3585 lines
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Entry
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- *607444 - SBDS RIBOSOME MATURATION FACTOR; SBDS
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*607444</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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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="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607444">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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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=ENSG00000126524;t=ENST00000246868" 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=51119" 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=607444" 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=ENSG00000126524;t=ENST00000246868" 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_016038" 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_016038" 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=607444" 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=07393&isoform_id=07393_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/SBDS" 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/4929663,7023264,27802129,28380824,28416940,41350825,45722535,119628311,158260241,957951096,957951099" 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/Q9Y3A5" 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=51119" 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=ENSG00000126524;t=ENST00000246868" 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=SBDS" 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=SBDS" 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+51119" 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/SBDS" 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:51119" 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/51119" 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=chr7&hgg_gene=ENST00000246868.7&hgg_start=66987680&hgg_end=66995586&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:19440" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:19440" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/sbds" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607444[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=607444[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SBDS/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000126524" 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=SBDS" 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=SBDS" 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=SBDS" 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://structure.bmc.lu.se/idbase/SBDSbase/" 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=SBDS&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/PA134978742" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:19440" 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/FBgn0035714.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:1913961" 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/SBDS#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:1913961" 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/51119/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=51119" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00021063;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1116" 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:51119" 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=SBDS&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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</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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607444
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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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SBDS RIBOSOME MATURATION FACTOR; SBDS
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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>
|
|
<span class="mim-font">
|
|
SBDS GENE
|
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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=SBDS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SBDS</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/7/303?start=-3&limit=10&highlight=303">7q11.21</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:66987680-66995586&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'})">7:66,987,680-66,995,586</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=609135,260400" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/303?start=-3&limit=10&highlight=303">
|
|
7q11.21
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
{Aplastic anemia, susceptibility to}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/609135"> 609135 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Shwachman-Diamond syndrome 1
|
|
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/260400"> 260400 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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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<p><a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> screened 18 positional candidate genes in the critical region on chromosome 7q11 identified by linkage analysis for Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>), an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, hematologic dysfunction, and skeletal abnormalities. They discovered mutations associated with Shwachman-Diamond syndrome in an uncharacterized gene represented by the 1.6-kb cDNA clone FLJ10917 (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AK001779" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AK001779</a>). They designated the gene SBDS for 'Shwachman-Bodian-Diamond syndrome.' SBDS is a member of a highly conserved protein family, with orthologs in species ranging from archaea to vertebrates and plants. Indirect lines of evidence suggested that the orthologs may function in RNA metabolism. The predicted protein is 28.8 kD with a pI of 8.9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> determined that the SBDS gene contains of 5 exons spanning 7.9 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> mapped the SBDS gene to chromosome 7q11. SBDS and an adjacent gene reside in a block of 305 kb that is locally duplicated. The paralogous duplicon is located 5.8 Mb distally and contains an unprocessed pseudogene copy of SBDS designated SBDSP. The pseudogene transcript is 97% identical to SBDS and contains deletions and nucleotide changes that disrupt coding potential. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#2" class="mim-tip-reference" title="Austin, K. M., Leary, R. J., Shimamura, A. <strong>The Shwachman-Diamond SBDS protein localizes to the nucleolus.</strong> Blood 106: 1253-1258, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15860664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15860664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15860664[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2005-02-0807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15860664">Austin et al. (2005)</a> found that SBDS protein was present in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell cycle-dependent, with nucleolar localization during G1 and G2 and diffuse nuclear localization during S phase. The intranucleolar localization of SBDS provided further supportive evidence for its postulated role in the processing of ribosomal RNA (rRNA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15860664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ganapathi, K. A., Austin, K. M., Lee, C.-S., Dias, A., Malsch, M. M., Reed, R., Shimamura, A. <strong>The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA.</strong> Blood 110: 1458-1465, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17475909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17475909</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17475909[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2007-02-075184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17475909">Ganapathi et al. (2007)</a> presented in vitro evidence indicating that the SBDS gene is involved with ribosomal RNA. Nucleolar localization of SBDS was dependent on active ribosomal RNA transcription. Lymphoblast cell lines derived from SDS patients showed hypersensitivity to actinomycin D, which inhibits RNA polymerase I, indicating an underlying impairment of ribosome biogenesis. SBDS migrated with the 60S ribosomal precursor protein, and associated with the 28S subunit (see <a href="/entry/180450">180450</a>) and nucleophosmin (see <a href="/entry/164040">164040</a>). SBDS knockdown markedly decreased production of newly synthesized rRNA, although an imbalance of ribosomal subunits could not be detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17475909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#11" class="mim-tip-reference" title="Menne, T. F., Goyenechea, B., Sanchez-Puig, N., Wong, C. C., Tonkin, L. M., Ancliff, P. J., Brost, R. L., Costanzo, M., Boone, C., Warren, A. J. <strong>The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.</strong> Nature Genet. 39: 486-495, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17353896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17353896</a>] [<a href="https://doi.org/10.1038/ng1994" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17353896">Menne et al. (2007)</a> identified the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, they identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1-delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. The data of <a href="#11" class="mim-tip-reference" title="Menne, T. F., Goyenechea, B., Sanchez-Puig, N., Wong, C. C., Tonkin, L. M., Ancliff, P. J., Brost, R. L., Costanzo, M., Boone, C., Warren, A. J. <strong>The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.</strong> Nature Genet. 39: 486-495, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17353896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17353896</a>] [<a href="https://doi.org/10.1038/ng1994" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17353896">Menne et al. (2007)</a> linked defective 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17353896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Austin, K. M., Gupta, M. L., Jr., Coats, S. A., Tulpule, A., Mostoslavsky, G., Balazs, A. B., Mulligan, R. C., Daley, G., Pellman, D., Shimamura, A. <strong>Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome.