and those with wildtype alpha-B-crystallin and HSP27 increased. For mutated alpha-B-crystallin, interactions with wildtype alpha-A-crystallin and alpha-B-crystallin decreased, but those with wildtype beta-B2-crystallin and gamma-C-crystallin increased slightly. For mutated gamma-C-crystallin, most of the interactions were decreased. The results indicated that crystallin mutations involved in congenital cataracts altered protein-protein interactions, which might contribute to decreased protein solubility and formation of cataract. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 large 5-generation Chinese family with congenital lamellar cataract who were negative for mutation at known hotspots in 9 cataract-associated genes, <a href="#20" class="mim-tip-reference" title="Liu, Y., Zhang, X., Luo, L., Wu, M., Zeng, R., Cheng, G., Hu, B., Liu, B., Liang, J. J., Shang, F. <strong>A novel alpha-B-crystallin mutation associated with autosomal dominant congenital lamellar cataract.</strong> Invest. Ophthal. Vis. Sci. 47: 1069-1075, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505043</a>] [<a href="https://doi.org/10.1167/iovs.05-1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16505043">Liu et al. (2006)</a> identified heterozygosity for a missense mutation in CRYAB (D140N; <a href="#0008">123590.0008</a>) that segregated with disease and was not found in 100 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 4-generation Chinese family with congenital posterior polar cataract mapping to 11q22, <a href="#19" class="mim-tip-reference" title="Liu, M., Ke, T., Wang, Z., Yang, Q., Chang, W., Jiang, F., Tang, Z., Li, H., Ren, X., Wang, X., Wang, T., Li, Q., Yang, J., Liu, J., Wang, Q. K. <strong>Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family.</strong> Invest. Ophthal. Vis. Sci. 47: 3461-3466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16877416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16877416</a>] [<a href="https://doi.org/10.1167/iovs.05-1438" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16877416">Liu et al. (2006)</a> identified a heterozygous missense mutation in the CRYAB gene (P20S; <a href="#0009">123590.0009</a>) that segregated fully with disease in the family and was not found in 200 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16877416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 an affected mother and 4 affected children from a consanguineous Saudi family with cataract mapping to 11q21-q23, <a href="#29" class="mim-tip-reference" title="Safieh, L. A., Khan, A. O., Alkuraya, F. S. <strong>Identification of a novel CRYAB mutation associated with autosomal recessive juvenile cataract in a Saudi family.</strong> Molec. Vis. 15: 980-984, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19461931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19461931</a>]" pmid="19461931">Safieh et al. (2009)</a> identified homozygosity for a missense mutation in the CRYAB gene (R56W; <a href="#0010">123590.0010</a>). The unaffected father was heterozygous for the mutation, which was not found in 150 Saudi controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19461931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cardiomyopathy, Dilated, 1II</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Inagaki, N., Hayashi, T., Arimura, T., Koga, Y., Takahashi, M., Shibata, H., Teraoka, K., Chikamori, T., Yamashina, A., Kimura, A. <strong>Alpha-B-crystallin mutation in dilated cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 342: 379-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16483541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16483541</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.01.154" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16483541">Inagaki et al. (2006)</a> analyzed the CRYAB gene in 130 unrelated Japanese patients with dilated cardiomyopathy (CMD1II; <a href="/entry/615184">615184</a>) who were negative for mutations in known CMD genes, and identified a heterozygous missense mutation (R157H; <a href="#0006">123590.0006</a>) in a 71-year-old woman with mild, late-onset disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16483541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Pilotto, A., Marziliano, N., Pasotti, M., Grasso, M., Costante, A. M., Arbustini, E. <strong>Alpha-B-crystallin mutation in dilated cardiomyopathies: low prevalence in a consecutive series of 200 unrelated probands.</strong> Biochem. Biophys. Res. Commun. 346: 1115-1117, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16793013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16793013</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.05.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16793013">Pilotto et al. (2006)</a> screened the CRYAB gene in 200 consecutive patients diagnosed with autosomal dominant or sporadic CMD, and identified a heterozygous missense mutation (G154S; <a href="#0007">123590.0007</a>) in a 48-year-old woman with recently diagnosed CMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16793013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Associations Pending Confirmation</em></strong></p><p>
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<a href="#35" class="mim-tip-reference" title="van Veen, T., van Winsen, L., Crusius, J. B. A., Kalkers, N. F., Barkhof, F., Pena, A. S., Polman, C. H., Uitdehaag, B. M. J. <strong>Alpha-B-crystallin genotype has impact on the multiple sclerosis phenotype.</strong> Neurology 61: 1245-1249, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14610128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14610128</a>] [<a href="https://doi.org/10.1212/01.wnl.0000091861.27246.9e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14610128">Van Veen et al. (2003)</a> presented evidence suggesting that polymorphisms in the promoter region of the CRYAB gene may influence the clinical phenotype of multiple sclerosis (<a href="/entry/126200">126200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14610128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Alpha-B-crystallin is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has antiapoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T cell immunity to the myelin sheath from multiple sclerosis brain. <a href="#24" class="mim-tip-reference" title="Ousman, S. S., Tomooka, B. H., van Noort, J. M., Wawrousek, E. F., O'Connor, K. C., Hafler, D. A., Sobel, R. A., Robinson, W. H., Steinman, L. <strong>Protective and therapeutic role for alpha-beta-crystallin in autoimmune demyelination.</strong> Nature 448: 474-479, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17568699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17568699</a>] [<a href="https://doi.org/10.1038/nature05935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17568699">Ousman et al. (2007)</a> demonstrated that CRYAB is a potent negative regulator acting as a brake on several inflammatory pathways in both the immune system and central nervous system. Cryab-null mice showed worse experimental autoimmune encephalomyelitis at the acute and progressive phases, with higher Th1 and Th17 cytokine secretion from T cells and macrophages, and more intense central nervous system (CNS) inflammation, compared with their wildtype counterparts. Furthermore, Cryab-null astrocytes showed more cleaved caspase-3 (<a href="/entry/600636">600636</a>) and more TUNEL staining, indicating an antiapoptotic function of Cryab. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17568699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Alexander disease is a primary disorder of astrocytes caused by dominant mutations in the gene for glial fibrillary acidic protein (GFAP; <a href="/entry/137780">137780</a>). These mutations lead to protein aggregation and formation of Rosenthal fibers, complex astrocytic inclusions that contain GFAP, vimentin (VIM; <a href="/entry/193060">193060</a>), plectin (PLEC1; <a href="/entry/601282">601282</a>), ubiquitin (UBB; <a href="/entry/191339">191339</a>), Hsp27, and CRYAB. CRYAB regulates GFAP assembly, and elevation of CRYAB is a consistent feature of Alexander disease; however, its role in Rosenthal fibers and disease pathology is not known. In a mouse model of Alexander disease, <a href="#11" class="mim-tip-reference" title="Hagemann, T. L., Boelens, W. C., Wawrousek, E. F., Messing, A. <strong>Suppression of GFAP toxicity by alpha-B-crystallin in mouse models of Alexander disease.</strong> Hum. Molec. Genet. 18: 1190-1199, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19129171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19129171</a>] [<a href="https://doi.org/10.1093/hmg/ddp013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19129171">Hagemann et al. (2009)</a> showed that loss of Cryab resulted in increased mortality, whereas elevation of Cryab rescued animals from terminal seizures. When mice with Rosenthal fibers induced by overexpression of GFAP were crossed into a Cryab-null background, over half died at 1 month of age. Restoration of Cryab expression through the GFAP promoter reversed this outcome, showing the effect was astrocyte-specific. Conversely, in mice carrying an Alexander disease-associated mutation and in mice overexpressing wildtype GFAP, which, despite natural induction of Cryab also died at 1 month, transgenic overexpression of Cryab resulted in a markedly reduced CNS stress response, restored expression of the glutamate transporter Glt1 (SLC1A2; <a href="/entry/600300">600300</a>), and protected these animals from death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19129171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 multigeneration French family with autosomal dominant alpha-B crystallin-related myofibrillar myopathy (<a href="/entry/608810">608810</a>) and cataracts reported by <a href="#7" class="mim-tip-reference" title="Fardeau, M., Godet-Guillain, J., Tome, F. M., Collin, H., Gardeau, S., Boffety, C., Vernant, P. <strong>Une nouvelle affection musculaire familiale, definie par l'accumulation intra-sarco-plasmique d'un materiel granulo-filamenta ire dense en microscopie electronique.</strong> Rev. Neurol. 134: 411-425, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/570292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">570292</a>]" pmid="570292">Fardeau et al. (1978)</a>, <a href="#36" class="mim-tip-reference" title="Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M.-C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.