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Entry
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- *607642 - RETINOIC ACID-INDUCED GENE 1; RAI1
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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">*607642</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607642">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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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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<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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<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=ENSG00000108557;t=ENST00000353383" 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=10743" 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=607642" 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 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=ENSG00000108557;t=ENST00000353383" 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_030665,XM_017024027,XM_017024028,XM_047435149,XM_047435150,XM_047435151,XM_047435152,XM_047435153" 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_030665" 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=607642" 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=07406&isoform_id=07406_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/RAI1" 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/6599192,12053793,12053795,14017857,18203779,21740232,21740268,32480774,40807477,50400978,119576096,119576097,119576098,119576099,119576100,2217309430,2217309432,2217309434,2217309436,2217309438,2217309440,2217309442,2462552447,2462552449,2462552451,2462552453,2462552455,2462552457,2462552459" 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/Q7Z5J4" 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=10743" 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=ENSG00000108557;t=ENST00000353383" 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=RAI1" 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=RAI1" 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+10743" 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/RAI1" 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:10743" 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/10743" 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=chr17&hgg_gene=ENST00000724591.1&hgg_start=17681458&hgg_end=17811453&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 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:9834" 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:9834" 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/rai1" 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=607642[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=607642[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/RAI1/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/ENSG00000108557" 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=RAI1" 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=RAI1" 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=RAI1" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=RAI1&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/PA34188" 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:9834" 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/FBgn0034300.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:103291" 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/RAI1#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:103291" 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/10743/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002762/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=10743" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-101203-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:607642" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=RAI1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 401315004<br />
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<strong>ICD10CM:</strong> Q93.88<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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607642
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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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RETINOIC ACID-INDUCED GENE 1; RAI1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
RETINOIC ACID-INDUCIBLE 1
|
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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=RAI1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">RAI1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
|
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<strong>
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<em>
|
|
Cytogenetic location: <a href="/geneMap/17/270?start=-3&limit=10&highlight=270">17p11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:17681458-17811453&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'})">17:17,681,458-17,811,453</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>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
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</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/270?start=-3&limit=10&highlight=270">
|
|
17p11.2
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Smith-Magenis syndrome
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/182290"> 182290 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Isolated cases">IC</abbr>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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<p><a href="#10" class="mim-tip-reference" title="Seranski, P., Heiss, N. S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C. E., Lehrach, H., Poustka, A. <strong>Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.</strong> Genomics 56: 1-11, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10036180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10036180</a>] [<a href="https://doi.org/10.1006/geno.1998.5647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10036180">Seranski et al. (1999)</a> identified RAI1 within an unstable region of chromosome 17p11.2 that is associated with several neurologic disorders and malignant diseases. RT-PCR detected expression in all adult and fetal tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10036180" 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 cDNA selection, RT-PCR, and RACE using a fetal brain cDNA library, <a href="#11" class="mim-tip-reference" title="Seranski, P., Hoff, C., Radelof, U., Hennig, S., Reinhardt, R., Schwartz, C. E., Heiss, N. S., Poustka, A. <strong>RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients.</strong> Gene 270: 69-76, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11404004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11404004</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00415-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11404004">Seranski et al. (2001)</a> obtained a full-length RAI1 cDNA. The deduced 1,863-amino acid protein contains an N-terminal polyglutamine stretch that is encoded by a polymorphic CAG repeat. The C terminus contains a polyserine stretch and 3 RAI1 domains, which share similarity with transcription factor-20 (TCF20; <a href="/entry/603107">603107</a>). RAI1 has no potential membrane-spanning hydrophobic domains. Northern blot analysis revealed expression of several transcripts. An 8-kb transcript was expressed in all adult and fetal tissues and brain regions examined, except fetal liver. A 10-kb transcript was expressed weakly in heart, kidney, pancreas, stomach, thyroid, spinal cord, and lymph node. A 1.5-kb transcript was detected only in placenta. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11404004" 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 database analysis, <a href="#13" class="mim-tip-reference" title="Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A. <strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong> Genomics 82: 162-171, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837267</a>] [<a href="https://doi.org/10.1016/s0888-7543(03)00101-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837267">Toulouse et al. (2003)</a> determined that the CAG repeat was contained within the coding region of RAI1. By assembling ESTs and PCR of neuroblastoma cell line cDNA, cloned RAI1. The deduced protein contains 1,906 amino acids and shares 79% identity with mouse Rai1. <a href="#13" class="mim-tip-reference" title="Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A. <strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong> Genomics 82: 162-171, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837267</a>] [<a href="https://doi.org/10.1016/s0888-7543(03)00101-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837267">Toulouse et al. (2003)</a> noted that the polyglutamine tract encoded by the CAG repeat contains up to 18 glutamines in RAI1, and only 4 in the mouse homolog. Northern blot analysis confirmed expression of a single 8-kb transcript in all human tissues examined. Heart and brain showed highest expression. Northern blot analysis of individual brain regions detected similar expression in all regions analyzed except corpus callosum, where no expression was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837267" 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="#11" class="mim-tip-reference" title="Seranski, P., Hoff, C., Radelof, U., Hennig, S., Reinhardt, R., Schwartz, C. E., Heiss, N. S., Poustka, A. <strong>RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients.</strong> Gene 270: 69-76, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11404004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11404004</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00415-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11404004">Seranski et al. (2001)</a> determined that the RAI1 gene contains 8 exons and spans about 20 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11404004" 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="Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A. <strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong> Genomics 82: 162-171, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837267</a>] [<a href="https://doi.org/10.1016/s0888-7543(03)00101-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837267">Toulouse et al. (2003)</a> presented evidence that the RAI1 gene contains only 6 exons. In their model, the 5-prime untranslated region is encoded by 3 exons, and a significant CpG stretch is just upstream of exons 1 and 2. The promoter region contains binding sites for several regulatory proteins, including a retinoic acid-responsive element. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837267" 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="#10" class="mim-tip-reference" title="Seranski, P., Heiss, N. S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C. E., Lehrach, H., Poustka, A. <strong>Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.</strong> Genomics 56: 1-11, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10036180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10036180</a>] [<a href="https://doi.org/10.1006/geno.1998.5647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10036180">Seranski et al. (1999)</a> and <a href="#13" class="mim-tip-reference" title="Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A. <strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong> Genomics 82: 162-171, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837267</a>] [<a href="https://doi.org/10.1016/s0888-7543(03)00101-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837267">Toulouse et al. (2003)</a> mapped the RAI1 gene to chromosome 17p11.2, within the Smith-Magenis syndrome (SMS; <a href="/entry/182290">182290</a>) critical region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10036180+12837267" 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="Walz, K., Spencer, C., Kaasik, K., Lee, C. C., Lupski, J. R., Paylor, R. <strong>Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).