</strong> J. Clin. Invest. 118: 1511-1518, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18324336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18324336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18324336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI33764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18324336">Austin et al. (2008)</a> found that SBDS colocalized with mitotic spindles and bound to purified microtubules, thus preventing genomic instability, in wildtype human bone marrow stromal cells, lymphoblasts, and skin fibroblasts. Primary bone marrow stromal cells and lymphoblasts from SDS patients exhibited an increased incidence of abnormal mitoses. Depletion of the SBDS gene using siRNA in normal skin fibroblasts resulted in increased mitotic abnormalities and aneuploidy that accumulated over time. Treatment of primary cells from SDS patients with nocodazole, a microtubule destabilizing agent, led to increased mitotic arrest and apoptosis compared to treated wildtype cells. In addition, SDS patient cells were resistant to taxol, a microtubule stabilizing agent. These findings suggested that spindle instability in SDS contributes to bone marrow failure and leukemogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18324336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Vitiello, S. P., Benedict, J. W., Padilla-Lopez, S., Pearce, D. A. <strong>Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model for Batten disease.</strong> Hum. Molec. Genet. 19: 931-942, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20015955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20015955">Vitiello et al. (2010)</a> demonstrated that CLN3 (<a href="/entry/607042">607042</a>) interacts with SBDS. The protein-protein interaction was conserved between Btn1 and Sdo1, the respective S. cerevisiae orthologs of CLN3 and SBDS. It had been shown that deletion of Btn1 resulted in alterations in vacuolar pH and vacuolar (H+)-ATPase (V-ATPase)-dependent H+ transport and ATP hydrolysis. <a href="#16" class="mim-tip-reference" title="Vitiello, S. P., Benedict, J. W., Padilla-Lopez, S., Pearce, D. A. <strong>Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model for Batten disease.</strong> Hum. Molec. Genet. 19: 931-942, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20015955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20015955">Vitiello et al. (2010)</a> found that an Sdo1 deletion strain had decreased vacuolar pH and V-ATPase-dependent H+ transport and ATP hydrolysis; the alterations resulted from decreased V-ATPase subunit expression. Overexpression of Btn1 or the presence of ionophore carbonyl cyanide chlorophenil hydrazone (CCCP) caused decreased growth in yeast lacking Sdo1. In normal cells, overexpression of Btn1 mirrored the effect of CCCP, with both resulting in increased vacuolar pH due to alterations in the coupling of V-ATPase-dependent H+ transport and ATP hydrolysis. <a href="#16" class="mim-tip-reference" title="Vitiello, S. P., Benedict, J. W., Padilla-Lopez, S., Pearce, D. A. <strong>Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model for Batten disease.</strong> Hum. Molec. Genet. 19: 931-942, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20015955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20015955">Vitiello et al. (2010)</a> proposed that Sdo1 and SBDS work to regulate Btn1 and CLN3, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20015955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> demonstrated that deletion of Dicer1 (<a href="/entry/606241">606241</a>) specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of hematopoiesis. Myelodysplasia resulted and acute myelogenous leukemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Shwachman-Bodian-Diamond syndrome, a human bone marrow failure and leukemia predisposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, <a href="#13" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> concluded that perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation, and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, <a href="#13" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> concluded that primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20305640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 affinity capture and mass spectrometry, <a href="#3" class="mim-tip-reference" title="Ball, H. L., Zhang, B., Riches, J. J., Gandhi, R., Li, J., Rommens, J. M., Myers, J. S. <strong>Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses.</strong> Hum. Molec. Genet. 18: 3684-3695, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19602484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19602484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19602484[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19602484">Ball et al. (2009)</a> developed an SBDS interactome and reported SBDS binding partners with diverse molecular functions, notably components of the large ribosomal subunit and proteins involved in DNA metabolism. Reciprocal coimmunoprecipitation confirmed the interaction of SBDS with the large ribosomal subunit protein RPL4 (<a href="/entry/180479">180479</a>) and with DNA-PK (PRKDC; <a href="/entry/600899">600899</a>) and RPA70 (RPA1; <a href="/entry/179835">179835</a>), 2 proteins with critical roles in DNA repair. SBDS-depleted HEK293 cells were hypersensitive to multiple types of DNA damage as well as chemically induced endoplasmic reticulum stress, suggesting a role for SBDS in response to cellular stress. SBDS-dependent hypersensitivity of HEK293 cells to UV irradiation could be distinguished from a role of SBDS in translation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19602484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#6" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> showed that GTP and recombinant human SBDS and elongation factor-like-1 (EFL1, or EFTUD1) cooperated to trigger release of human EIF6 (<a href="/entry/602912">602912</a>) from pre60S ribosomes isolated from Sbds-deficient mouse livers. EFL1 and SBDS independently and noncooperatively bound to the 60S subunit in vitro. The 60S subunit activated the GTPase activity of EFL1, but SBDS was required to stimulate EIF6 release. Two SBDS mutants with different SDS-associated missense mutations varied in their ability to enhance 60S-dependent GTPase activity of EFL1, but neither triggered EIF6 release. <a href="#6" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> concluded that SBDS and EFL1 catalyze translational activation and proposed that SDS is a ribosomopathy caused by uncoupling GTP hydrolysis from EIF6 release. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21536732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N. <strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong> J. Biol. Chem. 290: 17669-17678, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M114.626275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25991726">Garcia-Marquez et al. (2015)</a> determined that the affinity of EFL1 for GTP was 10-fold lower than that calculated for GDP. Association of EFL1 with SBDS did not alter the affinity of EFL1 for GTP, but significantly reduced its dissociation constant for GDP. Thus, SBDS acted as a guanine nucleotide exchange factor (GEF) for EFL1, promoting activation of EFL1 by release of GDP. <a href="#8" class="mim-tip-reference" title="Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N. <strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong> J. Biol. Chem. 290: 17669-17678, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M114.626275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25991726">Garcia-Marquez et al. (2015)</a> concluded that SBDS couples the energy liberated from the hydrolysis of GTP by EFL1 for release of EIF6 from the surface of the 60S ribosomal subunit. They further found that SBDS mutations found in patients with Shwachman-Diamond syndrome disrupted the interaction of SBDS with EFL1 and prevented SBDS regulation of the affinity of EFL1 toward guanine nucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25991726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Independently, <a href="#14" class="mim-tip-reference" title="Savchenko, A., Krogan, N., Cort, J. R., Evdokimova, E., Lew, J. M., Yee, A. A., Sanchez-Pulido, L., Andrade, M. A., Bochkarev, A., Watson, J. D., Kennedy, M. A., Greenblatt, J., Hughes, T., Arrowsmith, C. H., Rommens, J. M., Edwards, A. M. <strong>The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism.</strong> J. Biol. Chem. 280: 19213-19220, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15701634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15701634</a>] [<a href="https://doi.org/10.1074/jbc.M414421200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15701634">Savchenko et al. (2005)</a> and <a href="#15" class="mim-tip-reference" title="Shammas, C., Menne, T. F., Hilcenko, C., Michell, S. R., Goyenechea, B., Boocock, G. R. B., Durie, P. R., Rommens, J. M., Warren, A. J. <strong>Structural and mutational analysis of the SBDS protein family: insight into the leukemia-associated Shwachman-Diamond syndrome.</strong> J. Biol. Chem. 280: 19221-19229, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15701631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15701631</a>] [<a href="https://doi.org/10.1074/jbc.M414656200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15701631">Shammas et al. (2005)</a> determined the crystal structure of the Archaeglobus fulgidus ortholog of SBDS. They found that A. fulgidus Sbds assumes a highly conserved 3-domain structure consisting of an N-terminal domain with a novel 3-dimensional fold structure, a central domain containing a winged helix-turn-helix motif, and a C-terminal domain that shares structural homology with RNA-binding proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15701631+15701634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> reported mutations in the SBDS gene in affected individuals from 158 families with Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>). Gene conversion mutations accounted for 74.4% of alleles associated with Shwachman-Diamond syndrome (235 of 316). Observations indicated that gene conversion due to recombination between SBDS and its pseudogene had occurred. Conversion mutations were found in 89% of individuals with Shwachman-Diamond syndrome (141 of 158). <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> suggested that the conversion events are confined to a short segment spanning approximately 240 bp in exon 2. In 79 of 141 families with Shwachman-Diamond syndrome with conversion mutations, Boocock et al. (2003) found that affected individuals were compound heterozygous for 2 mutations in exon 2 of the SBDS gene: 183-184TA-CT (<a href="#0001">607444.0001</a>) and 258+2T-C (IVS2DS+2T-C; 607444.0002). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 study of Japanese patients with SDS, <a href="#12" class="mim-tip-reference" title="Nakashima, E., Mabuchi, A., Makita, Y., Masuno, M., Ohashi, H., Nishimura, G., Ikegawa, S. <strong>Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.</strong> Hum. Genet. 114: 345-348, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749921</a>] [<a href="https://doi.org/10.1007/s00439-004-1081-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14749921">Nakashima et al. (2004)</a> likewise found mutations in the SBDS gene caused by gene conversion. The sites of the gene conversion events varied, extending from intron 1 to exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14749921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Abnormalities in chromosome 7 have been reported in association with Shwachman-Diamond syndrome, especially an isochromosome i(7)(q10). In a 25-year-old patient with SDS who suffered from mild aplastic anemia but showed no signs of either myelodysplasia or leukemic transformation, <a href="#10" class="mim-tip-reference" title="Mellink, C. H. M., Alders, M., van der Lelie, H., Hennekam, R. H. C., Kuijpers, T. W. <strong>SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation?</strong> Cancer Genet. Cytogenet. 154: 144-149, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15474150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15474150</a>] [<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15474150">Mellink et al. (2004)</a> identified an isochromosome i(7)(q10) in the bone marrow and also identified 2 different mutations in the SBDS gene: the 183-184TA-CT mutation was present in 1 allele and the splice site mutation 258+2T-C was present in the other. The 2 mutations were the most commonly found in the study of <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a>. <a href="#10" class="mim-tip-reference" title="Mellink, C. H. M., Alders, M., van der Lelie, H., Hennekam, R. H. C., Kuijpers, T. W. <strong>SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation?</strong> Cancer Genet. Cytogenet. 154: 144-149, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15474150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15474150</a>] [<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15474150">Mellink et al. (2004)</a> concluded that the isochromosome 7q phenomenon may have a very indirect association with the pathogenesis of malignant transformation in SDS patients. It may be the first presentation of chromosome instability that could eventually result in more significant additional chromosomal aberrations involved in the clinical manifestation of acute myeloid leukemia and myelodysplasia syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15474150+12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Austin, K. M., Leary, R. J., Shimamura, A. <strong>The Shwachman-Diamond SBDS protein localizes to the nucleolus.</strong> Blood 106: 1253-1258, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15860664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15860664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15860664[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2005-02-0807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15860664">Austin et al. (2005)</a> characterized the SBDS protein expression and intracellular localization in 7 patients with Shwachman-Diamond syndrome and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. One patient, who was homozygous for the IVS2DS+2T-C mutation (<a href="#0002">607444.0002</a>), expressed scant levels of SBDS protein. A second patient, harboring a missense mutation, expressed low levels of SBDS protein. A third patient, who carried no detectable gene mutations, expressed wildtype levels of SBDS protein, adding further support to the growing body of evidence for additional genes that might contribute to the pathogenesis of the disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15860664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Sanger sequencing in 2 patients with SDS, <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> identified compound heterozygous mutations in the SBDS gene: c.258+2T-C on one allele and c.183-184TA-CT and c.201A-G on the other allele. However, the c.183-184TA-CT and c.201A-G variants were not identified by whole-exome sequencing in either patient. <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> concluded that these variants were missed by whole-exome analysis due to mismapping of reads resulting from the inability to discriminate between SBDS and the SBDSP1 pseudogene. All 3 variants were identified with transcriptome analysis via RNAseq in blood samples from both patients, leading <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> to conclude that RNA-seq is an effective assay for the diagnosis of SDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32412173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Aplastic Anemia, Susceptibility to</em></strong></p><p>
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<a href="#5" class="mim-tip-reference" title="Calado, R. T., Graf, S. A., Wilkerson, K. L., Kajigaya, S., Ancliff, P. J., Dror, Y., Chanock, S. J., Lansdorp, P. M., Young, N. S. <strong>Mutations in the SBDS gene in acquired aplastic anemia.</strong> Blood 110: 1141-1146, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17478638[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2007-03-080044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478638">Calado et al. (2007)</a> identified heterozygosity for the IVS2DS+2T-C mutation (<a href="#0002">607444.0002</a>) in the SBDS gene in 4 of 91 unrelated patients with aplastic anemia (<a href="/entry/609135">609135</a>). These patients were younger on average (5 to 19 years) compared to other patients with aplastic anemia. Two mothers tested were carriers of the mutation; these 2 and another mother who was not tested had histories of subclinical mild anemia. Heterozygous mutation carriers had partial loss of SBDS protein expression, indicating haploinsufficiency. Although telomere shortening was observed in patients' granulocytes, lymphocytes had normal telomere length. None of the patients with aplastic anemia had pancreatic exocrine failure or skeletal anomalies as seen in SDS. One of the 4 probands was also heterozygous for a presumed pathogenic variant in the TERT gene (<a href="/entry/187270">187270</a>). The outcome of these patients was poor, with 2 deaths. <a href="#5" class="mim-tip-reference" title="Calado, R. T., Graf, S. A., Wilkerson, K. L., Kajigaya, S., Ancliff, P. J., Dror, Y., Chanock, S. J., Lansdorp, P. M., Young, N. S. <strong>Mutations in the SBDS gene in acquired aplastic anemia.</strong> Blood 110: 1141-1146, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17478638[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2007-03-080044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478638">Calado et al. (2007)</a> concluded that SBDS deficiency predisposes to marrow failure by causing telomere shortening, thus indicating a role for SBDS in the maintenance of telomere length. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M. <strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong> Blood 106: 356-361, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15769891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15769891</a>] [<a href="https://doi.org/10.1182/blood-2004-11-4371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15769891">Kuijpers et al. (2005)</a> sequenced the SBDS gene in 20 unrelated patients with clinical SDS and identified mutations in 15 (75%), with identical compound heterozygosity in 11 patients (see <a href="#0001">607444.0001</a> and <a href="#0002">607444.0002</a>). The authors examined hematologic parameters over 5 years of follow-up and observed persistent neutropenia in 43% in the absence of apoptosis and unrelated to chemotaxis defects or infection rate. Irrespective of the absolute neutrophil count in vivo, abnormal granulocyte-monocyte colony formation was observed in all patients with SDS tested (14 of 14), whereas erythroid and myeloid colony formation was less often affected (9 of 14). Cytogenetic aberrations occurred in 5 of 19 patients in the absence of myelodysplasia. <a href="#9" class="mim-tip-reference" title="Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M. <strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong> Blood 106: 356-361, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15769891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15769891</a>] [<a href="https://doi.org/10.1182/blood-2004-11-4371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15769891">Kuijpers et al. (2005)</a> concluded that in patients with genetically proven SDS, a genotype/phenotype relationship does not exist in clinical and hematologic terms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15769891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#18" class="mim-tip-reference" title="Zhang, S., Shi, M., Hui, C., Rommens, J. M. <strong>Loss of the mouse ortholog of the Shwachman-Diamond syndrome gene (Sbds) results in early embryonic lethality.</strong> Molec. Cell Biol. 26: 6656-6663, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16914746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16914746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16914746[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.00091-06" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16914746">Zhang et al. (2006)</a> reported that loss of the Sbds gene resulted in early lethality in mice prior to embryonic day 6.5. Heterozygous mutant mice had a normal phenotype and were indistinguishable from wildtype littermates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16914746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#6" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> also found that Sbds deletion in mice was embryonic lethal. Sbds -/- mice showed prominent histologic abnormalities in liver, with disordered architecture between the portal triads and central veins, degenerative hepatocyte appearance, and scattered subcapsular areas of hepatocyte necrosis with an associated acute inflammatory reaction. Sbds-deleted liver extracts showed accumulation of free cytoplasmic 40S and 60S subunits and 43S initiation complexes that were stalled at the AUG start codon awaiting binding of 60S subunits, suggesting a ribosomal subunit-joining defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21536732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs113993991 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113993991;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=rs113993991" 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=rs113993991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs120074160 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs120074160;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/rs120074160?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=rs120074160" 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=rs120074160" 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=RCV000003346 OR RCV000255938 OR RCV000622680 OR RCV002496241 OR RCV003472961 OR RCV003904800 OR RCV004017224" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003346, RCV000255938, RCV000622680, RCV002496241, RCV003472961, RCV003904800, RCV004017224" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003346...</a>