-M., Paulin, D., Fardeau, M. <strong>A missense mutation in the alpha-B-crystallin chaperone gene causes a desmin-related myopathy.</strong> Nature Genet. 20: 92-95, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731540</a>] [<a href="https://doi.org/10.1038/1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731540">Vicart et al. (1998)</a> identified a heterozygous 3787A-G transition in the CRYAB gene, resulting in an arg120-to-gly (R120G) substitution. Functional expression studies in muscle cells showed that the R120G mutation resulted in the presence of cytoplasmic or perinuclear alpha-beta-crystallin-labeled aggregates in 80 to 90% of the cells. Desmin-labeled aggregates were also detected. Ultrastructural analysis showed that each aggregate had an inner dense core surrounded by 10-nm intermediate filaments that appeared to engulf the dense deposit. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=570292+9731540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fu, L., Liang, J. J.-N. <strong>Alteration of protein-protein interactions of congenital cataract crystallin mutants.</strong> Invest. Ophthal. Vis. Sci. 44: 1155-1159, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601044</a>]" pmid="12601044">Fu and Liang (2003)</a> observed that alpha-B-crystallin carrying the R120G mutation had decreased interactions with wildtype alpha-A- (<a href="/entry/123580">123580</a>) and alpha-B-crystallins, but slightly increased interactions with wildtype beta-B2- (<a href="/entry/123620">123620</a>) and gamma-C- (<a href="/entry/123680">123680</a>) crystallins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Chavez Zobel, A. T., Loranger, A., Marceau, N., Theriault, J. R., Lambert, H., Landry, J. <strong>Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alpha-B-crystallin mutant.</strong> Hum. Molec. Genet. 12: 1609-1620, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12812987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12812987</a>] [<a href="https://doi.org/10.1093/hmg/ddg173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12812987">Chavez Zobel et al. (2003)</a> reported that the R120G mutant protein has impaired in vivo function and structure, as reflected by a highly reduced capacity to protect cells against heat shock and by an abnormal supramolecular organization even in cells not expressing desmin. In many cells, the mutant protein accumulated in inclusion bodies that had characteristics of aggresomes concentrating around the centrosome. Three distinct chaperone mechanisms could reduce or even prevent the formation of these aggresomes: wildtype alpha-B crystallin and HSP27 (<a href="/entry/602195">602195</a>) prevented aggresome formation by co-oligomerizing with the R120G mutant; HSP70 (see <a href="/entry/140550">140550</a>) with its cochaperone HDJ1 or CHIP (<a href="/entry/607207">607207</a>) reduced the frequency of aggresome formation, likely by targeting the mutant protein for degradation; and HSPB8 (<a href="/entry/608014">608014</a>) interacted only transiently with alpha-B but nonetheless rescued the R120G protein oligomeric organization. <a href="#3" class="mim-tip-reference" title="Chavez Zobel, A. T., Loranger, A., Marceau, N., Theriault, J. R., Lambert, H., Landry, J. <strong>Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alpha-B-crystallin mutant.</strong> Hum. Molec. Genet. 12: 1609-1620, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12812987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12812987</a>] [<a href="https://doi.org/10.1093/hmg/ddg173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12812987">Chavez Zobel et al. (2003)</a> concluded that the formation of inclusion bodies in alpha-B crystallin R120G-mediated desmin-related myopathy may be due to the misfolding of the mutant protein per se and may be delayed or prevented by expression of the wildtype alpha-B allele or other molecular chaperones, which would explain the adult onset of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12812987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 transfected rat primary cardiomyocytes, <a href="#13" class="mim-tip-reference" title="Inagaki, N., Hayashi, T., Arimura, T., Koga, Y., Takahashi, M., Shibata, H., Teraoka, K., Chikamori, T., Yamashina, A., Kimura, A. <strong>Alpha-B-crystallin mutation in dilated cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 342: 379-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16483541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16483541</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.01.154" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16483541">Inagaki et al. (2006)</a> observed intracellular aggregates of the R120G mutant protein. In mammalian-2-hybrid assays, the mutant showed decreased binding to the heart-specific N2B domain and the adjacent striated muscle-specific I26/I27 domains of titin (TTN; <a href="/entry/188840">188840</a>) compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16483541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 thermal stability assay, <a href="#21" class="mim-tip-reference" title="Makley, L. N., McMenimen, K. A., DeVree, B. T., Goldman, J. W., McGlasson, B. N., Rajagopal, P., Dunyak, B. M., McQuade, T. J., Thompson, A. D., Sunahara, R., Klevit, R. E., Andley, U. P., Gestwicki, J. E. <strong>Pharmacological chaperone for alpha-crystallin partially restores transparency in cataract models.</strong> Science 350: 674-677, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26542570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26542570</a>] [<a href="https://doi.org/10.1126/science.aac9145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26542570">Makley et al. (2015)</a> identified a class of molecules that bind alpha-crystallins (cryAA and cryAB) and reverse their aggregation in vitro. The most promising compound improved lens transparency in mouse models of R49C cryAA (<a href="/entry/123580#0003">123580.0003</a>) and R120G cryAB hereditary cataract. It also partially restored protein solubility in the lenses of aged mice in vivo and in human lenses ex vivo. These findings suggest an approach to treating cataracts by stabilizing alpha-crystallins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26542570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 4-generation family of English descent, <a href="#1" class="mim-tip-reference" title="Berry, V., Francis, P., Reddy, M. A., Collyer, D., Vithana, E., MacKay, I., Dawson, G., Carey, A. H., Moore, A., Bhattacharya, S. S., Quinlan, R. A. <strong>Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.</strong> Am. J. Hum. Genet. 69: 1141-1145, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11577372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11577372</a>] [<a href="https://doi.org/10.1086/324158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11577372">Berry et al. (2001)</a> showed that autosomal dominant posterior polar cataract (CTRCT16; <a href="/entry/613763">613763</a>) was caused by heterozygosity for a 1-bp deletion, 450delA, in the CRYAB gene. The deletion caused a frameshift in codon 150 and produced an aberrant protein consisting of 184 residues. <a href="#1" class="mim-tip-reference" title="Berry, V., Francis, P., Reddy, M. A., Collyer, D., Vithana, E., MacKay, I., Dawson, G., Carey, A. H., Moore, A., Bhattacharya, S. S., Quinlan, R. A. <strong>Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.</strong> Am. J. Hum. Genet. 69: 1141-1145, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11577372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11577372</a>] [<a href="https://doi.org/10.1086/324158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11577372">Berry et al. (2001)</a> suggested that the cataract in this family resulted from an increased tendency of the mutant polypeptide to aggregate and/or from loss of chaperone-like activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11577372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1566402514 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566402514;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=rs1566402514" 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=rs1566402514" 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=RCV000018467 OR RCV003574702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018467, RCV003574702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018467...</a>
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<p>In a patient with alpha-B crystallin-related myofibrillar myopathy (<a href="/entry/608810">608810</a>), <a href="#30" class="mim-tip-reference" title="Selcen, D., Engel, A. G. <strong>Myofibrillar myopathy caused by novel dominant negative alpha-B-crystallin mutations.</strong> Ann. Neurol. 54: 804-810, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681890</a>] [<a href="https://doi.org/10.1002/ana.10767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14681890">Selcen and Engel (2003)</a> identified a 2-bp deletion (464delCT) in the C terminus of the CRYAB gene, resulting in a truncated protein of 162 amino acids instead of the normal 175. The mutation was predicted to impair the ability of CRYAB to inhibit heat-induced protein aggregation of unfolded and denatured proteins, resulting in aberrant accumulation of proteins in muscle fibers. Immunoblots under nondenaturing conditions showed that the mutant protein forms lower than normal molecular mass multimeric complexes with the wildtype protein and exerts a dominant-negative effect. The mutation was not found in 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs104894202 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894202;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=rs104894202" 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=rs104894202" 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=RCV000018468" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018468" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018468</a>