</strong> Hum. Molec. Genet. 13: 367-378, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14709593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14709593</a>] [<a href="https://doi.org/10.1093/hmg/ddh044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14709593">Walz et al. (2004)</a> stated that the mouse Rai1 gene maps to a region of chromosome 11 that is syntenic with human chromosome 17p11.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14709593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using quantitative real-time PCR, <a href="#17" class="mim-tip-reference" title="Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H. <strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong> Am. J. Hum. Genet. 90: 941-949, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22578325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22578325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22578325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.04.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22578325">Williams et al. (2012)</a> found that knockdown of RAI1 via small interfering RNA in HEK293T cells reduced expression of CLOCK (<a href="/entry/601851">601851</a>), a transcription factor that heterodimerizes with BMAL1 (ARNTL; <a href="/entry/602550">602550</a>) to activate genes of the circadian feedback loop. Several CLOCK target genes and other components of the circadian feedback loop also showed dysregulation following knockdown of RAI1. Knockdown of RAI1 in U2OS-B cells reduced the circadian period length, as measured by BMAL1 expression. Human fibroblasts carrying a common SMS deletion, an atypical SMS deletion, or an RAI1 missense mutation (Q1562R; <a href="#0005">607642.0005</a>) exhibited dysregulated expression of core circadian genes. Chromatin immunoprecipitation, microarray analysis, and reporter gene assays revealed a functional RAI1-binding element in intron 1 of the CLOCK gene. <a href="#17" class="mim-tip-reference" title="Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H. <strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong> Am. J. Hum. Genet. 90: 941-949, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22578325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22578325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22578325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.04.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22578325">Williams et al. (2012)</a> concluded that RAI1 is a major positive regulator of CLOCK gene expression and is a circadian regulator. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22578325" 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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By FISH, <a href="#10" class="mim-tip-reference" title="Seranski, P., Heiss, N. S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C. E., Lehrach, H., Poustka, A. <strong>Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.</strong> Genomics 56: 1-11, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10036180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10036180</a>] [<a href="https://doi.org/10.1006/geno.1998.5647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10036180">Seranski et al. (1999)</a> determined that the RAI1 gene is deleted in SMS. <a href="#11" class="mim-tip-reference" title="Seranski, P., Hoff, C., Radelof, U., Hennig, S., Reinhardt, R., Schwartz, C. E., Heiss, N. S., Poustka, A. <strong>RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients.</strong> Gene 270: 69-76, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11404004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11404004</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00415-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11404004">Seranski et al. (2001)</a> confirmed heterozygous deletion of the RAI1 gene in all SMS patients analyzed. The CAG repeats of 13 SMS patients were sequenced, but no expansions, frameshifts, or point mutations were detected. In normal individuals and SMS patients, 5 different RAI1 alleles were detected by gel electrophoresis, and sequence analysis showed that the CAG repeats ranged in size from 36 to 42 bp. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10036180+11404004" 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>Smith-Magenis syndrome (SMS) is a mental retardation syndrome usually associated with deletions involving 17p11.2. Affected persons have characteristic behavioral abnormalities, including self-injurious behaviors and sleep disturbance, and distinct craniofacial and skeletal anomalies. <a href="#12" class="mim-tip-reference" title="Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H. <strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong> Nature Genet. 33: 466-468, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12652298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12652298</a>] [<a href="https://doi.org/10.1038/ng1126" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12652298">Slager et al. (2003)</a> identified dominant frameshift mutations (<a href="#0001">607642.0001</a>-<a href="#0003">607642.0003</a>) leading to premature termination of the RAI1 protein in 3 individuals who had phenotypic features consistent with SMS but did not have 17p11.2 deletions detectable by standard fluorescence in situ hybridization techniques. They suggested that SMS may be similar to previously described microdeletion syndromes in which a single gene is implicated in most of the features but other deleted genes may modify the overall phenotype. Haploinsufficiency of RAI1 is probably responsible for the behavioral, neurologic, otolaryngologic, and craniofacial features of the syndrome, but more variable features such as heart and renal defects are probably due to hemizygosity of other genes in the 17p11.2 region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12652298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bi, W., Saifi, G. M., Shaw, C. J., Walz, K., Fonseca, P., Wilson, M., Potocki, L., Lupski, J. R. <strong>Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome.</strong> Hum. Genet. 115: 515-524, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15565467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15565467</a>] [<a href="https://doi.org/10.1007/s00439-004-1187-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15565467">Bi et al. (2004)</a> reported 2 novel RAI1 mutations, 1 frameshift and 1 nonsense mutation, in 2 SMS patients without FISH-detectable deletions. Comparisons of the clinical features of these 2 patients, 3 of the previously reported RAI1 point mutation cases, and the patients with a common deletion suggested that most of the clinical features in SMS result from RAI1 mutation, although phenotypic variability exists even among individuals with RAI1 point mutations. Bioinformatics analyses of RAI1 and comparative genomics between human and mouse orthologs revealed a zinc finger-like plant homeodomain (PHD) at the C terminus that is conserved in the trithorax group of chromatin-based transcription regulators. These findings suggested that RAI1 is involved in transcriptional control through a multiprotein complex whose function may be altered in individuals with SMS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15565467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H. <strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong> J. Med. Genet. 42: 820-828, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>] [<a href="https://doi.org/10.1136/jmg.2005.031211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15788730">Girirajan et al. (2005)</a> performed mutation analysis of the RAI1 gene in 4 individuals with features consistent with SMS and without 17p11.2 deletions. Two patients were found to have small deletions in RAI1 resulting in frameshift and premature termination of the protein (<a href="#0006">607642.0006</a> and <a href="#0007">607642.0007</a>, respectively). Missense mutations (<a href="#0004">607642.0004</a> and <a href="#0005">607642.0005</a>, respectively) were identified in the other 2 patients. Orthologs across other genomes showed that these missense mutations occurred in identically conserved regions of the gene. The mutations were de novo. The patients' clinical features differed from those found in 17p11.2 deletions by general absence of short stature and lack of visceral anomalies. All 4 patients had developmental delay, reduced motor and cognitive skills, craniofacial and behavioral anomalies, and sleep disturbance. Seizures, not previously thought to be associated with RAI1 mutations, were observed in 1 patient. Thus, haploinsufficiency of the RAI1 gene is associated with most features of SMS, including craniofacial, behavioral, and neurologic signs and symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" 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="Bi, W., Saifi, G. M., Girirajan, S., Shi, X., Szomju, B., Firth, H., Magenis, R. E., Potocki, L., Elsea, S. H., Lupski, J. R. <strong>RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome.</strong> Am. J. Med. Genet. 140A: 2454-2463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041942</a>] [<a href="https://doi.org/10.1002/ajmg.a.31510" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17041942">Bi et al. (2006)</a> described 2 patients with SMS and point mutations in the RAI1 gene. One was a 9-year-old boy who had a de novo 1-bp deletion within a heptameric C-tract; the authors noted that of the 11 mutations reported in patients with SMS, the 5 frameshifts due to single basepair insertions or deletions all occurred within polyC tracts, and 2 were within the same heptameric C-tract. The other patient was a 5-year-old girl who was a compound heterozygote for a missense mutation inherited from her unaffected father and an 18-copy CAG repeat inherited from her mother, who had a history of ADHD. Her sister, who was obese and had emotional problems, carried the missense mutation but not the large CAG repeat; the missense mutation was not found in 120 ethnically matched controls. <a href="#2" class="mim-tip-reference" title="Bi, W., Saifi, G. M., Girirajan, S., Shi, X., Szomju, B., Firth, H., Magenis, R. E., Potocki, L., Elsea, S. H., Lupski, J. R. <strong>RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome.</strong> Am. J. Med. Genet. 140A: 2454-2463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041942</a>] [<a href="https://doi.org/10.1002/ajmg.a.31510" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17041942">Bi et al. (2006)</a> suggested that the apparent SMS phenotype observed in the female patient might result from the combination of the rare nucleotide change and the relatively large CAG repeat. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17041942" 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="Girirajan, S., Vlangos, C. N., Szomju, B. B., Edelman, E., Trevors, C. D., Dupuis, L., Nezarati, M., Bunyan, D. J., Elsea, S. H. <strong>Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum.</strong> Genet. Med. 8: 417-427, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16845274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16845274</a>] [<a href="https://doi.org/10.1097/01.gim.0000228215.32110.89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16845274">Girirajan et al. (2006)</a> reported the molecular and genotype-phenotype analyses of 31 patients with SMS who carry 17p11.2 deletions or intergenic mutations, respectively, and were compared for 30 characteristic features of the disorder by the Fisher exact test. Eight of the 31 individuals carried a common 3.5-Mb deletion, whereas 10 of 31 individuals carried smaller deletions, 2 individuals carried larger deletions, and 1 individual carried an atypical 17p11.2 deletion. Ten patients with nondeletion harbored a heterozygous mutation in RAI1. Phenotype comparison between patients with deletions and patients with RAI1 mutations showed that 21 of 30 SMS features are the result of haploinsufficiency of RAI1, whereas cardiac anomalies, speech and motor delay, hypotonia, short stature, and hearing loss are associated with 17p11.2 deletions rather than RAI1 mutations (P less than 0.05). Further, patients with smaller deletions show features similar to those with RAI1 mutations. <a href="#7" class="mim-tip-reference" title="Girirajan, S., Vlangos, C. N., Szomju, B. B., Edelman, E., Trevors, C. D., Dupuis, L., Nezarati, M., Bunyan, D. J., Elsea, S. H. <strong>Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum.</strong> Genet. Med. 8: 417-427, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16845274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16845274</a>] [<a href="https://doi.org/10.1097/01.gim.0000228215.32110.89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16845274">Girirajan et al. (2006)</a> concluded that although RAI1 is the primary gene responsible for most features of SMS, other genes within 17p11.2 contribute to the variable features and overall severity of the syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16845274" 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>Spinocerebellar Ataxia 2</em></strong></p><p>
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Spinocerebellar ataxia type 2 (SCA2; <a href="/entry/183090">183090</a>) is an autosomal dominant disorder caused by the expansion of a polymorphic (CAG)n tract, which is translated into an expanded polyglutamine tract in the ataxin-2 protein (ATX2; <a href="/entry/601517">601517</a>). Although repeat length and age at disease onset are inversely related, approximately 50% of the age at onset variance in SCA2 remained unexplained. Part of the remaining variance in polyglutamine disorders may be due to other familial factors. The ability of polyglutamine tracts to interact with each other, as well as the presence of intranuclear inclusions in other polyglutamine disorders, led <a href="#8" class="mim-tip-reference" title="Hayes, S., Turecki, G., Brisebois, K., Lopes-Cendes, I., Gaspar, C., Riess, O., Ranum, L. P. W., Pulst, S.-M., Rouleau, G. A. <strong>CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2).</strong> Hum. Molec. Genet. 9: 1753-1758, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10915763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10915763</a>] [<a href="https://doi.org/10.1093/hmg/9.12.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10915763">Hayes et al. (2000)</a> to hypothesize that other CAG-containing proteins may interact with expanded ataxin-2 and affect the rate of protein accumulation, and thus influence age at onset. To test this hypothesis, they used step-wise multiple linear regression to examine 10 CAG-containing genes for possible influences on SCA2 age at onset. They found that the RAI1 locus contributed an additional 4.1% of the variance in SCA2 age at onset after accounting for the effect of the SCA2 expanded repeat. No such effect was observed in the case of SCA3 (<a href="/entry/109150">109150</a>). The result implicated RAI1 as a possible contributor to SCA2 neurodegeneration and raised the possibility that other CAG-containing proteins may play a role in the pathogenesis of various polyglutamine disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10915763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Joober, R., Benkelfat, C., Toulouse, A., Lafreniere, R. G. A., Lal, S., Ajroud, S., Turecki, G., Bloom, D., Labelle, A., Lalonde, P., Alda, M., Morgan, K., Palmour, R., Rouleau, G. A. <strong>Analysis of 14 CAG repeat-containing genes in schizophrenia.</strong> Am. J. Med. Genet. 88: 694-699, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10581491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10581491</a>]" pmid="10581491">Joober et al. (1999)</a> identified a CAG repeat polymorphism that was associated with the severity of schizophrenia (<a href="/entry/181500">181500</a>) and patient response to neuroleptic medication. They found that schizophrenic patients who were able to respond to neuroleptic medication displayed a significantly shorter CAG repeat compared to controls. Nonresponders did not differ from controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10581491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using retrovirus-mediated chromosome engineering to create nested deletions of the mouse homolog to the SMS critical region, <a href="#18" class="mim-tip-reference" title="Yan, J., Keener, V. W., Bi, W., Walz, K., Bradley, A., Justice, M. J., Lupski, J. R. <strong>Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome.</strong> Hum. Molec. Genet. 13: 2613-2624, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459175</a>] [<a href="https://doi.org/10.1093/hmg/ddh288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459175">Yan et al. (2004)</a> constructed 3 lines of mice with 590- or 595-kb deletions, Df(11)17-1, Df(11)17-2, and Df(11)17-3. Both craniofacial abnormalities and obesity were observed, but the penetrance of the craniofacial phenotype was markedly reduced when compared with Df(11)17 mice, which have a 2-Mb deletion. The authors proposed that the loss of Rai1 may be responsible for the craniofacial abnormalities and obesity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459175" 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="Bi, W., Ohyama, T., Nakamura, H., Yan, J., Visvanathan, J., Justice, M. J., Lupski, J. R. <strong>Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome.</strong> Hum. Molec. Genet. 14: 983-995, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15746153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15746153</a>] [<a href="https://doi.org/10.1093/hmg/ddi085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15746153">Bi et al. (2005)</a> generated a null RAI1 allele in mice. Obesity and craniofacial abnormalities were observed in Rai1 +/- mice, but the penetrance of craniofacial anomalies was further reduced in Rai1 +/- mice compared with Df(11)17-1 or Df(11)17 mice. Most Rai1 -/- mice died during gastrulation and organogenesis, and survivors were growth retarded and displayed malformations in both the craniofacial and the axial skeleton. Using Rai1-fusion constructs, the authors showed that Rai1 is translocated to the nucleus and has transactivation activity. <a href="#1" class="mim-tip-reference" title="Bi, W., Ohyama, T., Nakamura, H., Yan, J., Visvanathan, J., Justice, M. J., Lupski, J. R. <strong>Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome.</strong> Hum. Molec. Genet. 14: 983-995, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15746153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15746153</a>] [<a href="https://doi.org/10.1093/hmg/ddi085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15746153">Bi et al. (2005)</a> concluded that Rai1 functions as a transcriptional regulator and may be important for embryonic and postnatal development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15746153" 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="Walz, K., Spencer, C., Kaasik, K., Lee, C. C., Lupski, J. R., Paylor, R. <strong>Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).</strong> Hum. Molec. Genet. 13: 367-378, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14709593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14709593</a>] [<a href="https://doi.org/10.1093/hmg/ddh044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14709593">Walz et al. (2004)</a> found that heterozygous Df(11)17 mice displayed an average circadian period that was significantly shorter than that of wildtype littermates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14709593" 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>Mice with a heterozygous duplication, Dp(11)17, of the region on mouse chromosome 11 that is syntenic to human chromosome 17 are underweight and show behavioral anomalies such as impaired contextual fear conditioning (Walz et al. (<a href="#14" class="mim-tip-reference" title="Walz, K., Caratini-Rivera, S., Bi, W., Fonseca, P., Mansouri, D. L., Lynch, J., Vogel, H., Noebels, J. L., Bradley, A., Lupski, J. R. <strong>Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance.</strong> Molec. Cell. Biol. 23: 3646-3655, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724422[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.23.10.3646-3655.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12724422">2003</a>, <a href="#16" class="mim-tip-reference" title="Walz, K., Spencer, C., Kaasik, K., Lee, C. C., Lupski, J. R., Paylor, R. <strong>Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).</strong> Hum. Molec. Genet. 13: 367-378, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14709593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14709593</a>] [<a href="https://doi.org/10.1093/hmg/ddh044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14709593">2004</a>)). <a href="#15" class="mim-tip-reference" title="Walz, K., Paylor, R., Yan, J., Bi, W., Lupski, J. R. <strong>Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2).</strong> J. Clin. Invest. 116: 3035-3041, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17024248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17024248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17024248[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/JCI28953" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17024248">Walz et al. (2006)</a> generated compound heterozygous mice with a Dp(11)17 allele and a null Rai1 allele, thus resulting in normal disomic gene dosage of Rai1. Normal Rai1 dosage rescued many of the phenotypes observed in heterozygous Dp(11)17 mice, who have 3 copies of the gene, including normalization of body weight and partial normalization of behavior. The phenotype was rescued despite altered trisomic copy number of the other 18 or so genes in the region. <a href="#15" class="mim-tip-reference" title="Walz, K., Paylor, R., Yan, J., Bi, W., Lupski, J. R. <strong>Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2).</strong> J. Clin. Invest. 116: 3035-3041, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17024248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17024248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17024248[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/JCI28953" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17024248">Walz et al. (2006)</a> concluded that duplication of Rai1 is responsible for decreased body weight in Dp(11)17 mice and that Rai1 is a dosage-sensitive gene involved in body weight control and complex behavioral responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14709593+12724422+17024248" 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="Girirajan, S., Patel, N., Slager, R. E., Tokarz, M. E., Bucan, M., Wiley, J. L., Elsea, S. H. <strong>How much is too much? Phenotypic consequences of Rai1 overexpression in mice.</strong> Europ. J. Hum. Genet. 