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<p>In 79 of 141 families with Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>) with conversion mutations, <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> found that affected individuals were compound heterozygous for 2 mutations in exon 2 of the SBDS gene: 183-184TA-CT and 258+2T-C (IVS2DS+2T-C; <a href="#0002">607444.0002</a>). The dinucleotide alteration 183-184TA-CT introduced an in-frame stop codon (lys62 to ter; K62X). The 258+2T-C mutation was predicted to disrupt the donor splice site of intron 2; it resulted in an 8-bp deletion consistent with use of an upstream cryptic splice donor site at position 251-252. The 258+2T-C and the resultant 8-bp deletion caused premature termination of the encoded protein by frameshift. In 44 families there was compound heterozygosity of 258+2T-C with another allele. In 7 families there was homozygosity for 258+2T-C. No incidence of homozygosity for 183-184TA-CT was observed. In 8 alleles of the SBDS gene found by <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> in patients with SDS, both the 183-184TA-CT and the 258+2T-C change were on the same allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 11 patients with SDS, <a href="#9" class="mim-tip-reference" title="Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M. <strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong> Blood 106: 356-361, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15769891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15769891</a>] [<a href="https://doi.org/10.1182/blood-2004-11-4371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15769891">Kuijpers et al. (2005)</a> identified compound heterozygosity for the K62X and 258+2T-C mutations in the SBDS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15769891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Sanger sequencing in 2 patients with SDS, <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> identified compound heterozygous mutations in the SBDS gene: c.183-184TA-CT and c.201A-G on one allele and c.258+2T-C the other allele. However, the c.183-184TA-CT and c.201A-G variants were not identified by whole-exome sequencing in either patient. <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> concluded that these variants were missed by whole-exome analysis due to mismapping of reads resulting from the inability to discriminate between SBDS and the SBDSP1 pseudogene. All 3 variants were identified with transcriptome analysis via RNAseq in blood samples from both patients, leading <a href="#17" class="mim-tip-reference" title="Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K. <strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong> Am. J. Med. Genet. 182A: 1631-1636, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>] [<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32412173">Yamada et al. (2020)</a> to conclude that RNA-seq is an effective assay for the diagnosis of SDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32412173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 SHWACHMAN-DIAMOND SYNDROME 1</strong>
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APLASTIC ANEMIA, SUSCEPTIBILITY TO, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs113993993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113993993;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/rs113993993?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=rs113993993" 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=rs113993993" 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=RCV000003347 OR RCV000003348 OR RCV000255013 OR RCV000506317 OR RCV000623539 OR RCV000626935 OR RCV000763594 OR RCV001270036 OR RCV002272008 OR RCV003407264" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003347, RCV000003348, RCV000255013, RCV000506317, RCV000623539, RCV000626935, RCV000763594, RCV001270036, RCV002272008, RCV003407264" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003347...</a>
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<p><strong><em>Shwachman-Diamond Syndrome 1</em></strong></p><p>
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For discussion of the splice site mutation in the SBDS gene (IVS2DS+2T-C) that was found in compound heterozygous state in patients with Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>) by <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> and <a href="#9" class="mim-tip-reference" title="Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M. <strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong> Blood 106: 356-361, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15769891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15769891</a>] [<a href="https://doi.org/10.1182/blood-2004-11-4371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15769891">Kuijpers et al. (2005)</a>, see <a href="#0001">607444.0001</a>. <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> referred to this mutation as 258+2T-C. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12496757+15769891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Nakashima, E., Mabuchi, A., Makita, Y., Masuno, M., Ohashi, H., Nishimura, G., Ikegawa, S. <strong>Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.</strong> Hum. Genet. 114: 345-348, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749921</a>] [<a href="https://doi.org/10.1007/s00439-004-1081-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14749921">Nakashima et al. (2004)</a> identified this mutation in affected members of 4 Japanese families with SDS, making it the most prevalent mutation. Recurrent gene conversion was considered the most likely explanation for the recurrence, rather than founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14749921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Aplastic Anemia, Susceptibility to</em></strong></p><p>
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<a href="#5" class="mim-tip-reference" title="Calado, R. T., Graf, S. A., Wilkerson, K. L., Kajigaya, S., Ancliff, P. J., Dror, Y., Chanock, S. J., Lansdorp, P. M., Young, N. S. <strong>Mutations in the SBDS gene in acquired aplastic anemia.</strong> Blood 110: 1141-1146, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17478638[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2007-03-080044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478638">Calado et al. (2007)</a> identified heterozygosity for the IVS2DS+2T-C mutation in 4 of 91 unrelated patients with aplastic anemia (<a href="/entry/609135">609135</a>). These patients were younger on average (5 to 19 years) compared to other patients with aplastic anemia. Two mothers tested were carriers of the mutation; these 2 and another mother who was not tested had histories of subclinical mild anemia. Heterozygous mutation carriers had partial loss of SBDS protein expression, indicating haploinsufficiency. Although telomere shortening was observed in patients' granulocytes, lymphocytes had normal telomere length. None of the patients with aplastic anemia had pancreatic exocrine failure or skeletal anomalies as seen in SDS. One of the 4 probands was also heterozygous for a presumed pathogenic variant in the TERT gene (<a href="/entry/187270">187270</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SHWACHMAN-DIAMOND SYNDROME 1</strong>
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<p>In 1 allele from individuals with Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>), <a href="#4" class="mim-tip-reference" title="Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M. <strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong> Nature Genet. 33: 97-101, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>] [<a href="https://doi.org/10.1038/ng1062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496757">Boocock et al. (2003)</a> found a 24C-A transversion in the SBDS gene, predicted to result in an asn8-to-lys (N8K) amino acid change. The mutation on the other allele was not identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 affected members of 4 Japanese families with Shwachman-Diamond syndrome (SDS1; <a href="/entry/260400">260400</a>), <a href="#12" class="mim-tip-reference" title="Nakashima, E., Mabuchi, A., Makita, Y., Masuno, M., Ohashi, H., Nishimura, G., Ikegawa, S. <strong>Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.</strong> Hum. Genet. 114: 345-348, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749921</a>] [<a href="https://doi.org/10.1007/s00439-004-1081-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14749921">Nakashima et al. (2004)</a> found compound heterozygosity for 2 recurrent mutations in the SBDS gene: IVS2DS+2T-C (<a href="#0002">607444.0002</a>) and a 1-bp insertion (96insA) in exon 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14749921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>REFERENCES</strong>
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Austin, K. M., Leary, R. J., Shimamura, A.