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<p>In a patient with alpha-B crystallin-related myofibrillar myopathy (<a href="/entry/608810">608810</a>), <a href="#30" class="mim-tip-reference" title="Selcen, D., Engel, A. G. <strong>Myofibrillar myopathy caused by novel dominant negative alpha-B-crystallin mutations.</strong> Ann. Neurol. 54: 804-810, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681890</a>] [<a href="https://doi.org/10.1002/ana.10767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14681890">Selcen and Engel (2003)</a> identified a 451C-T transition in the CRYAB gene, resulting in a gln151-to-ter (Q151X) mutation. The mutation results in a truncated protein of 150 amino acids instead of the normal 175. The mutation was predicted to impair the ability of CRYAB to inhibit heat-induced protein aggregation of unfolded and denatured proteins, resulting in aberrant accumulation of proteins in muscle fibers. Immunoblots under nondenaturing conditions showed that the mutant protein forms lower than normal molecular mass multimeric complexes with the wildtype protein and exerts a dominant-negative effect. The mutation was not found in 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MYOPATHY, MYOFIBRILLAR, FATAL INFANTILE HYPERTONIC, ALPHA-B CRYSTALLIN-RELATED</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865141 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865141;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/rs281865141?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=rs281865141" 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=rs281865141" 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=RCV000043523" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000043523" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000043523</a>
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<p>In 8 patients with fatal infantile hypertonic myofibrillar myopathy (<a href="/entry/613869">613869</a>), including 3 reported by <a href="#17" class="mim-tip-reference" title="Lacson, A. G., Seshia, S. S., Sarnat, H. B., Anderson, J., DeGroot, W. R., Chudley, A., Adams, C., Darwish, H. Z., Lowry, R. B., Kuhn, S., Lowry, N. J., Ang, L. C., Gibbings, E., Trevenen, C. L., Johnson, E. S., Hoogstraten, J. <strong>Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian natives.</strong> Can. J. Neurol. Sci. 21: 203-212, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8000975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8000975</a>] [<a href="https://doi.org/10.1017/s0317167100041172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8000975">Lacson et al. (1994)</a>, <a href="#4" class="mim-tip-reference" title="Del Bigio, M. R., Chudley, A. E., Sarnat, H. B., Campbell, C., Goobie, S., Chodirker, B. N., Selcen, D. <strong>Infantile muscular dystrophy in Canadian aboriginals is an alpha-B-crystallinopathy.</strong> Ann. Neurol. 69: 866-871, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21337604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21337604</a>] [<a href="https://doi.org/10.1002/ana.22331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21337604">Del Bigio et al. (2011)</a> identified the same homozygous 1-bp deletion in the CRYAB gene (<a href="#0005">123590.0005</a>), resulting in a ser21-to-ala (S21A) change and a stop codon after 23 missense residues. All patients were Canadian aboriginals of Cree descent, consistent with a founder effect. The phenotype was characterized by onset in the first weeks of life of rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. Muscle biopsies showed dystrophic changes, endomysial fibrosis, eosinophilic deposits, and Z-band streaming. Immunohistochemistry using an antibody against the full-length CRYAB protein showed absence of staining, but an antibody against the first 10 residues of the protein showed some residual staining. Heterozygous parents were unaffected, including 1 mother with mild myopathic symptoms but normal CK levels. <a href="#4" class="mim-tip-reference" title="Del Bigio, M. R., Chudley, A. E., Sarnat, H. B., Campbell, C., Goobie, S., Chodirker, B. N., Selcen, D. <strong>Infantile muscular dystrophy in Canadian aboriginals is an alpha-B-crystallinopathy.</strong> Ann. Neurol. 69: 866-871, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21337604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21337604</a>] [<a href="https://doi.org/10.1002/ana.22331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21337604">Del Bigio et al. (2011)</a> noted that late-onset myofibrillar myopathy (<a href="/entry/608810">608810</a>) is typically seen in heterozygous individuals; however, in this disease, the parental phenotype may be rescued by limited expression of the 44-amino acid truncated nonfunctional gene product. <a href="#4" class="mim-tip-reference" title="Del Bigio, M. R., Chudley, A. E., Sarnat, H. B., Campbell, C., Goobie, S., Chodirker, B. N., Selcen, D. <strong>Infantile muscular dystrophy in Canadian aboriginals is an alpha-B-crystallinopathy.</strong> Ann. Neurol. 69: 866-871, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21337604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21337604</a>] [<a href="https://doi.org/10.1002/ana.22331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21337604">Del Bigio et al. (2011)</a> postulated that a disruption of CRYAB interaction with titin (TTN; <a href="/entry/188840">188840</a>) may contribute to reduced muscle elasticity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8000975+21337604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 CARDIOMYOPATHY, DILATED, 1II</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> rs141638421 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141638421;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/rs141638421?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=rs141638421" 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=rs141638421" 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=RCV000034838 OR RCV002336111 OR RCV002490468" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034838, RCV002336111, RCV002490468" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034838...</a>
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<p>In a 71-year-old Japanese woman with mild, late-onset dilated cardiomyopathy (CMD1II; <a href="/entry/615184">615184</a>), <a href="#13" class="mim-tip-reference" title="Inagaki, N., Hayashi, T., Arimura, T., Koga, Y., Takahashi, M., Shibata, H., Teraoka, K., Chikamori, T., Yamashina, A., Kimura, A. <strong>Alpha-B-crystallin mutation in dilated cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 342: 379-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16483541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16483541</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.01.154" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16483541">Inagaki et al. (2006)</a> identified heterozygosity for a G-A transition in exon 3 of the CRYAB gene, resulting in an arg157-to-his (R157H) substitution at an evolutionarily conserved residue. The patient had 2 sibs with CMD and 2 other sibs who had sudden cardiac death, but DNA was not available for analysis from any family members. The mutation was not found in 400 control chromosomes. Functional analysis showed decreased binding of the R157H mutant to the heart-specific N2B domain of titin (TTN; <a href="/entry/188840">188840</a>) compared to wildtype, without affecting distribution in cardiomyocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16483541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs150516929 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs150516929;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/rs150516929?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=rs150516929" 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=rs150516929" 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=RCV000034839 OR RCV000037217 OR RCV000157153 OR RCV000203359 OR RCV000297606 OR RCV000352488 OR RCV000398508 OR RCV000620796 OR RCV000658624 OR RCV000852658 OR RCV001170406 OR RCV003914912" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034839, RCV000037217, RCV000157153, RCV000203359, RCV000297606, RCV000352488, RCV000398508, RCV000620796, RCV000658624, RCV000852658, RCV001170406, RCV003914912" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034839...</a>
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<p>In a 48-year-old woman with mild, late-onset dilated cardiomyopathy (CMD1II; <a href="/entry/615184">615184</a>), <a href="#25" class="mim-tip-reference" title="Pilotto, A., Marziliano, N., Pasotti, M., Grasso, M., Costante, A. M., Arbustini, E. <strong>Alpha-B-crystallin mutation in dilated cardiomyopathies: low prevalence in a consecutive series of 200 unrelated probands.</strong> Biochem. Biophys. Res. Commun. 346: 1115-1117, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16793013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16793013</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.05.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16793013">Pilotto et al. (2006)</a> identified heterozygosity for a G-A transition in the CRYAB gene, resulting in a gly154-to-ser (G154S) substitution at an evolutionarily conserved residue. DNA was unavailable from her father, who died at age 80 after a 20-year history of congestive heart failure due to CMD; the mutation was not found in 200 controls. The patient had a minimal increase in serum CPK, suggestive of possible subclinical muscle involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16793013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CATARACT 16, CONGENITAL LAMELLAR</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">rs387907336 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907336;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=rs387907336" 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=rs387907336" 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=RCV000034840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034840</a>
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<p>In 4 affected members of a large 5-generation Chinese family with congenital lamellar cataract (CTRCT16; <a href="/entry/613763">613763</a>), <a href="#20" class="mim-tip-reference" title="Liu, Y., Zhang, X., Luo, L., Wu, M., Zeng, R., Cheng, G., Hu, B., Liu, B., Liang, J. J., Shang, F. <strong>A novel alpha-B-crystallin mutation associated with autosomal dominant congenital lamellar cataract.</strong> Invest. Ophthal. Vis. Sci. 47: 1069-1075, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505043</a>] [<a href="https://doi.org/10.1167/iovs.05-1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16505043">Liu et al. (2006)</a> identified heterozygosity for a G-A transition in exon 3 of the CRYAB gene, resulting in an asp140-to-asn (D140N) substitution within the highly conserved alpha-crystallin domain. The mutation was not found in 5 unaffected members of the family or in 100 controls. In functional analyses, the mutant alpha-B crystallin showed abnormal oligomerization, reduced thermal stability, and abolished chaperone-like activity. In addition, the D140N mutant acted as a dominant negative, interfering with the chaperone-like activity of wildtype alpha-B crystallin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CATARACT 16, POSTERIOR POLAR</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">rs387907337 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907337;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=rs387907337" 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=rs387907337" 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=RCV000034841" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034841" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034841</a>