16: 941-954, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285828</a>] [<a href="https://doi.org/10.1038/ejhg.2008.21" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285828">Girirajan et al. (2008)</a> generated transgenic mice with 4 and 6 copies of the Rai1 gene. The mice showed growth retardation, increased locomotor activity, impaired sensorimotor activity, and abnormal anxiety-related behavior compared to wildtype littermates. Rai1-transgenic mice had an altered gait, decreased forelimb grip strength, and a dominant social behavior. There was a dose-dependent exacerbation of the phenotype, including extreme growth retardation, severe neurologic deficits, and increased hyperactivity in mice with higher Rai1 expression. <a href="#6" class="mim-tip-reference" title="Girirajan, S., Patel, N., Slager, R. E., Tokarz, M. E., Bucan, M., Wiley, J. L., Elsea, S. H. <strong>How much is too much? Phenotypic consequences of Rai1 overexpression in mice.</strong> Europ. J. Hum. Genet. 16: 941-954, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285828</a>] [<a href="https://doi.org/10.1038/ejhg.2008.21" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285828">Girirajan et al. (2008)</a> concluded that Rai1 dosage has major consequences on molecular processes involved in growth, development, and neurologic and behavioral functions, providing evidence for several dosage-thresholds for phenotypic manifestations in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Burns, B., Schmidt, K., Williams, S. R., Kim, S., Girirajan, S., Elsea, S. H. <strong>Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome.</strong> Hum. Molec. Genet. 19: 4026-4042, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20663924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20663924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20663924[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/ddq317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20663924">Burns et al. (2010)</a> investigated the growth and obesity phenotype in a mouse model haploinsufficient for Rai1. Rai1 +/- mice were hyperphagic, had an impaired satiety response, and had an altered abdominal and subcutaneous fat distribution, with Rai1 +/- female mice having a higher proportion of abdominal fat when compared with wildtype female mice. Brain-derived neurotrophic factor (BDNF; <a href="/entry/113505">113505</a>), a gene associated with hyperphagia and obesity, was downregulated in the Rai1 +/- mouse hypothalamus, and reporter studies showed that RAI1 directly regulated the expression of BDNF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20663924" 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 quantitative real-time PCR, <a href="#17" class="mim-tip-reference" title="Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H. <strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong> Am. J. Hum. Genet. 90: 941-949, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22578325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22578325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22578325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.04.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22578325">Williams et al. (2012)</a> found that Rai1 +/- mouse hypothalamus showed dysregulated expression of Clock and other circadian genes during light and dark phases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22578325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=607642[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In a person with Smith-Magenis syndrome (<a href="/entry/182290">182290</a>), <a href="#12" class="mim-tip-reference" title="Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H. <strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong> Nature Genet. 33: 466-468, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12652298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12652298</a>] [<a href="https://doi.org/10.1038/ng1126" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12652298">Slager et al. (2003)</a> identified deletion on 1 RAI1 allele of a single cytosine in a run of 6 cytosines. The 4929delC on the coding strand produced a frameshift, introducing 74 incorrect amino acids and truncating protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12652298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a person with Smith-Magenis syndrome (<a href="/entry/182290">182290</a>), <a href="#12" class="mim-tip-reference" title="Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H. <strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong> Nature Genet. 33: 466-468, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12652298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12652298</a>] [<a href="https://doi.org/10.1038/ng1126" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12652298">Slager et al. (2003)</a> observed deletion of 1 C from a run of 4 Cs ending at nucleotide position 1308 in exon 3 of RAI1. This deletion caused a frameshift that incorporated 34 incorrect amino acids beginning at amino acid position 437, followed by a stop codon and premature termination of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12652298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a person with Smith-Magenis syndrome (<a href="/entry/182290">182290</a>), <a href="#12" class="mim-tip-reference" title="Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H. <strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong> Nature Genet. 33: 466-468, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12652298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12652298</a>] [<a href="https://doi.org/10.1038/ng1126" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12652298">Slager et al. (2003)</a> found a deletion of 29 basepairs in exon 3 of the RAI gene on 1 allele. This deletion produced a frameshift that introduced 8 incorrect amino acids followed by a stop codon, truncating the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12652298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894633 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894633;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/rs104894633?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=rs104894633" 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=rs104894633" 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=RCV000003083 OR RCV002054412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003083, RCV002054412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003083...</a>
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<p>In a 17-year-old adopted boy of northern European and Jewish ancestry with features considered consistent with SMS (<a href="/entry/182290">182290</a>), <a href="#5" class="mim-tip-reference" title="Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H. <strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong> J. Med. Genet. 42: 820-828, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>] [<a href="https://doi.org/10.1136/jmg.2005.031211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15788730">Girirajan et al. (2005)</a> detected a heterozygous 5423G-A mutation in the RAI1 gene underlying a serine-to-asparagine change at amino acid 1808 (S1808N). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 SMITH-MAGENIS SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894634 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894634;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=rs104894634" 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=rs104894634" 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=RCV000003084" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003084" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003084</a>
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<p>In an 11-year-old white girl with mental retardation, progressive speech delay, stereotypic behavior, intractable complex seizures, and facial dysmorphism consistent with a diagnosis of Smith-Magenis syndrome (<a href="/entry/182290">182290</a>), <a href="#5" class="mim-tip-reference" title="Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H. <strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong> J. Med. Genet. 42: 820-828, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>] [<a href="https://doi.org/10.1136/jmg.2005.031211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15788730">Girirajan et al. (2005)</a> described a missense mutation in the RAI1 protein, gln1562 to arg (Q1562R), resulting from a heterozygous adenine-to-guanine transition at nucleotide 4685. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" 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 quantitative real-time PCR, <a href="#17" class="mim-tip-reference" title="Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H. <strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong> Am. J. Hum. Genet. 90: 941-949, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22578325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22578325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22578325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.04.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22578325">Williams et al. (2012)</a> showed that fibroblasts carrying the Q1562R mutation showed dysregulated expression of genes required for circadian rhythmicity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22578325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 SMITH-MAGENIS SYNDROME</strong>
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RAI1, 1-BP DEL, 3801C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1598092236 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1598092236;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=rs1598092236" 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=rs1598092236" 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=RCV000003085" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003085" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003085</a>
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<p>In a 14-year-old boy of European descent with features considered consistent with SMS (<a href="/entry/182290">182290</a>), <a href="#5" class="mim-tip-reference" title="Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H. <strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong> J. Med. Genet. 42: 820-828, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>] [<a href="https://doi.org/10.1136/jmg.2005.031211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15788730">Girirajan et al. (2005)</a> found a 1-bp deletion in the RAI1 gene, 3801delC, in heterozygous state. The deletion resulted in a frameshift starting at amino acid 1267, leading to misincorporation of 46 amino acids and a downstream stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0007 SMITH-MAGENIS SYNDROME</strong>
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RAI1, 19-BP DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000003086" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003086" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003086</a>
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<p><a href="#5" class="mim-tip-reference" title="Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H. <strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong> J. Med. Genet. 42: 820-828, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>] [<a href="https://doi.org/10.1136/jmg.2005.031211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15788730">Girirajan et al. (2005)</a> found that a 19-year-old woman of European descent with features consistent with SMS (<a href="/entry/182290">182290</a>) had a 19-bp deletion in the RAI1 gene (253del19). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Bi2005" class="mim-anchor"></a>
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Bi, W., Ohyama, T., Nakamura, H., Yan, J., Visvanathan, J., Justice, M. J., Lupski, J. R.