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<strong>The Shwachman-Diamond SBDS protein localizes to the nucleolus.</strong>
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[<a href="https://doi.org/10.1182/blood-2005-02-0807" target="_blank">Full Text</a>]
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<a id="Ball2009" class="mim-anchor"></a>
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<p class="mim-text-font">
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Ball, H. L., Zhang, B., Riches, J. J., Gandhi, R., Li, J., Rommens, J. M., Myers, J. S.
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<strong>Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19602484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19602484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19602484[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19602484" 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/ddp316" target="_blank">Full Text</a>]
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<a id="Boocock2003" class="mim-anchor"></a>
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Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis, L., Durie, P. R., Rommens, J. M.
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<strong>Mutations in SBDS are associated with Shwachman-Diamond syndrome.</strong>
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Nature Genet. 33: 97-101, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496757" 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/ng1062" target="_blank">Full Text</a>]
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Calado, R. T., Graf, S. A., Wilkerson, K. L., Kajigaya, S., Ancliff, P. J., Dror, Y., Chanock, S. J., Lansdorp, P. M., Young, N. S.
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<strong>Mutations in the SBDS gene in acquired aplastic anemia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17478638[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478638" 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/10.1182/blood-2007-03-080044" target="_blank">Full Text</a>]
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Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J.
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<strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21536732" 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/10.1101/gad.623011" target="_blank">Full Text</a>]
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Ganapathi, K. A., Austin, K. M., Lee, C.-S., Dias, A., Malsch, M. M., Reed, R., Shimamura, A.
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<strong>The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17475909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17475909</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17475909[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17475909" 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/10.1182/blood-2007-02-075184" target="_blank">Full Text</a>]
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Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25991726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M114.626275" target="_blank">Full Text</a>]
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<a id="Kuijpers2005" class="mim-anchor"></a>
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Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M.
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<strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong>
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[<a href="https://doi.org/10.1182/blood-2004-11-4371" target="_blank">Full Text</a>]
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<a id="Mellink2004" class="mim-anchor"></a>
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Mellink, C. H. M., Alders, M., van der Lelie, H., Hennekam, R. H. C., Kuijpers, T. W.
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<strong>SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation?</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15474150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15474150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15474150" 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.cancergencyto.2004.02.001" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Menne2007" class="mim-anchor"></a>
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<div class="">
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Menne, T. F., Goyenechea, B., Sanchez-Puig, N., Wong, C. C., Tonkin, L. M., Ancliff, P. J., Brost, R. L., Costanzo, M., Boone, C., Warren, A. J.
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<strong>The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.</strong>
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Nature Genet. 39: 486-495, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17353896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17353896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17353896" 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/ng1994" target="_blank">Full Text</a>]
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<a id="Nakashima2004" class="mim-anchor"></a>
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<div class="">
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Nakashima, E., Mabuchi, A., Makita, Y., Masuno, M., Ohashi, H., Nishimura, G., Ikegawa, S.
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<strong>Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.</strong>
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Hum. Genet. 114: 345-348, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14749921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14749921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14749921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-004-1081-2" target="_blank">Full Text</a>]
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<div class="">
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Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T.
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<strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20305640" 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/nature08851" target="_blank">Full Text</a>]
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<a id="Savchenko2005" class="mim-anchor"></a>
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<strong>The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism.</strong>
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J. Biol. Chem. 280: 19213-19220, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15701634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15701634</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15701634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M414421200" target="_blank">Full Text</a>]
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</p>
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<a id="15" class="mim-anchor"></a>
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<a id="Shammas2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shammas, C., Menne, T. F., Hilcenko, C., Michell, S. R., Goyenechea, B., Boocock, G. R. B., Durie, P. R., Rommens, J. M., Warren, A. J.
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<strong>Structural and mutational analysis of the SBDS protein family: insight into the leukemia-associated Shwachman-Diamond syndrome.</strong>
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J. Biol. Chem. 280: 19221-19229, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15701631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15701631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15701631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M414656200" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Vitiello2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vitiello, S. P., Benedict, J. W., Padilla-Lopez, S., Pearce, D. A.
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<strong>Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model for Batten disease.</strong>
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Hum. Molec. Genet. 19: 931-942, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20015955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20015955" 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/ddp560" target="_blank">Full Text</a>]
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Yamada2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K.
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<strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong>
|
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Am. J. Med. Genet. 182A: 1631-1636, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32412173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32412173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32412173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61598" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Zhang2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, S., Shi, M., Hui, C., Rommens, J. M.
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<strong>Loss of the mouse ortholog of the Shwachman-Diamond syndrome gene (Sbds) results in early embryonic lethality.</strong>
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Molec. Cell Biol. 26: 6656-6663, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16914746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16914746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16914746[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16914746" 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/10.1128/MCB.00091-06" target="_blank">Full Text</a>]
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</p>
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</ol>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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">
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Hilary J. Vernon - updated : 03/19/2021