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<p>In 13 affected members of a 4-generation Chinese family with congenital posterior polar cataract (CTRCT16; <a href="/entry/613763">613763</a>), <a href="#19" class="mim-tip-reference" title="Liu, M., Ke, T., Wang, Z., Yang, Q., Chang, W., Jiang, F., Tang, Z., Li, H., Ren, X., Wang, X., Wang, T., Li, Q., Yang, J., Liu, J., Wang, Q. K. <strong>Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family.</strong> Invest. Ophthal. Vis. Sci. 47: 3461-3466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16877416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16877416</a>] [<a href="https://doi.org/10.1167/iovs.05-1438" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16877416">Liu et al. (2006)</a> identified heterozygosity for a 58C-T transition in exon 1 of the CRYAB gene, resulting in a pro20-to-ser (P20S) substitution at a highly conserved residue in the N-terminal region of alpha-B crystallin. The mutation was not found in 8 unaffected family members or in 200 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16877416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 CATARACT, JUVENILE</strong>
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CRYAB, ARG56TRP
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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> rs387907338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907338;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/rs387907338?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=rs387907338" 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=rs387907338" 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=RCV000034842 OR RCV001852700 OR RCV003984812 OR RCV004018734" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034842, RCV001852700, RCV003984812, RCV004018734" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034842...</a>
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<p>In an affected mother and her 4 affected children from a consanguineous Saudi Arabian family with juvenile cataract (CTRCT16; <a href="/entry/613763">613763</a>), <a href="#29" class="mim-tip-reference" title="Safieh, L. A., Khan, A. O., Alkuraya, F. S. <strong>Identification of a novel CRYAB mutation associated with autosomal recessive juvenile cataract in a Saudi family.</strong> Molec. Vis. 15: 980-984, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19461931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19461931</a>]" pmid="19461931">Safieh et al. (2009)</a> identified homozygosity for a 166C-T transition in exon 1 of the CRYAB gene, resulting in an arg56-to-trp (R56W) substitution at a highly conserved residue. The unaffected father was heterozygous for the mutation, which was not found in 150 Saudi controls. The 35-year-old mother also had retinal dystrophic changes; <a href="#29" class="mim-tip-reference" title="Safieh, L. A., Khan, A. O., Alkuraya, F. S. <strong>Identification of a novel CRYAB mutation associated with autosomal recessive juvenile cataract in a Saudi family.</strong> Molec. Vis. 15: 980-984, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19461931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19461931</a>]" pmid="19461931">Safieh et al. (2009)</a> noted that it was unclear whether the retinal phenotype was related to the CRYAB mutation or due to another cause. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19461931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>.0011 MYOPATHY, MYOFIBRILLAR, 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387907339 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907339;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/rs387907339?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=rs387907339" 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=rs387907339" 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=RCV000034843" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034843" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034843</a>
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<p>In all affected members of a family of North African origin with myofibrillar myopathy, posterior polar cataract, and dilated cardiomyopathy (<a href="/entry/608810">608810</a>), <a href="#28" class="mim-tip-reference" title="Sacconi, S., Feasson, L., Antoine, J. C., Pecheux, C., Bernard, R., Cobo, A. M., Casarin, A., Salviati, L., Desnuelle, C., Urtizberea, A. <strong>A novel CRYAB mutation resulting in multisystemic disease.</strong> Neuromusc. Disord. 22: 66-72, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21920752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21920752</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.07.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21920752">Sacconi et al. (2012)</a> identified heterozygosity for a 325G-C transversion in exon 3 of the CRYAB gene, resulting in an asp109-to-his (D109H) substitution at a conserved residue involved in dimerization of the protein. The mutation was not found in unaffected family members or in 50 ethnically matched controls. Molecular modeling indicated that D109 interacts with R120 on the opposite alpha-B crystallin monomer during dimerization; <a href="#28" class="mim-tip-reference" title="Sacconi, S., Feasson, L., Antoine, J. C., Pecheux, C., Bernard, R., Cobo, A. M., Casarin, A., Salviati, L., Desnuelle, C., Urtizberea, A. <strong>A novel CRYAB mutation resulting in multisystemic disease.</strong> Neuromusc. Disord. 22: 66-72, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21920752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21920752</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.07.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21920752">Sacconi et al. (2012)</a> noted that R120 was previously found to be mutated in a French family with a similar phenotype involving myofibrillar myopathy, cardiomyopathy, and cataract (R120G; <a href="#0001">123590.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21920752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Quax-Jeuken1985" class="mim-tip-reference" title="Quax-Jeuken, Y., Quax, W., van Rens, G., Meera Khan, P., Bloemendal, H. <strong>Complete structure of the alpha-B-crystallin gene: conservation of the exon-intron distribution in the two nonlinked alpha-crystallin genes.</strong> Proc. Nat. Acad. Sci. 82: 5819-5823, 1985.">Quax-Jeuken et al. (1985)</a>; <a href="#Rappaport1988" class="mim-tip-reference" title="Rappaport, L., Contard, F., Samuel, J. L., Delcayre, C., Marotte, F., Tome, F., Fardeau, M. <strong>Storage of phosphorylated desmin in a familial myopathy.</strong> FEBS Lett. 231: 421-425, 1988.">Rappaport et al. (1988)</a>; <a href="#Vicart1996" class="mim-tip-reference" title="Vicart, P., Dupret, J.-M., Hazan, J., Li, Z., Gyapay, G., Krishnamoorthy, R., Weissenbach, J., Fardeau, M., Paulin, D. <strong>Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy.</strong> Hum. Genet. 98: 422-429, 1996.">Vicart et al.
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[<a href="https://doi.org/10.1093/hmg/ddg173" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1167/iovs.03-0720" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp013" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14610128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14610128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14610128" 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/10.1212/01.wnl.0000091861.27246.9e" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="36" class="mim-anchor"></a>
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<a id="Vicart1998" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
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|
Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M.-C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.-M., Paulin, D., Fardeau, M.
|
|
<strong>A missense mutation in the alpha-B-crystallin chaperone gene causes a desmin-related myopathy.</strong>
|
|
Nature Genet. 20: 92-95, 1998.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731540" 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/10.1038/1765" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="37" class="mim-anchor"></a>
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<a id="Vicart1996" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Vicart, P., Dupret, J.-M., Hazan, J., Li, Z., Gyapay, G., Krishnamoorthy, R., Weissenbach, J., Fardeau, M., Paulin, D.
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|
<strong>Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy.</strong>
|
|
Hum. Genet. 98: 422-429, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8792816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8792816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8792816" 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/s004390050233" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="38" class="mim-anchor"></a>
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<a id="Wang2005" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Wang, J., Xu, G., Li, H., Gonzales, V., Fromholt, D., Karch, C., Copeland, N. G., Jenkins N. A., Borchelt, D. R.
|
|
<strong>Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates degeneration: alpha-B-crystallin modulates aggregation.</strong>
|
|
Hum. Molec. Genet. 14: 2335-2347, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16000321" 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/ddi236" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="39" class="mim-anchor"></a>
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<a id="Yamashita2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Yamashita, A., Taniwaki, T., Kaikoi, Y., Yamazaki, T.