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<strong>Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome.</strong>
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Hum. Molec. Genet. 14: 983-995, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15746153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15746153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15746153" 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/ddi085" target="_blank">Full Text</a>]
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Bi, W., Saifi, G. M., Girirajan, S., Shi, X., Szomju, B., Firth, H., Magenis, R. E., Potocki, L., Elsea, S. H., Lupski, J. R.
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<strong>RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome.</strong>
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Am. J. Med. Genet. 140A: 2454-2463, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17041942" 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.31510" target="_blank">Full Text</a>]
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Bi, W., Saifi, G. M., Shaw, C. J., Walz, K., Fonseca, P., Wilson, M., Potocki, L., Lupski, J. R.
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<strong>Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome.</strong>
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Hum. Genet. 115: 515-524, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15565467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15565467</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15565467" 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/s00439-004-1187-6" target="_blank">Full Text</a>]
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Burns, B., Schmidt, K., Williams, S. R., Kim, S., Girirajan, S., Elsea, S. H.
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<strong>Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome.</strong>
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Hum. Molec. Genet. 19: 4026-4042, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20663924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20663924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20663924[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=20663924" 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/ddq317" target="_blank">Full Text</a>]
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Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H.
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<strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong>
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J. Med. Genet. 42: 820-828, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15788730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15788730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15788730" 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/10.1136/jmg.2005.031211" target="_blank">Full Text</a>]
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Girirajan, S., Patel, N., Slager, R. E., Tokarz, M. E., Bucan, M., Wiley, J. L., Elsea, S. H.
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<strong>How much is too much? Phenotypic consequences of Rai1 overexpression in mice.</strong>
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Europ. J. Hum. Genet. 16: 941-954, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2008.21" target="_blank">Full Text</a>]
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Girirajan, S., Vlangos, C. N., Szomju, B. B., Edelman, E., Trevors, C. D., Dupuis, L., Nezarati, M., Bunyan, D. J., Elsea, S. H.
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<strong>Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum.</strong>
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Genet. Med. 8: 417-427, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16845274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16845274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16845274" 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/10.1097/01.gim.0000228215.32110.89" target="_blank">Full Text</a>]
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<a id="Hayes2000" class="mim-anchor"></a>
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Hayes, S., Turecki, G., Brisebois, K., Lopes-Cendes, I., Gaspar, C., Riess, O., Ranum, L. P. W., Pulst, S.-M., Rouleau, G. A.
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<strong>CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2).</strong>
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Hum. Molec. Genet. 9: 1753-1758, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10915763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10915763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10915763" 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/9.12.1753" target="_blank">Full Text</a>]
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<a id="Joober1999" class="mim-anchor"></a>
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Joober, R., Benkelfat, C., Toulouse, A., Lafreniere, R. G. A., Lal, S., Ajroud, S., Turecki, G., Bloom, D., Labelle, A., Lalonde, P., Alda, M., Morgan, K., Palmour, R., Rouleau, G. A.
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<a id="Seranski1999" class="mim-anchor"></a>
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Seranski, P., Heiss, N. S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C. E., Lehrach, H., Poustka, A.
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<strong>Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.</strong>
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Genomics 56: 1-11, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10036180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10036180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10036180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1998.5647" target="_blank">Full Text</a>]
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<a id="Seranski2001" class="mim-anchor"></a>
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Seranski, P., Hoff, C., Radelof, U., Hennig, S., Reinhardt, R., Schwartz, C. E., Heiss, N. S., Poustka, A.
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<strong>RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients.</strong>
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Gene 270: 69-76, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11404004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11404004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11404004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0378-1119(01)00415-2" target="_blank">Full Text</a>]
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Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H.
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<strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong>
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Nature Genet. 33: 466-468, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12652298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12652298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12652298" 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/ng1126" target="_blank">Full Text</a>]
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Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A.
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<strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong>
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Genomics 82: 162-171, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837267</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837267" 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/s0888-7543(03)00101-0" target="_blank">Full Text</a>]
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Walz, K., Caratini-Rivera, S., Bi, W., Fonseca, P., Mansouri, D. L., Lynch, J., Vogel, H., Noebels, J. L., Bradley, A., Lupski, J. R.
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<strong>Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance.</strong>
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Molec. Cell. Biol. 23: 3646-3655, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724422[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=12724422" 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.23.10.3646-3655.2003" target="_blank">Full Text</a>]
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Walz, K., Paylor, R., Yan, J., Bi, W., Lupski, J. R.
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<strong>Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2).</strong>
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J. Clin. Invest. 116: 3035-3041, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17024248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17024248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17024248[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=17024248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI28953" target="_blank">Full Text</a>]
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<a id="Walz2004" class="mim-anchor"></a>
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Walz, K., Spencer, C., Kaasik, K., Lee, C. C., Lupski, J. R., Paylor, R.
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<strong>Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).</strong>
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Hum. Molec. Genet. 13: 367-378, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14709593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14709593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14709593" 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/ddh044" target="_blank">Full Text</a>]
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Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H.
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<strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong>
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Am. J. Hum. Genet. 90: 941-949, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22578325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22578325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22578325[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=22578325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2012.04.013" target="_blank">Full Text</a>]
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Yan, J., Keener, V. W., Bi, W., Walz, K., Bradley, A., Justice, M. J., Lupski, J. R.