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 06/19/2017<br>George E. Tiller - updated : 11/8/2011<br>Patricia A. Hartz - updated : 5/16/2011<br>George E. Tiller - updated : 7/8/2010<br>Ada Hamosh - updated : 5/26/2010<br>Cassandra L. Kniffin - updated : 7/14/2008<br>Cassandra L. Kniffin - updated : 2/25/2008<br>Victor A. McKusick - updated : 4/26/2007<br>Marla J. F. O'Neill - updated : 12/12/2005<br>Victor A. McKusick - updated : 12/5/2005<br>Victor A. McKusick - updated : 1/31/2005<br>Victor A. McKusick - updated : 4/2/2004
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<a id="creationDate" class="mim-anchor"></a>
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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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<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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Victor A. McKusick : 12/23/2002
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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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">
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carol : 03/29/2021
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<span class="mim-text-font">
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carol : 03/19/2021<br>carol : 03/09/2021<br>carol : 06/19/2017<br>carol : 06/21/2016<br>mcolton : 7/13/2015<br>carol : 9/19/2013<br>alopez : 11/15/2011<br>terry : 11/8/2011<br>mgross : 6/10/2011<br>mgross : 6/10/2011<br>terry : 5/16/2011<br>wwang : 7/22/2010<br>terry : 7/8/2010<br>alopez : 5/27/2010<br>terry : 5/26/2010<br>wwang : 7/16/2008<br>ckniffin : 7/14/2008<br>terry : 6/6/2008<br>wwang : 3/5/2008<br>ckniffin : 2/25/2008<br>alopez : 4/30/2007<br>terry : 4/26/2007<br>carol : 1/30/2007<br>wwang : 12/12/2005<br>alopez : 12/7/2005<br>terry : 12/5/2005<br>tkritzer : 2/4/2005<br>terry : 1/31/2005<br>tkritzer : 12/13/2004<br>carol : 8/11/2004<br>tkritzer : 4/7/2004<br>terry : 4/2/2004<br>joanna : 2/26/2004<br>alopez : 12/23/2002
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</span>
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<span class="mim-font">
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<strong>*</strong> 607444
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<h3>
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<span class="mim-font">
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SBDS RIBOSOME MATURATION FACTOR; SBDS
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</span>
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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SBDS GENE
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SBDS</em></strong>
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<strong>
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<em>
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Cytogenetic location: 7q11.21
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:66,987,680-66,995,586 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<td rowspan="2">
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<span class="mim-font">
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7q11.21
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<td>
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<span class="mim-font">
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{Aplastic anemia, susceptibility to}
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</td>
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<td>
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<span class="mim-font">
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609135
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<span class="mim-font">
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<span class="mim-font">
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3
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<span class="mim-font">
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Shwachman-Diamond syndrome 1
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<span class="mim-font">
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260400
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<h4>
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<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>Boocock et al. (2003) screened 18 positional candidate genes in the critical region on chromosome 7q11 identified by linkage analysis for Shwachman-Diamond syndrome (SDS1; 260400), an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, hematologic dysfunction, and skeletal abnormalities. They discovered mutations associated with Shwachman-Diamond syndrome in an uncharacterized gene represented by the 1.6-kb cDNA clone FLJ10917 (GenBank AK001779). They designated the gene SBDS for 'Shwachman-Bodian-Diamond syndrome.' SBDS is a member of a highly conserved protein family, with orthologs in species ranging from archaea to vertebrates and plants. Indirect lines of evidence suggested that the orthologs may function in RNA metabolism. The predicted protein is 28.8 kD with a pI of 8.9. </p>
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<h4>
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<strong>Gene Structure</strong>
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<span class="mim-text-font">
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<p>Boocock et al. (2003) determined that the SBDS gene contains of 5 exons spanning 7.9 kb. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Boocock et al. (2003) mapped the SBDS gene to chromosome 7q11. SBDS and an adjacent gene reside in a block of 305 kb that is locally duplicated. The paralogous duplicon is located 5.8 Mb distally and contains an unprocessed pseudogene copy of SBDS designated SBDSP. The pseudogene transcript is 97% identical to SBDS and contains deletions and nucleotide changes that disrupt coding potential. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Austin et al. (2005) found that SBDS protein was present in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell cycle-dependent, with nucleolar localization during G1 and G2 and diffuse nuclear localization during S phase. The intranucleolar localization of SBDS provided further supportive evidence for its postulated role in the processing of ribosomal RNA (rRNA). </p><p>Ganapathi et al. (2007) presented in vitro evidence indicating that the SBDS gene is involved with ribosomal RNA. Nucleolar localization of SBDS was dependent on active ribosomal RNA transcription. Lymphoblast cell lines derived from SDS patients showed hypersensitivity to actinomycin D, which inhibits RNA polymerase I, indicating an underlying impairment of ribosome biogenesis. SBDS migrated with the 60S ribosomal precursor protein, and associated with the 28S subunit (see 180450) and nucleophosmin (see 164040). SBDS knockdown markedly decreased production of newly synthesized rRNA, although an imbalance of ribosomal subunits could not be detected. </p><p>Menne et al. (2007) identified the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, they identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1-delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. The data of Menne et al. (2007) linked defective 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition. </p><p>Austin et al. (2008) found that SBDS colocalized with mitotic spindles and bound to purified microtubules, thus preventing genomic instability, in wildtype human bone marrow stromal cells, lymphoblasts, and skin fibroblasts. Primary bone marrow stromal cells and lymphoblasts from SDS patients exhibited an increased incidence of abnormal mitoses. Depletion of the SBDS gene using siRNA in normal skin fibroblasts resulted in increased mitotic abnormalities and aneuploidy that accumulated over time. Treatment of primary cells from SDS patients with nocodazole, a microtubule destabilizing agent, led to increased mitotic arrest and apoptosis compared to treated wildtype cells. In addition, SDS patient cells were resistant to taxol, a microtubule stabilizing agent. These findings suggested that spindle instability in SDS contributes to bone marrow failure and leukemogenesis. </p><p>Vitiello et al. (2010) demonstrated that CLN3 (607042) interacts with SBDS. The protein-protein interaction was conserved between Btn1 and Sdo1, the respective S. cerevisiae orthologs of CLN3 and SBDS. It had been shown that deletion of Btn1 resulted in alterations in vacuolar pH and vacuolar (H+)-ATPase (V-ATPase)-dependent H+ transport and ATP hydrolysis. Vitiello et al. (2010) found that an Sdo1 deletion strain had decreased vacuolar pH and V-ATPase-dependent H+ transport and ATP hydrolysis; the alterations resulted from decreased V-ATPase subunit expression. Overexpression of Btn1 or the presence of ionophore carbonyl cyanide chlorophenil hydrazone (CCCP) caused decreased growth in yeast lacking Sdo1. In normal cells, overexpression of Btn1 mirrored the effect of CCCP, with both resulting in increased vacuolar pH due to alterations in the coupling of V-ATPase-dependent H+ transport and ATP hydrolysis. Vitiello et al. (2010) proposed that Sdo1 and SBDS work to regulate Btn1 and CLN3, respectively. </p><p>Raaijmakers et al. (2010) demonstrated that deletion of Dicer1 (606241) specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of hematopoiesis. Myelodysplasia resulted and acute myelogenous leukemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Shwachman-Bodian-Diamond syndrome, a human bone marrow failure and leukemia predisposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, Raaijmakers et al. (2010) concluded that perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation, and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, Raaijmakers et al. (2010) concluded that primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. </p><p>Using affinity capture and mass spectrometry, Ball et al. (2009) developed an SBDS interactome and reported SBDS binding partners with diverse molecular functions, notably components of the large ribosomal subunit and proteins involved in DNA metabolism. Reciprocal coimmunoprecipitation confirmed the interaction of SBDS with the large ribosomal subunit protein