|
|
<strong>Protective role of the endoplasmic reticulum protein mitsugumin23 against ultraviolet C-induced cell death.</strong>
|
|
FEBS Lett. 587: 1299-1303, 2013.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23542032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23542032</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23542032" 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.febslet.2013.03.024" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Elizabeth S. Partan - updated : 01/28/2021
|
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</span>
|
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Ada Hamosh - updated : 09/15/2016<br>Ada Hamosh - updated : 1/5/2015<br>Marla J. F. O'Neill - updated : 6/12/2013<br>Marla J. F. O'Neill - updated : 4/18/2013<br>Ada Hamosh - updated : 4/9/2012<br>Cassandra L. Kniffin - updated : 4/5/2011<br>George E. Tiller - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 5/22/2008<br>Ada Hamosh - updated : 8/20/2007<br>Patricia A. Hartz - updated : 3/28/2006<br>George E. Tiller - updated : 4/26/2005<br>Cassandra L. Kniffin - reorganized : 7/23/2004<br>Cassandra L. Kniffin - updated : 7/22/2004<br>Jane Kelly - updated : 6/14/2004<br>Jane Kelly - updated : 3/4/2004<br>Cassandra L. Kniffin - updated : 2/5/2004<br>Victor A. McKusick - updated : 11/27/2001<br>Victor A. McKusick - updated : 8/28/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
|
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 02/21/2023
|
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</span>
|
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
mgross : 01/28/2021<br>carol : 12/03/2020<br>alopez : 09/15/2016<br>carol : 06/23/2016<br>alopez : 1/5/2015<br>carol : 8/7/2013<br>carol : 6/12/2013<br>carol : 4/18/2013<br>carol : 8/28/2012<br>alopez : 4/9/2012<br>terry : 4/9/2012<br>terry : 6/23/2011<br>wwang : 4/22/2011<br>wwang : 4/12/2011<br>ckniffin : 4/7/2011<br>wwang : 4/7/2011<br>ckniffin : 4/5/2011<br>carol : 2/22/2011<br>wwang : 11/10/2009<br>terry : 10/27/2009<br>wwang : 1/9/2009<br>wwang : 5/23/2008<br>ckniffin : 5/22/2008<br>alopez : 8/31/2007<br>terry : 8/20/2007<br>carol : 12/15/2006<br>carol : 11/30/2006<br>wwang : 4/4/2006<br>terry : 3/28/2006<br>tkritzer : 4/26/2005<br>carol : 7/23/2004<br>ckniffin : 7/22/2004<br>alopez : 6/14/2004<br>mgross : 3/17/2004<br>alopez : 3/5/2004<br>alopez : 3/5/2004<br>alopez : 3/4/2004<br>tkritzer : 2/12/2004<br>ckniffin : 2/5/2004<br>alopez : 12/3/2001<br>terry : 11/27/2001<br>dkim : 9/10/1998<br>alopez : 8/31/1998<br>terry : 8/28/1998<br>terry : 8/24/1998<br>alopez : 4/13/1998<br>terry : 12/5/1996<br>terry : 7/10/1995<br>mark : 6/28/1995<br>carol : 2/25/1993<br>supermim : 3/16/1992<br>carol : 9/14/1990<br>carol : 8/23/1990
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 123590
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CRYSTALLIN, ALPHA-B; CRYAB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CRYSTALLIN, ALPHA-2; CRYA2<br />
|
|
HEAT-SHOCK PROTEIN BETA-5; HSPB5
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
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<br />
|
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</div>
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</div>
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|
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: CRYAB</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 399336001, 782883004;
|
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</span>
|
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</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 11q23.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:111,908,564-111,923,740 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
11q23.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1II
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615184
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Cataract 16, multiple types
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613763
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myopathy, myofibrillar, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
608810
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613869
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The crystallins compose approximately 90% of the soluble protein of the vertebrate eye lens and include 3 major families of ubiquitously expressed crystallins: alpha (e.g., CRYAA; 123580), beta (e.g., CRYBA1; 123610), and gamma (e.g., CRYGA; 123660). Alpha-B-crystallin is a member of the small heat-shock protein family (Dubin et al., 1990). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
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|
<p>Dubin et al. (1990) presented the complete nucleotide sequence of the human CRYAB gene, which encodes a 175-amino acid protein with a molecular mass of 20 kD. </p><p>In the mouse, Dubin et al. (1989) found that the Cryab gene is expressed in the lens, heart, skeletal muscle, kidney, and lung. In the rat, Iwaki et al. (1990) found Cryab expression in lens, iris, heart, skeletal muscle, certain regions of the kidney, Schwann cells of peripheral nerves, glia in the central nervous system, and decidual cells of the placenta. </p><p>By functional analysis of a CRYAB promoter fragment fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, Dubin et al. (1990) found that the fragment contains regulatory elements that function predominantly, but not exclusively, in lens. Although alpha-B-crystallin had been reported to accumulate in brain cells in Alexander disease (203450) (Iwaki et al., 1989), Dubin et al. (1990) found that the promoter fragment was insufficient to promote transcription in a glial cell line that synthesizes high levels of the endogenous CRYAB gene product. </p>
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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>Dubin et al. (1990) determined that the CRYAB gene contains 3 exons. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>By use of a CRYA2 genomic probe in connection with mouse-human somatic cell hybrid DNA, Ngo et al. (1989) assigned the gene to chromosome 11; by in situ hybridization, they regionalized the locus to 11q22.3-q23.1. </p><p>By study of a panel of human/rodent hybrid cell lines using a probe consisting of the third exon of the hamster alpha-B-crystallin gene, Brakenhoff et al. (1990) assigned the CRYA2 gene to chromosome 11. Using cell hybrids containing translocated and/or partially deleted human chromosome 11, they localized the CRYA2 gene further to 11q12-q23. Jeanpierre et al. (1993) showed that the CRYA2 gene lies proximal to the 11q23.2 breakpoint defined by the constitutional t(11;22) and distal to the 11q22.1 breakpoint of a constitutional interstitial deletion. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Atomic Structure</em></strong></p><p>
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Laganowsky et al. (2012) identified a segment of the amyloid-forming protein alpha-B crystallin that forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer revealed a cylindrical barrel, formed from 6 antiparallel protein strands, which Laganowsky et al. (2012) termed a cylindrin. The cylindrin structure is compatible with a sequence segment from the beta-amyloid protein of Alzheimer disease. Laganowsky et al. (2012) concluded that cylindrins offer models for the hitherto elusive structures of amyloid oligomers. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Van Noort et al. (1995) examined proliferative responses of human peripheral blood T cells to the complete collection of myelin proteins, including alpha-B-crystallin. They found that alpha-B-crystallin was a highly immunogenic protein to which T cells from multiple sclerosis (MS; 126200) patients and from healthy controls showed dominant responses. Immunohistochemical examination of MS lesions revealed the presence of oligodendrocytes and astrocytes with raised CRYA2 expression, which was not found in unaffected myelin, suggesting that the CRYA2 protein may be an autoantigen in MS. The authors noted that alpha-B-crystallin had been detected in brains of patients with other neurologic diseases, including Alzheimer (104300), Parkinson (168600, 168601), Pick (172700), and Huntington (143100) diseases. Steinman (1995) discussed the significance of the immune reaction against alpha-B-crystallin in the pathology of MS. </p><p>The alpha-crystallin subunits alpha-A and alpha-B each can form an oligomer by itself or with the other. Fu and Liang (2002) used a 2-hybrid system to study heterogeneous interactions among lens crystallins of different classes. They found interactions between alpha-A- (or alpha-B-) and beta-B2- or gamma-C- (123680)-crystallins, but the intensity of interaction was one-third that of alpha-A-alpha-B interactions. HSP27 (602195), a member of the small heat-shock protein family, showed similar interaction properties with alpha-B-crystallin. Experiments with N- and C-terminal domain-truncated mutants demonstrated that both N- and C-terminal domains were important in alpha-A-crystallin self-interaction, but that only the C-terminal domain was important in alpha-B-crystallin self-interaction. </p><p>Cataractogenesis (development of lens opacity) is believed to be a consequence of accumulation of insoluble aggregates and gross-linked products of alpha-, beta-, and gamma-crystallins. The insolubilization of crystallins is thought to be initiated by posttranslational modifications that change their structural and functional properties. Srivastava and Srivastava (2003) showed that the asparagine-146 residue (N146) of human alpha-B-crystallin undergoes in vivo deamidation, and several fragments containing this modification were found in both water-soluble and -insoluble protein fractions of normal and cataractous human lenses. Gupta and Srivastava (2004) showed that deamidation of N146 but not of N78 of CRYAB had profound effects on the structural and functional properties of alpha-B-crystallin. </p><p>By immunohistochemical analysis, Moyano et al. (2006) found that CRYAB was expressed in 18 (45%) of 40 basal-like breast tumors and predicted poor survival of breast cancer patients independently of other prognostic markers. Overexpression of CRYAB transformed immortalized human mammary epithelial cells (MECs) and conferred neoplastic-like changes, which were suppressed by MEK (see MAP2K1; 176872) inhibitors. Immortalized human MECs overexpressing CRYAB formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. </p><p>Wang et al. (2005) found that in SOD1 (147450)-mutant mouse cells alpha-B-crystallin suppressed aggregation of mutant SOD1 in somatodendritic compartments. In vivo, alpha-B-crystallin immunoreactivity was most abundant in oligodendrocytes and upregulated in astrocytes of symptomatic mice; neither of these cell types accumulated mutant SOD1 immunoreactivity. Wang et al. (2005) suggested that damage to motor neuron cell bodies and dendrites within the spinal cord may be sufficient to induce motor neuron disease, and that activities of chaperones may modulate the cellular specificity of mutant SOD1 accumulation. </p><p>Shao et al. (2013) showed that the astrocytic dopamine D2 receptor (DRD2; 126450) modulates innate immunity through CRYAB, which is known to suppress inflammation. Shao et al. (2013) demonstrated that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Drd2-null astrocytes became hyperresponsive to immune stimuli, with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wildtype mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Shao et al. (2013) concluded that their study indicated that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provided a strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during aging and disease. </p><p>Yamashita et al. (2013) found that knockdown of the endoplasmic reticulum (ER) protein TMEM109 (619168) in HEK293T cells caused a 15% increase in apoptosis in response to ultraviolet C (UVC) irradiation compared with controls. Conversely, overexpression of mouse Tmem109 improved cell survival following UVC irradiation. The UVC sensitivity phenotype required the second cytoplasmic region (CP2) of TMEM109. Yeast 2-hybrid and coimmunoprecipitation assays showed that the CP2 region of mouse Tmem109 interacted with the C-terminal half of human CRYAB. The extent of UVC-induced cell death in TMEM109-knockdown, CRYAB-knockdown, and TMEM109/CRYAB dual-knockdown cells was equivalent, suggesting that TMEM109 and CRYAB function together rather than in parallel. A fusion protein of full-length human CRYAB and the first transmembrane domain of mouse Tmem109, which was predicted to anchor to the ER, also increased UVC resistance, suggesting that TMEM109 protects against UVC by accumulating CRYAB near the ER. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Myofibrillar Myopathy 2</em></strong></p><p>