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<strong>Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome.</strong>
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Hum. Molec. Genet. 13: 2613-2624, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459175" 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/ddh288" target="_blank">Full Text</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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George E. Tiller - updated : 06/21/2017
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Patricia A. Hartz - updated : 7/26/2012<br>Ada Hamosh - updated : 10/12/2010<br>Cassandra L. Kniffin - updated : 8/19/2008<br>George E. Tiller - updated : 2/7/2008<br>Ada Hamosh - updated : 7/25/2007<br>George E. Tiller - updated : 6/13/2007<br>Marla J. F. O'Neill - updated : 2/2/2007<br>Cassandra L. Kniffin - updated : 12/8/2006<br>Victor A. McKusick - updated : 6/22/2006<br>Victor A. McKusick - updated : 4/27/2005<br>Patricia A. Hartz - updated : 7/22/2003<br>Victor A. McKusick - updated : 3/21/2003
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Patricia A. Hartz : 3/20/2003
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carol : 09/22/2022
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<h3>
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<span class="mim-font">
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<strong>*</strong> 607642
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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RETINOIC ACID-INDUCED GENE 1; RAI1
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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RETINOIC ACID-INDUCIBLE 1
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: RAI1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 401315004;
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<strong>ICD10CM:</strong> Q93.88;
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17p11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:17,681,458-17,811,453 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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17p11.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Smith-Magenis syndrome
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</span>
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</td>
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<td>
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<span class="mim-font">
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182290
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Isolated cases
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Seranski et al. (1999) identified RAI1 within an unstable region of chromosome 17p11.2 that is associated with several neurologic disorders and malignant diseases. RT-PCR detected expression in all adult and fetal tissues examined. </p><p>By cDNA selection, RT-PCR, and RACE using a fetal brain cDNA library, Seranski et al. (2001) obtained a full-length RAI1 cDNA. The deduced 1,863-amino acid protein contains an N-terminal polyglutamine stretch that is encoded by a polymorphic CAG repeat. The C terminus contains a polyserine stretch and 3 RAI1 domains, which share similarity with transcription factor-20 (TCF20; 603107). RAI1 has no potential membrane-spanning hydrophobic domains. Northern blot analysis revealed expression of several transcripts. An 8-kb transcript was expressed in all adult and fetal tissues and brain regions examined, except fetal liver. A 10-kb transcript was expressed weakly in heart, kidney, pancreas, stomach, thyroid, spinal cord, and lymph node. A 1.5-kb transcript was detected only in placenta. </p><p>By database analysis, Toulouse et al. (2003) determined that the CAG repeat was contained within the coding region of RAI1. By assembling ESTs and PCR of neuroblastoma cell line cDNA, cloned RAI1. The deduced protein contains 1,906 amino acids and shares 79% identity with mouse Rai1. Toulouse et al. (2003) noted that the polyglutamine tract encoded by the CAG repeat contains up to 18 glutamines in RAI1, and only 4 in the mouse homolog. Northern blot analysis confirmed expression of a single 8-kb transcript in all human tissues examined. Heart and brain showed highest expression. Northern blot analysis of individual brain regions detected similar expression in all regions analyzed except corpus callosum, where no expression was observed. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Seranski et al. (2001) determined that the RAI1 gene contains 8 exons and spans about 20 kb. </p><p>Toulouse et al. (2003) presented evidence that the RAI1 gene contains only 6 exons. In their model, the 5-prime untranslated region is encoded by 3 exons, and a significant CpG stretch is just upstream of exons 1 and 2. The promoter region contains binding sites for several regulatory proteins, including a retinoic acid-responsive element. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Seranski et al. (1999) and Toulouse et al. (2003) mapped the RAI1 gene to chromosome 17p11.2, within the Smith-Magenis syndrome (SMS; 182290) critical region. </p><p>Walz et al. (2004) stated that the mouse Rai1 gene maps to a region of chromosome 11 that is syntenic with human chromosome 17p11.2. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using quantitative real-time PCR, Williams et al. (2012) found that knockdown of RAI1 via small interfering RNA in HEK293T cells reduced expression of CLOCK (601851), a transcription factor that heterodimerizes with BMAL1 (ARNTL; 602550) to activate genes of the circadian feedback loop. Several CLOCK target genes and other components of the circadian feedback loop also showed dysregulation following knockdown of RAI1. Knockdown of RAI1 in U2OS-B cells reduced the circadian period length, as measured by BMAL1 expression. Human fibroblasts carrying a common SMS deletion, an atypical SMS deletion, or an RAI1 missense mutation (Q1562R; 607642.0005) exhibited dysregulated expression of core circadian genes. Chromatin immunoprecipitation, microarray analysis, and reporter gene assays revealed a functional RAI1-binding element in intron 1 of the CLOCK gene. Williams et al. (2012) concluded that RAI1 is a major positive regulator of CLOCK gene expression and is a circadian regulator. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Smith-Magenis Syndrome</em></strong></p><p>
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By FISH, Seranski et al. (1999) determined that the RAI1 gene is deleted in SMS. Seranski et al. (2001) confirmed heterozygous deletion of the RAI1 gene in all SMS patients analyzed. The CAG repeats of 13 SMS patients were sequenced, but no expansions, frameshifts, or point mutations were detected. In normal individuals and SMS patients, 5 different RAI1 alleles were detected by gel electrophoresis, and sequence analysis showed that the CAG repeats ranged in size from 36 to 42 bp. </p><p>Smith-Magenis syndrome (SMS) is a mental retardation syndrome usually associated with deletions involving 17p11.2. Affected persons have characteristic behavioral abnormalities, including self-injurious behaviors and sleep disturbance, and distinct craniofacial and skeletal anomalies. Slager et al. (2003) identified dominant frameshift mutations (607642.0001-607642.0003) leading to premature termination of the RAI1 protein in 3 individuals who had phenotypic features consistent with SMS but did not have 17p11.2 deletions detectable by standard fluorescence in situ hybridization techniques. They suggested that SMS may be similar to previously described microdeletion syndromes in which a single gene is implicated in most of the features but other deleted genes may modify the overall phenotype. Haploinsufficiency of RAI1 is probably responsible for the behavioral, neurologic, otolaryngologic, and craniofacial features of the syndrome, but more variable features such as heart and renal defects are probably due to hemizygosity of other genes in the 17p11.2 region. </p><p>Bi et al. (2004) reported 2 novel RAI1 mutations, 1 frameshift and 1 nonsense mutation, in 2 SMS patients without FISH-detectable deletions. Comparisons of the clinical features of these 2 patients, 3 of the previously reported RAI1 point mutation cases, and the patients with a common deletion suggested that most of the clinical features in SMS result from RAI1 mutation, although phenotypic variability exists even among individuals with RAI1 point mutations. Bioinformatics analyses of RAI1 and comparative genomics between human and mouse orthologs revealed a zinc finger-like plant homeodomain (PHD) at the C terminus that is conserved in the trithorax group of chromatin-based transcription regulators. These findings suggested that RAI1 is involved in transcriptional control through a multiprotein complex whose function may be altered in individuals with SMS. </p><p>Girirajan et al. (2005) performed mutation analysis of the RAI1 gene in 4 individuals with features consistent with SMS and without 17p11.2 deletions. Two patients were found to have small deletions in RAI1 resulting in frameshift and premature termination of the protein (607642.0006 and 607642.0007, respectively). Missense mutations (607642.0004 and 607642.0005, respectively) were identified in the other 2 patients. Orthologs across other genomes showed that these missense mutations occurred in identically conserved regions of the gene. The mutations were de novo. The patients' clinical features differed from those found in 17p11.2 deletions by general absence of short stature and lack of visceral anomalies. All 4 patients had developmental delay, reduced motor and cognitive skills, craniofacial and behavioral anomalies, and sleep disturbance. Seizures, not previously thought to be associated with RAI1 mutations, were observed in 1 patient. Thus, haploinsufficiency of the