RPL4 (180479) and with DNA-PK (PRKDC; 600899) and RPA70 (RPA1; 179835), 2 proteins with critical roles in DNA repair. SBDS-depleted HEK293 cells were hypersensitive to multiple types of DNA damage as well as chemically induced endoplasmic reticulum stress, suggesting a role for SBDS in response to cellular stress. SBDS-dependent hypersensitivity of HEK293 cells to UV irradiation could be distinguished from a role of SBDS in translation. </p><p>Finch et al. (2011) showed that GTP and recombinant human SBDS and elongation factor-like-1 (EFL1, or EFTUD1) cooperated to trigger release of human EIF6 (602912) from pre60S ribosomes isolated from Sbds-deficient mouse livers. EFL1 and SBDS independently and noncooperatively bound to the 60S subunit in vitro. The 60S subunit activated the GTPase activity of EFL1, but SBDS was required to stimulate EIF6 release. Two SBDS mutants with different SDS-associated missense mutations varied in their ability to enhance 60S-dependent GTPase activity of EFL1, but neither triggered EIF6 release. Finch et al. (2011) concluded that SBDS and EFL1 catalyze translational activation and proposed that SDS is a ribosomopathy caused by uncoupling GTP hydrolysis from EIF6 release. </p><p>Garcia-Marquez et al. (2015) determined that the affinity of EFL1 for GTP was 10-fold lower than that calculated for GDP. Association of EFL1 with SBDS did not alter the affinity of EFL1 for GTP, but significantly reduced its dissociation constant for GDP. Thus, SBDS acted as a guanine nucleotide exchange factor (GEF) for EFL1, promoting activation of EFL1 by release of GDP. Garcia-Marquez et al. (2015) concluded that SBDS couples the energy liberated from the hydrolysis of GTP by EFL1 for release of EIF6 from the surface of the 60S ribosomal subunit. They further found that SBDS mutations found in patients with Shwachman-Diamond syndrome disrupted the interaction of SBDS with EFL1 and prevented SBDS regulation of the affinity of EFL1 toward guanine nucleotides. </p>
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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>Independently, Savchenko et al. (2005) and Shammas et al. (2005) determined the crystal structure of the Archaeglobus fulgidus ortholog of SBDS. They found that A. fulgidus Sbds assumes a highly conserved 3-domain structure consisting of an N-terminal domain with a novel 3-dimensional fold structure, a central domain containing a winged helix-turn-helix motif, and a C-terminal domain that shares structural homology with RNA-binding proteins. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Shwachman-Diamond Syndrome 1</em></strong></p><p>
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Boocock et al. (2003) reported mutations in the SBDS gene in affected individuals from 158 families with Shwachman-Diamond syndrome (SDS1; 260400). Gene conversion mutations accounted for 74.4% of alleles associated with Shwachman-Diamond syndrome (235 of 316). Observations indicated that gene conversion due to recombination between SBDS and its pseudogene had occurred. Conversion mutations were found in 89% of individuals with Shwachman-Diamond syndrome (141 of 158). Boocock et al. (2003) suggested that the conversion events are confined to a short segment spanning approximately 240 bp in exon 2. In 79 of 141 families with Shwachman-Diamond syndrome with conversion mutations, Boocock et al. (2003) found that affected individuals were compound heterozygous for 2 mutations in exon 2 of the SBDS gene: 183-184TA-CT (607444.0001) and 258+2T-C (IVS2DS+2T-C; 607444.0002). </p><p>In a study of Japanese patients with SDS, Nakashima et al. (2004) likewise found mutations in the SBDS gene caused by gene conversion. The sites of the gene conversion events varied, extending from intron 1 to exon 3. </p><p>Abnormalities in chromosome 7 have been reported in association with Shwachman-Diamond syndrome, especially an isochromosome i(7)(q10). In a 25-year-old patient with SDS who suffered from mild aplastic anemia but showed no signs of either myelodysplasia or leukemic transformation, Mellink et al. (2004) identified an isochromosome i(7)(q10) in the bone marrow and also identified 2 different mutations in the SBDS gene: the 183-184TA-CT mutation was present in 1 allele and the splice site mutation 258+2T-C was present in the other. The 2 mutations were the most commonly found in the study of Boocock et al. (2003). Mellink et al. (2004) concluded that the isochromosome 7q phenomenon may have a very indirect association with the pathogenesis of malignant transformation in SDS patients. It may be the first presentation of chromosome instability that could eventually result in more significant additional chromosomal aberrations involved in the clinical manifestation of acute myeloid leukemia and myelodysplasia syndrome. </p><p>Austin et al. (2005) characterized the SBDS protein expression and intracellular localization in 7 patients with Shwachman-Diamond syndrome and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. One patient, who was homozygous for the IVS2DS+2T-C mutation (607444.0002), expressed scant levels of SBDS protein. A second patient, harboring a missense mutation, expressed low levels of SBDS protein. A third patient, who carried no detectable gene mutations, expressed wildtype levels of SBDS protein, adding further support to the growing body of evidence for additional genes that might contribute to the pathogenesis of the disease phenotype. </p><p>By Sanger sequencing in 2 patients with SDS, Yamada et al. (2020) identified compound heterozygous mutations in the SBDS gene: c.258+2T-C on one allele and c.183-184TA-CT and c.201A-G on the other allele. However, the c.183-184TA-CT and c.201A-G variants were not identified by whole-exome sequencing in either patient. Yamada et al. (2020) concluded that these variants were missed by whole-exome analysis due to mismapping of reads resulting from the inability to discriminate between SBDS and the SBDSP1 pseudogene. All 3 variants were identified with transcriptome analysis via RNAseq in blood samples from both patients, leading Yamada et al. (2020) to conclude that RNA-seq is an effective assay for the diagnosis of SDS. </p><p><strong><em>Aplastic Anemia, Susceptibility to</em></strong></p><p>
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Calado et al. (2007) identified heterozygosity for the IVS2DS+2T-C mutation (607444.0002) in the SBDS gene in 4 of 91 unrelated patients with aplastic anemia (609135). These patients were younger on average (5 to 19 years) compared to other patients with aplastic anemia. Two mothers tested were carriers of the mutation; these 2 and another mother who was not tested had histories of subclinical mild anemia. Heterozygous mutation carriers had partial loss of SBDS protein expression, indicating haploinsufficiency. Although telomere shortening was observed in patients' granulocytes, lymphocytes had normal telomere length. None of the patients with aplastic anemia had pancreatic exocrine failure or skeletal anomalies as seen in SDS. One of the 4 probands was also heterozygous for a presumed pathogenic variant in the TERT gene (187270). The outcome of these patients was poor, with 2 deaths. Calado et al. (2007) concluded that SBDS deficiency predisposes to marrow failure by causing telomere shortening, thus indicating a role for SBDS in the maintenance of telomere length. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kuijpers et al. (2005) sequenced the SBDS gene in 20 unrelated patients with clinical SDS and identified mutations in 15 (75%), with identical compound heterozygosity in 11 patients (see 607444.0001 and 607444.0002). The authors examined hematologic parameters over 5 years of follow-up and observed persistent neutropenia in 43% in the absence of apoptosis and unrelated to chemotaxis defects or infection rate. Irrespective of the absolute neutrophil count in vivo, abnormal granulocyte-monocyte colony formation was observed in all patients with SDS tested (14 of 14), whereas erythroid and myeloid colony formation was less often affected (9 of 14). Cytogenetic aberrations occurred in 5 of 19 patients in the absence of myelodysplasia. Kuijpers et al. (2005) concluded that in patients with genetically proven SDS, a genotype/phenotype relationship does not exist in clinical and hematologic terms. </p>
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</span>
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<div>
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</div>
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<div>
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<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>Zhang et al. (2006) reported that loss of the Sbds gene resulted in early lethality in mice prior to embryonic day 6.5. Heterozygous mutant mice had a normal phenotype and were indistinguishable from wildtype littermates. </p><p>Finch et al. (2011) also found that Sbds deletion in mice was embryonic lethal. Sbds -/- mice showed prominent histologic abnormalities in liver, with disordered architecture between the portal triads and central veins, degenerative hepatocyte appearance, and scattered subcapsular areas of hepatocyte necrosis with an associated acute inflammatory reaction. Sbds-deleted liver extracts showed accumulation of free cytoplasmic 40S and 60S subunits and 43S initiation complexes that were stalled at the AUG start codon awaiting binding of 60S subunits, suggesting a ribosomal subunit-joining defect. </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>4 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 SHWACHMAN-DIAMOND SYNDROME 1</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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SBDS, LYS62TER
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<br />
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SNP: rs113993991, rs120074160,
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gnomAD: rs120074160,
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ClinVar: RCV000003346, RCV000255938, RCV000622680, RCV002496241, RCV003472961, RCV003904800, RCV004017224