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In affected members of a family with an autosomal dominant myofibrillar myopathy (MFM2; 608810) reported by Fardeau et al. (1978), Vicart et al. (1998) identified a heterozygous mutation in the CRYAB gene (123590.0001). Affected individuals also exhibited clinical or electrocardiographic signs of hypertrophic cardiomyopathy and discrete lens opacities. </p><p>In 2 unrelated patients with myofibrillar myopathy, Selcen and Engel (2003) identified 2 different heterozygous mutations in the CRYAB gene (123590.0003; 123590.0004). Expression studies of both mutations were consistent with a dominant-negative effect. </p><p>By in vitro experiments using different CRYAB mutants, Hayes et al. (2008) found that the C-terminal extension was important for oligomerization. The Q151X mutation (123590.0004) decreased oligomerization and even increased some chaperone activities, but it also significantly destabilized the protein and caused self-aggregation. The 450delA (123590.0002) and 464delCT (123590.0003) mutants could only be refolded and assayed as a complex with wildtype CRYAB. Hayes et al. (2008) concluded that mutations in the C-terminal extension destabilize the protein and increase its tendency to self-aggregate. It is this tendency, rather than a loss of chaperone activity, that is the major pathogenic factor. </p><p>In all affected members of a family of North African origin with myofibrillar myopathy, posterior polar cataract, and dilated cardiomyopathy, Sacconi et al. (2012) identified heterozygosity for a missense mutation in the CRYAB gene (D109H; 123590.0011). The mutation was not found in unaffected family members or 50 ethnically matched controls. </p><p><strong><em>Fatal Infantile Hypertonic Myofibrillar Myopathy</em></strong></p><p>
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In 8 patients with fatal infantile hypertonic myofibrillar myopathy (613869), Del Bigio et al. (2011) identified the same homozygous 1-bp deletion in the CRYAB gene (60delC; 123590.0005). All patients were Canadian aboriginals of Cree descent, consistent with a founder effect. The phenotype was characterized by onset in the first weeks of life of rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. </p><p><strong><em>Cataract 16, Multiple Types</em></strong></p><p>
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In a 4-generation family of English descent with autosomal dominant congenital posterior polar cataracts (CTRCT16; 613763), Berry et al. (2001) identified a deletion mutation in the CRYAB gene (123590.0002). </p><p>Fu and Liang (2003) studied the effect of crystallin gene mutations that result in congenital cataract on protein-protein interactions. Interactions between mutated crystallins alpha-A (R116C; 123580.0001), alpha-B (R120G; 123590.0001), and gamma-C (T5P; 123680.0001) and the corresponding wildtype proteins, as well as with wildtype beta-B2-crystallin (123620) and HSP27, were analyzed in a mammalian cell 2-hybrid system. For mutated alpha-A-crystallin, interactions with wildtype beta-B2-crystallin and gamma-C-crystallin decreased and those with wildtype alpha-B-crystallin and HSP27 increased. For mutated alpha-B-crystallin, interactions with wildtype alpha-A-crystallin and alpha-B-crystallin decreased, but those with wildtype beta-B2-crystallin and gamma-C-crystallin increased slightly. For mutated gamma-C-crystallin, most of the interactions were decreased. The results indicated that crystallin mutations involved in congenital cataracts altered protein-protein interactions, which might contribute to decreased protein solubility and formation of cataract. </p><p>In affected members of large 5-generation Chinese family with congenital lamellar cataract who were negative for mutation at known hotspots in 9 cataract-associated genes, Liu et al. (2006) identified heterozygosity for a missense mutation in CRYAB (D140N; 123590.0008) that segregated with disease and was not found in 100 controls. </p><p>In a 4-generation Chinese family with congenital posterior polar cataract mapping to 11q22, Liu et al. (2006) identified a heterozygous missense mutation in the CRYAB gene (P20S; 123590.0009) that segregated fully with disease in the family and was not found in 200 controls. </p><p>In an affected mother and 4 affected children from a consanguineous Saudi family with cataract mapping to 11q21-q23, Safieh et al. (2009) identified homozygosity for a missense mutation in the CRYAB gene (R56W; 123590.0010). The unaffected father was heterozygous for the mutation, which was not found in 150 Saudi controls. </p><p><strong><em>Cardiomyopathy, Dilated, 1II</em></strong></p><p>
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Inagaki et al. (2006) analyzed the CRYAB gene in 130 unrelated Japanese patients with dilated cardiomyopathy (CMD1II; 615184) who were negative for mutations in known CMD genes, and identified a heterozygous missense mutation (R157H; 123590.0006) in a 71-year-old woman with mild, late-onset disease. </p><p>Pilotto et al. (2006) screened the CRYAB gene in 200 consecutive patients diagnosed with autosomal dominant or sporadic CMD, and identified a heterozygous missense mutation (G154S; 123590.0007) in a 48-year-old woman with recently diagnosed CMD. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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Van Veen et al. (2003) presented evidence suggesting that polymorphisms in the promoter region of the CRYAB gene may influence the clinical phenotype of multiple sclerosis (126200). </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>Alpha-B-crystallin is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has antiapoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T cell immunity to the myelin sheath from multiple sclerosis brain. Ousman et al. (2007) demonstrated that CRYAB is a potent negative regulator acting as a brake on several inflammatory pathways in both the immune system and central nervous system. Cryab-null mice showed worse experimental autoimmune encephalomyelitis at the acute and progressive phases, with higher Th1 and Th17 cytokine secretion from T cells and macrophages, and more intense central nervous system (CNS) inflammation, compared with their wildtype counterparts. Furthermore, Cryab-null astrocytes showed more cleaved caspase-3 (600636) and more TUNEL staining, indicating an antiapoptotic function of Cryab. </p><p>Alexander disease is a primary disorder of astrocytes caused by dominant mutations in the gene for glial fibrillary acidic protein (GFAP; 137780). These mutations lead to protein aggregation and formation of Rosenthal fibers, complex astrocytic inclusions that contain GFAP, vimentin (VIM; 193060), plectin (PLEC1; 601282), ubiquitin (UBB; 191339), Hsp27, and CRYAB. CRYAB regulates GFAP assembly, and elevation of CRYAB is a consistent feature of Alexander disease; however, its role in Rosenthal fibers and disease pathology is not known. In a mouse model of Alexander disease, Hagemann et al. (2009) showed that loss of Cryab resulted in increased mortality, whereas elevation of Cryab rescued animals from terminal seizures. When mice with Rosenthal fibers induced by overexpression of GFAP were crossed into a Cryab-null background, over half died at 1 month of age. Restoration of Cryab expression through the GFAP promoter reversed this outcome, showing the effect was astrocyte-specific. Conversely, in mice carrying an Alexander disease-associated mutation and in mice overexpressing wildtype GFAP, which, despite natural induction of Cryab also died at 1 month, transgenic overexpression of Cryab resulted in a markedly reduced CNS stress response, restored expression of the glutamate transporter Glt1 (SLC1A2; 600300), and protected these animals from death. </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>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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MYOPATHY, MYOFIBRILLAR, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRYAB, ARG120GLY
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<br />
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SNP: rs104894201,
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ClinVar: RCV000018465
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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 multigeneration French family with autosomal dominant alpha-B crystallin-related myofibrillar myopathy (608810) and cataracts reported by Fardeau et al. (1978), Vicart et al. (1998) identified a heterozygous 3787A-G transition in the CRYAB gene, resulting in an arg120-to-gly (R120G) substitution. Functional expression studies in muscle cells showed that the R120G mutation resulted in the presence of cytoplasmic or perinuclear alpha-beta-crystallin-labeled aggregates in 80 to 90% of the cells. Desmin-labeled aggregates were also detected. Ultrastructural analysis showed that each aggregate had an inner dense core surrounded by 10-nm intermediate filaments that appeared to engulf the dense deposit. </p><p>Fu and Liang (2003) observed that alpha-B-crystallin carrying the R120G mutation had decreased interactions with wildtype alpha-A- (123580) and alpha-B-crystallins, but slightly increased interactions with wildtype beta-B2- (123620) and gamma-C- (123680) crystallins. </p><p>Chavez Zobel et al. (2003) reported that the R120G mutant protein has impaired in vivo function and structure, as reflected by a highly reduced capacity to protect cells against heat shock and by an abnormal supramolecular organization even in cells not expressing desmin. In many cells, the mutant protein accumulated in inclusion bodies that had characteristics of aggresomes concentrating around the centrosome. Three distinct chaperone mechanisms could reduce or even prevent the formation of these aggresomes: wildtype alpha-B crystallin and HSP27 (602195) prevented aggresome formation by co-oligomerizing with the R120G mutant; HSP70 (see 140550) with its cochaperone HDJ1 or CHIP (607207) reduced the frequency of aggresome formation, likely by targeting the mutant protein for degradation; and HSPB8 (608014) interacted only transiently with alpha-B but nonetheless rescued the R120G protein oligomeric organization. Chavez Zobel et al. (2003) concluded that the formation of inclusion bodies in alpha-B crystallin R120G-mediated desmin-related myopathy may be due to the misfolding of the mutant protein per se and may be delayed or prevented by expression of the wildtype alpha-B allele or other molecular chaperones, which would explain the adult onset of the disease. </p><p>In transfected rat primary cardiomyocytes, Inagaki et al. (2006) observed intracellular aggregates of the R120G mutant protein. In mammalian-2-hybrid assays, the mutant showed decreased binding to the heart-specific N2B domain and the adjacent striated muscle-specific I26/I27 domains of titin (TTN; 188840) compared to wildtype. </p><p>Using a thermal stability assay, Makley et al. (2015) identified a class of molecules that bind alpha-crystallins (cryAA and cryAB) and reverse their aggregation in vitro. The most promising compound improved lens transparency in mouse models of R49C cryAA (123580.0003) and R120G cryAB hereditary cataract. It also partially restored protein solubility in the lenses of aged mice in vivo and in human lenses ex vivo. These findings suggest an approach to treating cataracts by stabilizing alpha-crystallins. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CATARACT 16, POSTERIOR POLAR</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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CRYAB, 1-BP DEL, 450A