RAI1 gene is associated with most features of SMS, including craniofacial, behavioral, and neurologic signs and symptoms. </p><p>Bi et al. (2006) described 2 patients with SMS and point mutations in the RAI1 gene. One was a 9-year-old boy who had a de novo 1-bp deletion within a heptameric C-tract; the authors noted that of the 11 mutations reported in patients with SMS, the 5 frameshifts due to single basepair insertions or deletions all occurred within polyC tracts, and 2 were within the same heptameric C-tract. The other patient was a 5-year-old girl who was a compound heterozygote for a missense mutation inherited from her unaffected father and an 18-copy CAG repeat inherited from her mother, who had a history of ADHD. Her sister, who was obese and had emotional problems, carried the missense mutation but not the large CAG repeat; the missense mutation was not found in 120 ethnically matched controls. Bi et al. (2006) suggested that the apparent SMS phenotype observed in the female patient might result from the combination of the rare nucleotide change and the relatively large CAG repeat. </p><p>Girirajan et al. (2006) reported the molecular and genotype-phenotype analyses of 31 patients with SMS who carry 17p11.2 deletions or intergenic mutations, respectively, and were compared for 30 characteristic features of the disorder by the Fisher exact test. Eight of the 31 individuals carried a common 3.5-Mb deletion, whereas 10 of 31 individuals carried smaller deletions, 2 individuals carried larger deletions, and 1 individual carried an atypical 17p11.2 deletion. Ten patients with nondeletion harbored a heterozygous mutation in RAI1. Phenotype comparison between patients with deletions and patients with RAI1 mutations showed that 21 of 30 SMS features are the result of haploinsufficiency of RAI1, whereas cardiac anomalies, speech and motor delay, hypotonia, short stature, and hearing loss are associated with 17p11.2 deletions rather than RAI1 mutations (P less than 0.05). Further, patients with smaller deletions show features similar to those with RAI1 mutations. Girirajan et al. (2006) concluded that although RAI1 is the primary gene responsible for most features of SMS, other genes within 17p11.2 contribute to the variable features and overall severity of the syndrome. </p><p><strong><em>Spinocerebellar Ataxia 2</em></strong></p><p>
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Spinocerebellar ataxia type 2 (SCA2; 183090) is an autosomal dominant disorder caused by the expansion of a polymorphic (CAG)n tract, which is translated into an expanded polyglutamine tract in the ataxin-2 protein (ATX2; 601517). Although repeat length and age at disease onset are inversely related, approximately 50% of the age at onset variance in SCA2 remained unexplained. Part of the remaining variance in polyglutamine disorders may be due to other familial factors. The ability of polyglutamine tracts to interact with each other, as well as the presence of intranuclear inclusions in other polyglutamine disorders, led Hayes et al. (2000) to hypothesize that other CAG-containing proteins may interact with expanded ataxin-2 and affect the rate of protein accumulation, and thus influence age at onset. To test this hypothesis, they used step-wise multiple linear regression to examine 10 CAG-containing genes for possible influences on SCA2 age at onset. They found that the RAI1 locus contributed an additional 4.1% of the variance in SCA2 age at onset after accounting for the effect of the SCA2 expanded repeat. No such effect was observed in the case of SCA3 (109150). The result implicated RAI1 as a possible contributor to SCA2 neurodegeneration and raised the possibility that other CAG-containing proteins may play a role in the pathogenesis of various polyglutamine disorders. </p><p>Joober et al. (1999) identified a CAG repeat polymorphism that was associated with the severity of schizophrenia (181500) and patient response to neuroleptic medication. They found that schizophrenic patients who were able to respond to neuroleptic medication displayed a significantly shorter CAG repeat compared to controls. Nonresponders did not differ from controls. </p>
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</span>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using retrovirus-mediated chromosome engineering to create nested deletions of the mouse homolog to the SMS critical region, Yan et al. (2004) constructed 3 lines of mice with 590- or 595-kb deletions, Df(11)17-1, Df(11)17-2, and Df(11)17-3. Both craniofacial abnormalities and obesity were observed, but the penetrance of the craniofacial phenotype was markedly reduced when compared with Df(11)17 mice, which have a 2-Mb deletion. The authors proposed that the loss of Rai1 may be responsible for the craniofacial abnormalities and obesity. </p><p>Bi et al. (2005) generated a null RAI1 allele in mice. Obesity and craniofacial abnormalities were observed in Rai1 +/- mice, but the penetrance of craniofacial anomalies was further reduced in Rai1 +/- mice compared with Df(11)17-1 or Df(11)17 mice. Most Rai1 -/- mice died during gastrulation and organogenesis, and survivors were growth retarded and displayed malformations in both the craniofacial and the axial skeleton. Using Rai1-fusion constructs, the authors showed that Rai1 is translocated to the nucleus and has transactivation activity. Bi et al. (2005) concluded that Rai1 functions as a transcriptional regulator and may be important for embryonic and postnatal development. </p><p>Walz et al. (2004) found that heterozygous Df(11)17 mice displayed an average circadian period that was significantly shorter than that of wildtype littermates. </p><p>Mice with a heterozygous duplication, Dp(11)17, of the region on mouse chromosome 11 that is syntenic to human chromosome 17 are underweight and show behavioral anomalies such as impaired contextual fear conditioning (Walz et al. (2003, 2004)). Walz et al. (2006) generated compound heterozygous mice with a Dp(11)17 allele and a null Rai1 allele, thus resulting in normal disomic gene dosage of Rai1. Normal Rai1 dosage rescued many of the phenotypes observed in heterozygous Dp(11)17 mice, who have 3 copies of the gene, including normalization of body weight and partial normalization of behavior. The phenotype was rescued despite altered trisomic copy number of the other 18 or so genes in the region. Walz et al. (2006) concluded that duplication of Rai1 is responsible for decreased body weight in Dp(11)17 mice and that Rai1 is a dosage-sensitive gene involved in body weight control and complex behavioral responses. </p><p>Girirajan et al. (2008) generated transgenic mice with 4 and 6 copies of the Rai1 gene. The mice showed growth retardation, increased locomotor activity, impaired sensorimotor activity, and abnormal anxiety-related behavior compared to wildtype littermates. Rai1-transgenic mice had an altered gait, decreased forelimb grip strength, and a dominant social behavior. There was a dose-dependent exacerbation of the phenotype, including extreme growth retardation, severe neurologic deficits, and increased hyperactivity in mice with higher Rai1 expression. Girirajan et al. (2008) concluded that Rai1 dosage has major consequences on molecular processes involved in growth, development, and neurologic and behavioral functions, providing evidence for several dosage-thresholds for phenotypic manifestations in humans. </p><p>Burns et al. (2010) investigated the growth and obesity phenotype in a mouse model haploinsufficient for Rai1. Rai1 +/- mice were hyperphagic, had an impaired satiety response, and had an altered abdominal and subcutaneous fat distribution, with Rai1 +/- female mice having a higher proportion of abdominal fat when compared with wildtype female mice. Brain-derived neurotrophic factor (BDNF; 113505), a gene associated with hyperphagia and obesity, was downregulated in the Rai1 +/- mouse hypothalamus, and reporter studies showed that RAI1 directly regulated the expression of BDNF. </p><p>Using quantitative real-time PCR, Williams et al. (2012) found that Rai1 +/- mouse hypothalamus showed dysregulated expression of Clock and other circadian genes during light and dark phases. </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>7 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 SMITH-MAGENIS SYNDROME</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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RAI1, 1-BP DEL, 4929C
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<br />
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ClinVar: RCV000003080
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a person with Smith-Magenis syndrome (182290), Slager et al. (2003) identified deletion on 1 RAI1 allele of a single cytosine in a run of 6 cytosines. The 4929delC on the coding strand produced a frameshift, introducing 74 incorrect amino acids and truncating protein. </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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<h4>
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<span class="mim-font">
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<strong>.0002 SMITH-MAGENIS SYNDROME</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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RAI1, 1-BP DEL, 1308C
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<br />
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ClinVar: RCV000003081
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a person with Smith-Magenis syndrome (182290), Slager et al. (2003) observed deletion of 1 C from a run of 4 Cs ending at nucleotide position 1308 in exon 3 of RAI1. This deletion caused a frameshift that incorporated 34 incorrect amino acids beginning at amino acid position 437, followed by a stop codon and premature termination of the protein. </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 SMITH-MAGENIS SYNDROME</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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RAI1, 29-BP DEL