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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 79 of 141 families with Shwachman-Diamond syndrome (SDS1; 260400) with conversion mutations, Boocock et al. (2003) found that affected individuals were compound heterozygous for 2 mutations in exon 2 of the SBDS gene: 183-184TA-CT and 258+2T-C (IVS2DS+2T-C; 607444.0002). The dinucleotide alteration 183-184TA-CT introduced an in-frame stop codon (lys62 to ter; K62X). The 258+2T-C mutation was predicted to disrupt the donor splice site of intron 2; it resulted in an 8-bp deletion consistent with use of an upstream cryptic splice donor site at position 251-252. The 258+2T-C and the resultant 8-bp deletion caused premature termination of the encoded protein by frameshift. In 44 families there was compound heterozygosity of 258+2T-C with another allele. In 7 families there was homozygosity for 258+2T-C. No incidence of homozygosity for 183-184TA-CT was observed. In 8 alleles of the SBDS gene found by Boocock et al. (2003) in patients with SDS, both the 183-184TA-CT and the 258+2T-C change were on the same allele. </p><p>In 11 patients with SDS, Kuijpers et al. (2005) identified compound heterozygosity for the K62X and 258+2T-C mutations in the SBDS gene. </p><p>By Sanger sequencing in 2 patients with SDS, Yamada et al. (2020) identified compound heterozygous mutations in the SBDS gene: c.183-184TA-CT and c.201A-G on one allele and c.258+2T-C the other allele. However, the c.183-184TA-CT and c.201A-G variants were not identified by whole-exome sequencing in either patient. Yamada et al. (2020) concluded that these variants were missed by whole-exome analysis due to mismapping of reads resulting from the inability to discriminate between SBDS and the SBDSP1 pseudogene. All 3 variants were identified with transcriptome analysis via RNAseq in blood samples from both patients, leading Yamada et al. (2020) to conclude that RNA-seq is an effective assay for the diagnosis of SDS. </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 SHWACHMAN-DIAMOND SYNDROME 1</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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APLASTIC ANEMIA, SUSCEPTIBILITY TO, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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SBDS, IVS2DS, T-C, +2
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<br />
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SNP: rs113993993,
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gnomAD: rs113993993,
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ClinVar: RCV000003347, RCV000003348, RCV000255013, RCV000506317, RCV000623539, RCV000626935, RCV000763594, RCV001270036, RCV002272008, RCV003407264
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Shwachman-Diamond Syndrome 1</em></strong></p><p>
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For discussion of the splice site mutation in the SBDS gene (IVS2DS+2T-C) that was found in compound heterozygous state in patients with Shwachman-Diamond syndrome (SDS1; 260400) by Boocock et al. (2003) and Kuijpers et al. (2005), see 607444.0001. Boocock et al. (2003) referred to this mutation as 258+2T-C. </p><p>Nakashima et al. (2004) identified this mutation in affected members of 4 Japanese families with SDS, making it the most prevalent mutation. Recurrent gene conversion was considered the most likely explanation for the recurrence, rather than founder effect. </p><p><strong><em>Aplastic Anemia, Susceptibility to</em></strong></p><p>
|
|
Calado et al. (2007) identified heterozygosity for the IVS2DS+2T-C mutation in 4 of 91 unrelated patients with aplastic anemia (609135). These patients were younger on average (5 to 19 years) compared to other patients with aplastic anemia. Two mothers tested were carriers of the mutation; these 2 and another mother who was not tested had histories of subclinical mild anemia. Heterozygous mutation carriers had partial loss of SBDS protein expression, indicating haploinsufficiency. Although telomere shortening was observed in patients' granulocytes, lymphocytes had normal telomere length. None of the patients with aplastic anemia had pancreatic exocrine failure or skeletal anomalies as seen in SDS. One of the 4 probands was also heterozygous for a presumed pathogenic variant in the TERT gene (187270). </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 SHWACHMAN-DIAMOND SYNDROME 1</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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SBDS, ASN8LYS
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<br />
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SNP: rs28942099,
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gnomAD: rs28942099,
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ClinVar: RCV000003349
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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 1 allele from individuals with Shwachman-Diamond syndrome (SDS1; 260400), Boocock et al. (2003) found a 24C-A transversion in the SBDS gene, predicted to result in an asn8-to-lys (N8K) amino acid change. The mutation on the other allele was not identified. </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 SHWACHMAN-DIAMOND SYNDROME 1</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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SBDS, 1-BP INS, 96A
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<br />
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ClinVar: RCV000003350
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of 4 Japanese families with Shwachman-Diamond syndrome (SDS1; 260400), Nakashima et al. (2004) found compound heterozygosity for 2 recurrent mutations in the SBDS gene: IVS2DS+2T-C (607444.0002) and a 1-bp insertion (96insA) in exon 1. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Austin, K. M., Gupta, M. L., Jr., Coats, S. A., Tulpule, A., Mostoslavsky, G., Balazs, A. B., Mulligan, R. C., Daley, G., Pellman, D., Shimamura, A.
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<strong>Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome.</strong>
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J. Clin. Invest. 118: 1511-1518, 2008.
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[PubMed: 18324336]
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[Full Text: https://doi.org/10.1172/JCI33764]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Austin, K. M., Leary, R. J., Shimamura, A.
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<strong>The Shwachman-Diamond SBDS protein localizes to the nucleolus.</strong>
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Blood 106: 1253-1258, 2005.
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[PubMed: 15860664]
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[Full Text: https://doi.org/10.1182/blood-2005-02-0807]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N.
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Kuijpers, T. W., Alders, M., Tool, A. T. J., Mellink, C., Roos, D., Hennekam, R. C. M.
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<strong>Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.</strong>
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Mellink, C. H. M., Alders, M., van der Lelie, H., Hennekam, R. H. C., Kuijpers, T. W.
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<strong>SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation?</strong>
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Cancer Genet. Cytogenet. 154: 144-149, 2004.
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Menne, T. F., Goyenechea, B., Sanchez-Puig, N., Wong, C. C., Tonkin, L. M., Ancliff, P. J., Brost, R. L., Costanzo, M., Boone, C., Warren, A. J.
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<strong>The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.</strong>
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Nakashima, E., Mabuchi, A., Makita, Y., Masuno, M., Ohashi, H., Nishimura, G., Ikegawa, S.
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<strong>Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.</strong>
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Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T.
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<strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong>
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Savchenko, A., Krogan, N., Cort, J. R., Evdokimova, E., Lew, J. M., Yee, A. A., Sanchez-Pulido, L., Andrade, M. A., Bochkarev, A., Watson, J. D., Kennedy, M. A., Greenblatt, J., Hughes, T., Arrowsmith, C. H., Rommens, J. M., Edwards, A. M.
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<strong>The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism.</strong>
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J. Biol. Chem. 280: 19213-19220, 2005.
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Shammas, C., Menne, T. F., Hilcenko, C., Michell, S. R., Goyenechea, B., Boocock, G. R. B., Durie, P. R., Rommens, J. M., Warren, A. J.
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<strong>Structural and mutational analysis of the SBDS protein family: insight into the leukemia-associated Shwachman-Diamond syndrome.</strong>
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Vitiello, S. P., Benedict, J. W., Padilla-Lopez, S., Pearce, D. A.
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<strong>Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model for Batten disease.</strong>
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Yamada, M., Uehara, T., Suzuki, H., Takenouchi, T., Inui, A., Ikemiyagi, M., Kamimaki, I., Kosaki, K.
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<strong>Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: mismapping due to the pseudogene SBDSP1.</strong>
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Zhang, S., Shi, M., Hui, C., Rommens, J. M.
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<strong>Loss of the mouse ortholog of the Shwachman-Diamond syndrome gene (Sbds) results in early embryonic lethality.</strong>
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