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<br />
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SNP: rs1566402656,
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ClinVar: RCV000018466
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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 4-generation family of English descent, Berry et al. (2001) showed that autosomal dominant posterior polar cataract (CTRCT16; 613763) was caused by heterozygosity for a 1-bp deletion, 450delA, in the CRYAB gene. The deletion caused a frameshift in codon 150 and produced an aberrant protein consisting of 184 residues. Berry et al. (2001) suggested that the cataract in this family resulted from an increased tendency of the mutant polypeptide to aggregate and/or from loss of chaperone-like activity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MYOPATHY, MYOFIBRILLAR, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRYAB, 2-BP DEL, 464CT
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<br />
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SNP: rs1566402514,
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ClinVar: RCV000018467, RCV003574702
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with alpha-B crystallin-related myofibrillar myopathy (608810), Selcen and Engel (2003) identified a 2-bp deletion (464delCT) in the C terminus of the CRYAB gene, resulting in a truncated protein of 162 amino acids instead of the normal 175. The mutation was predicted to impair the ability of CRYAB to inhibit heat-induced protein aggregation of unfolded and denatured proteins, resulting in aberrant accumulation of proteins in muscle fibers. Immunoblots under nondenaturing conditions showed that the mutant protein forms lower than normal molecular mass multimeric complexes with the wildtype protein and exerts a dominant-negative effect. The mutation was not found in 200 control chromosomes. </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>.0004 MYOPATHY, MYOFIBRILLAR, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRYAB, GLN151TER
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<br />
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SNP: rs104894202,
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ClinVar: RCV000018468
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with alpha-B crystallin-related myofibrillar myopathy (608810), Selcen and Engel (2003) identified a 451C-T transition in the CRYAB gene, resulting in a gln151-to-ter (Q151X) mutation. The mutation results in a truncated protein of 150 amino acids instead of the normal 175. The mutation was predicted to impair the ability of CRYAB to inhibit heat-induced protein aggregation of unfolded and denatured proteins, resulting in aberrant accumulation of proteins in muscle fibers. Immunoblots under nondenaturing conditions showed that the mutant protein forms lower than normal molecular mass multimeric complexes with the wildtype protein and exerts a dominant-negative effect. The mutation was not found in 200 control chromosomes. </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>.0005 MYOPATHY, MYOFIBRILLAR, FATAL INFANTILE HYPERTONIC, ALPHA-B CRYSTALLIN-RELATED</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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CRYAB, 1-BP DEL, 60C
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<br />
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SNP: rs281865141,
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gnomAD: rs281865141,
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ClinVar: RCV000043523
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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 8 patients with fatal infantile hypertonic myofibrillar myopathy (613869), including 3 reported by Lacson et al. (1994), Del Bigio et al. (2011) identified the same homozygous 1-bp deletion in the CRYAB gene (123590.0005), resulting in a ser21-to-ala (S21A) change and a stop codon after 23 missense residues. All patients were Canadian aboriginals of Cree descent, consistent with a founder effect. The phenotype was characterized by onset in the first weeks of life of rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. Muscle biopsies showed dystrophic changes, endomysial fibrosis, eosinophilic deposits, and Z-band streaming. Immunohistochemistry using an antibody against the full-length CRYAB protein showed absence of staining, but an antibody against the first 10 residues of the protein showed some residual staining. Heterozygous parents were unaffected, including 1 mother with mild myopathic symptoms but normal CK levels. Del Bigio et al. (2011) noted that late-onset myofibrillar myopathy (608810) is typically seen in heterozygous individuals; however, in this disease, the parental phenotype may be rescued by limited expression of the 44-amino acid truncated nonfunctional gene product. Del Bigio et al. (2011) postulated that a disruption of CRYAB interaction with titin (TTN; 188840) may contribute to reduced muscle elasticity. </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 CARDIOMYOPATHY, DILATED, 1II</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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CRYAB, ARG157HIS
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<br />
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SNP: rs141638421,
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gnomAD: rs141638421,
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ClinVar: RCV000034838, RCV002336111, RCV002490468
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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 71-year-old Japanese woman with mild, late-onset dilated cardiomyopathy (CMD1II; 615184), Inagaki et al. (2006) identified heterozygosity for a G-A transition in exon 3 of the CRYAB gene, resulting in an arg157-to-his (R157H) substitution at an evolutionarily conserved residue. The patient had 2 sibs with CMD and 2 other sibs who had sudden cardiac death, but DNA was not available for analysis from any family members. The mutation was not found in 400 control chromosomes. Functional analysis showed decreased binding of the R157H mutant to the heart-specific N2B domain of titin (TTN; 188840) compared to wildtype, without affecting distribution in cardiomyocytes. </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 CARDIOMYOPATHY, DILATED, 1II</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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CRYAB, GLY154SER
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<br />
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SNP: rs150516929,
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gnomAD: rs150516929,
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ClinVar: RCV000034839, RCV000037217, RCV000157153, RCV000203359, RCV000297606, RCV000352488, RCV000398508, RCV000620796, RCV000658624, RCV000852658, RCV001170406, RCV003914912
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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 48-year-old woman with mild, late-onset dilated cardiomyopathy (CMD1II; 615184), Pilotto et al. (2006) identified heterozygosity for a G-A transition in the CRYAB gene, resulting in a gly154-to-ser (G154S) substitution at an evolutionarily conserved residue. DNA was unavailable from her father, who died at age 80 after a 20-year history of congestive heart failure due to CMD; the mutation was not found in 200 controls. The patient had a minimal increase in serum CPK, suggestive of possible subclinical muscle involvement. </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>.0008 CATARACT 16, CONGENITAL LAMELLAR</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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CRYAB, ASP140ASN
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<br />
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SNP: rs387907336,
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|
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ClinVar: RCV000034840
|
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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 5-generation Chinese family with congenital lamellar cataract (CTRCT16; 613763), Liu et al. (2006) identified heterozygosity for a G-A transition in exon 3 of the CRYAB gene, resulting in an asp140-to-asn (D140N) substitution within the highly conserved alpha-crystallin domain. The mutation was not found in 5 unaffected members of the family or in 100 controls. In functional analyses, the mutant alpha-B crystallin showed abnormal oligomerization, reduced thermal stability, and abolished chaperone-like activity. In addition, the D140N mutant acted as a dominant negative, interfering with the chaperone-like activity of wildtype alpha-B crystallin. </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>.0009 CATARACT 16, POSTERIOR POLAR</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
CRYAB, PRO20SER
|
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|
<br />
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|
|
|
SNP: rs387907337,
|
|
|
|
|
|
|
|
ClinVar: RCV000034841
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 13 affected members of a 4-generation Chinese family with congenital posterior polar cataract (CTRCT16; 613763), Liu et al. (2006) identified heterozygosity for a 58C-T transition in exon 1 of the CRYAB gene, resulting in a pro20-to-ser (P20S) substitution at a highly conserved residue in the N-terminal region of alpha-B crystallin. The mutation was not found in 8 unaffected family members or in 200 controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CATARACT, JUVENILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRYAB, ARG56TRP
|
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|
|
|
<br />
|
|
|
|
SNP: rs387907338,
|
|
|
|
|
|
gnomAD: rs387907338,
|
|
|
|
|
|
ClinVar: RCV000034842, RCV001852700, RCV003984812, RCV004018734
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an affected mother and her 4 affected children from a consanguineous Saudi Arabian family with juvenile cataract (CTRCT16; 613763), Safieh et al. (2009) identified homozygosity for a 166C-T transition in exon 1 of the CRYAB gene, resulting in an arg56-to-trp (R56W) substitution at a highly conserved residue. The unaffected father was heterozygous for the mutation, which was not found in 150 Saudi controls. The 35-year-old mother also had retinal dystrophic changes; Safieh et al. (2009) noted that it was unclear whether the retinal phenotype was related to the CRYAB mutation or due to another cause. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MYOPATHY, MYOFIBRILLAR, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRYAB, ASP109HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907339,
|
|
|
|
|
|
gnomAD: rs387907339,
|
|
|
|
|
|
ClinVar: RCV000034843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all affected members of a family of North African origin with myofibrillar myopathy, posterior polar cataract, and dilated cardiomyopathy (608810), Sacconi et al. (2012) identified heterozygosity for a 325G-C transversion in exon 3 of the CRYAB gene, resulting in an asp109-to-his (D109H) substitution at a conserved residue involved in dimerization of the protein. The mutation was not found in unaffected family members or in 50 ethnically matched controls. Molecular modeling indicated that D109 interacts with R120 on the opposite alpha-B crystallin monomer during dimerization; Sacconi et al. (2012) noted that R120 was previously found to be mutated in a French family with a similar phenotype involving myofibrillar myopathy, cardiomyopathy, and cataract (R120G; 123590.0001). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
|
|
</div>
|
|
|
|
|
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|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Quax-Jeuken et al. (1985); Rappaport et al. (1988); Vicart et al.
|
|
(1996)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
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|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Berry, V., Francis, P., Reddy, M. A., Collyer, D., Vithana, E., MacKay, I., Dawson, G., Carey, A. H., Moore, A., Bhattacharya, S. S., Quinlan, R. A.
|
|
<strong>Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.</strong>
|
|
Am. J. Hum. Genet. 69: 1141-1145, 2001.
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|
|
|
|
|
[PubMed: 11577372]
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[Full Text: https://doi.org/10.1086/324158]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Brakenhoff, R. H., Geurts van Kessel, A. H. M., Oldenburg, M., Wijnen, J. T., Bloemendal, H., Meera Khan, P., Schoenmakers, J. G. G.
|
|
<strong>Human alpha-B-crystallin (CRYA2) gene mapped to chromosome 11q12-q23.</strong>
|
|
Hum. Genet. 85: 237-240, 1990.
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[PubMed: 2370055]
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[Full Text: https://doi.org/10.1007/BF00193203]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chavez Zobel, A. T., Loranger, A., Marceau, N., Theriault, J. R., Lambert, H., Landry, J.
|
|
<strong>Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alpha-B-crystallin mutant.</strong>
|
|
Hum. Molec. Genet. 12: 1609-1620, 2003.
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[PubMed: 12812987]
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[Full Text: https://doi.org/10.1093/hmg/ddg173]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Del Bigio, M. R., Chudley, A. E., Sarnat, H. B., Campbell, C., Goobie, S., Chodirker, B. N., Selcen, D.
|
|
<strong>Infantile muscular dystrophy in Canadian aboriginals is an alpha-B-crystallinopathy.</strong>
|
|
Ann. Neurol. 69: 866-871, 2011.
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[PubMed: 21337604]
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[Full Text: https://doi.org/10.1002/ana.22331]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Dubin, R. A., Ally, A. H., Chung, S., Piatigorsky, J.
|
|
<strong>Human alpha-B-crystallin gene and preferential promoter function in lens.</strong>
|
|
Genomics 7: 594-601, 1990.
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[PubMed: 2387586]
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[Full Text: https://doi.org/10.1016/0888-7543(90)90204-8]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Dubin, R. A., Wawrousek, E. F., Piatigorsky, J.
|
|
<strong>Expression of the murine alpha-B-crystallin gene is not restricted to the lens.</strong>
|
|
Molec. Cell Biol. 9: 1083-1091, 1989.
|
|
|
|
|
|
[PubMed: 2725488]
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|
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|
|
[Full Text: https://doi.org/10.1128/mcb.9.3.1083-1091.1989]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Fardeau, M., Godet-Guillain, J., Tome, F. M., Collin, H., Gardeau, S., Boffety, C., Vernant, P.
|
|
<strong>Une nouvelle affection musculaire familiale, definie par l'accumulation intra-sarco-plasmique d'un materiel granulo-filamenta ire dense en microscopie electronique.</strong>
|
|
Rev. Neurol. 134: 411-425, 1978.
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|
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|
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[PubMed: 570292]
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|
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fu, L., Liang, J. J.-N.
|
|
<strong>Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay.</strong>
|
|
J. Biol. Chem. 277: 4255-4260, 2002.
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[PubMed: 11700327]
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|
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Fu, L., Liang, J. J.-N.
|
|
<strong>Alteration of protein-protein interactions of congenital cataract crystallin mutants.</strong>
|
|
Invest. Ophthal. Vis. Sci. 44: 1155-1159, 2003.
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|
|
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|
[PubMed: 12601044]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Gupta, R., Srivastava, O. P.
|
|
<strong>Effect of deamidation of asparagine 146 on functional and structural properties of human lens alpha-B-crystallin.</strong>
|
|
Invest. Ophthal. Vis. Sci. 45: 206-214, 2004.
|
|
|
|
|
|
[PubMed: 14691175]
|
|
|
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|
|
[Full Text: https://doi.org/10.1167/iovs.03-0720]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Hagemann, T. L., Boelens, W. C., Wawrousek, E. F., Messing, A.
|
|
<strong>Suppression of GFAP toxicity by alpha-B-crystallin in mouse models of Alexander disease.</strong>
|
|
Hum. Molec. Genet. 18: 1190-1199, 2009.
|
|
|
|
|
|
[PubMed: 19129171]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddp013]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hayes, V. H., Devlin, G., Quinlan, R. A.
|
|
<strong>Truncation of alpha-beta-crystallin by the myopathy-causing Q151X mutation significantly destabilizes the protein leading to aggregate formation in transfected cells.</strong>
|
|
J. Biol. Chem. 283: 10500-10512, 2008.
|
|
|
|
|
|
[PubMed: 18230612]
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|
|
[Full Text: https://doi.org/10.1074/jbc.M706453200]
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</p>
|
|
</li>
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Elizabeth S. Partan - updated : 01/28/2021<br>Ada Hamosh - updated : 09/15/2016<br>Ada Hamosh - updated : 1/5/2015<br>Marla J. F. O'Neill - updated : 6/12/2013<br>Marla J. F. O'Neill - updated : 4/18/2013<br>Ada Hamosh - updated : 4/9/2012<br>Cassandra L. Kniffin - updated : 4/5/2011<br>George E. Tiller - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 5/22/2008<br>Ada Hamosh - updated : 8/20/2007<br>Patricia A. Hartz - updated : 3/28/2006<br>George E. Tiller - updated : 4/26/2005<br>Cassandra L. Kniffin - reorganized : 7/23/2004<br>Cassandra L. Kniffin - updated : 7/22/2004<br>Jane Kelly - updated : 6/14/2004<br>Jane Kelly - updated : 3/4/2004<br>Cassandra L. Kniffin - updated : 2/5/2004<br>Victor A. McKusick - updated : 11/27/2001<br>Victor A. McKusick - updated : 8/28/1998
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Victor A. McKusick : 6/4/1986
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carol : 02/21/2023<br>mgross : 01/28/2021<br>carol : 12/03/2020<br>alopez : 09/15/2016<br>carol : 06/23/2016<br>alopez : 1/5/2015<br>carol : 8/7/2013<br>carol : 6/12/2013<br>carol : 4/18/2013<br>carol : 8/28/2012<br>alopez : 4/9/2012<br>terry : 4/9/2012<br>terry : 6/23/2011<br>wwang : 4/22/2011<br>wwang : 4/12/2011<br>ckniffin : 4/7/2011<br>wwang : 4/7/2011<br>ckniffin : 4/5/2011<br>carol : 2/22/2011<br>wwang : 11/10/2009<br>terry : 10/27/2009<br>wwang : 1/9/2009<br>wwang : 5/23/2008<br>ckniffin : 5/22/2008<br>alopez : 8/31/2007<br>terry : 8/20/2007<br>carol : 12/15/2006<br>carol : 11/30/2006<br>wwang : 4/4/2006<br>terry : 3/28/2006<br>tkritzer : 4/26/2005<br>carol : 7/23/2004<br>ckniffin : 7/22/2004<br>alopez : 6/14/2004<br>mgross : 3/17/2004<br>alopez : 3/5/2004<br>alopez : 3/5/2004<br>alopez : 3/4/2004<br>tkritzer : 2/12/2004<br>ckniffin : 2/5/2004<br>alopez : 12/3/2001<br>terry : 11/27/2001<br>dkim : 9/10/1998<br>alopez : 8/31/1998<br>terry : 8/28/1998<br>terry : 8/24/1998<br>alopez : 4/13/1998<br>terry : 12/5/1996<br>terry : 7/10/1995<br>mark : 6/28/1995<br>carol : 2/25/1993<br>supermim : 3/16/1992<br>carol : 9/14/1990<br>carol : 8/23/1990
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