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<br />
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ClinVar: RCV000003082
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a person with Smith-Magenis syndrome (182290), Slager et al. (2003) found a deletion of 29 basepairs in exon 3 of the RAI gene on 1 allele. This deletion produced a frameshift that introduced 8 incorrect amino acids followed by a stop codon, truncating the protein. </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 SMITH-MAGENIS SYNDROME</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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RAI1, SER1808ASN
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<br />
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SNP: rs104894633,
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gnomAD: rs104894633,
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ClinVar: RCV000003083, RCV002054412
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 17-year-old adopted boy of northern European and Jewish ancestry with features considered consistent with SMS (182290), Girirajan et al. (2005) detected a heterozygous 5423G-A mutation in the RAI1 gene underlying a serine-to-asparagine change at amino acid 1808 (S1808N). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 SMITH-MAGENIS SYNDROME</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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RAI1, GLN1562ARG
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<br />
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SNP: rs104894634,
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ClinVar: RCV000003084
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an 11-year-old white girl with mental retardation, progressive speech delay, stereotypic behavior, intractable complex seizures, and facial dysmorphism consistent with a diagnosis of Smith-Magenis syndrome (182290), Girirajan et al. (2005) described a missense mutation in the RAI1 protein, gln1562 to arg (Q1562R), resulting from a heterozygous adenine-to-guanine transition at nucleotide 4685. </p><p>Using quantitative real-time PCR, Williams et al. (2012) showed that fibroblasts carrying the Q1562R mutation showed dysregulated expression of genes required for circadian rhythmicity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 SMITH-MAGENIS SYNDROME</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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RAI1, 1-BP DEL, 3801C
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<br />
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SNP: rs1598092236,
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ClinVar: RCV000003085
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 14-year-old boy of European descent with features considered consistent with SMS (182290), Girirajan et al. (2005) found a 1-bp deletion in the RAI1 gene, 3801delC, in heterozygous state. The deletion resulted in a frameshift starting at amino acid 1267, leading to misincorporation of 46 amino acids and a downstream stop codon. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SMITH-MAGENIS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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RAI1, 19-BP DEL
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<br />
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ClinVar: RCV000003086
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Girirajan et al. (2005) found that a 19-year-old woman of European descent with features consistent with SMS (182290) had a 19-bp deletion in the RAI1 gene (253del19). </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</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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Bi, W., Ohyama, T., Nakamura, H., Yan, J., Visvanathan, J., Justice, M. J., Lupski, J. R.
|
|
<strong>Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome.</strong>
|
|
Hum. Molec. Genet. 14: 983-995, 2005.
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|
[PubMed: 15746153]
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[Full Text: https://doi.org/10.1093/hmg/ddi085]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Bi, W., Saifi, G. M., Girirajan, S., Shi, X., Szomju, B., Firth, H., Magenis, R. E., Potocki, L., Elsea, S. H., Lupski, J. R.
|
|
<strong>RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome.</strong>
|
|
Am. J. Med. Genet. 140A: 2454-2463, 2006.
|
|
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|
|
[PubMed: 17041942]
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|
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[Full Text: https://doi.org/10.1002/ajmg.a.31510]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bi, W., Saifi, G. M., Shaw, C. J., Walz, K., Fonseca, P., Wilson, M., Potocki, L., Lupski, J. R.
|
|
<strong>Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome.</strong>
|
|
Hum. Genet. 115: 515-524, 2004.
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|
|
[PubMed: 15565467]
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[Full Text: https://doi.org/10.1007/s00439-004-1187-6]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Burns, B., Schmidt, K., Williams, S. R., Kim, S., Girirajan, S., Elsea, S. H.
|
|
<strong>Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome.</strong>
|
|
Hum. Molec. Genet. 19: 4026-4042, 2010.
|
|
|
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|
|
[PubMed: 20663924]
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[Full Text: https://doi.org/10.1093/hmg/ddq317]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Girirajan, S., Elsas, L. J., II, Devriendt, K., Elsea, S. H.
|
|
<strong>RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions.</strong>
|
|
J. Med. Genet. 42: 820-828, 2005.
|
|
|
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|
|
[PubMed: 15788730]
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|
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[Full Text: https://doi.org/10.1136/jmg.2005.031211]
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|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Girirajan, S., Patel, N., Slager, R. E., Tokarz, M. E., Bucan, M., Wiley, J. L., Elsea, S. H.
|
|
<strong>How much is too much? Phenotypic consequences of Rai1 overexpression in mice.</strong>
|
|
Europ. J. Hum. Genet. 16: 941-954, 2008.
|
|
|
|
|
|
[PubMed: 18285828]
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|
|
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|
|
[Full Text: https://doi.org/10.1038/ejhg.2008.21]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Girirajan, S., Vlangos, C. N., Szomju, B. B., Edelman, E., Trevors, C. D., Dupuis, L., Nezarati, M., Bunyan, D. J., Elsea, S. H.
|
|
<strong>Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum.</strong>
|
|
Genet. Med. 8: 417-427, 2006.
|
|
|
|
|
|
[PubMed: 16845274]
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|
|
|
|
|
[Full Text: https://doi.org/10.1097/01.gim.0000228215.32110.89]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hayes, S., Turecki, G., Brisebois, K., Lopes-Cendes, I., Gaspar, C., Riess, O., Ranum, L. P. W., Pulst, S.-M., Rouleau, G. A.
|
|
<strong>CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2).</strong>
|
|
Hum. Molec. Genet. 9: 1753-1758, 2000.
|
|
|
|
|
|
[PubMed: 10915763]
|
|
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|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.12.1753]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Joober, R., Benkelfat, C., Toulouse, A., Lafreniere, R. G. A., Lal, S., Ajroud, S., Turecki, G., Bloom, D., Labelle, A., Lalonde, P., Alda, M., Morgan, K., Palmour, R., Rouleau, G. A.
|
|
<strong>Analysis of 14 CAG repeat-containing genes in schizophrenia.</strong>
|
|
Am. J. Med. Genet. 88: 694-699, 1999.
|
|
|
|
|
|
[PubMed: 10581491]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seranski, P., Heiss, N. S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C. E., Lehrach, H., Poustka, A.
|
|
<strong>Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes.</strong>
|
|
Genomics 56: 1-11, 1999.
|
|
|
|
|
|
[PubMed: 10036180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1998.5647]
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seranski, P., Hoff, C., Radelof, U., Hennig, S., Reinhardt, R., Schwartz, C. E., Heiss, N. S., Poustka, A.
|
|
<strong>RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients.</strong>
|
|
Gene 270: 69-76, 2001.
|
|
|
|
|
|
[PubMed: 11404004]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(01)00415-2]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., Elsea, S. H.
|
|
<strong>Mutations in RAI1 associated with Smith-Magenis syndrome.</strong>
|
|
Nature Genet. 33: 466-468, 2003.
|
|
|
|
|
|
[PubMed: 12652298]
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|
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|
|
[Full Text: https://doi.org/10.1038/ng1126]
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G. A.
|
|
<strong>Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia.</strong>
|
|
Genomics 82: 162-171, 2003.
|
|
|
|
|
|
[PubMed: 12837267]
|
|
|
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|
|
[Full Text: https://doi.org/10.1016/s0888-7543(03)00101-0]
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Walz, K., Caratini-Rivera, S., Bi, W., Fonseca, P., Mansouri, D. L., Lynch, J., Vogel, H., Noebels, J. L., Bradley, A., Lupski, J. R.
|
|
<strong>Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance.</strong>
|
|
Molec. Cell. Biol. 23: 3646-3655, 2003.
|
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|
|
|
|
[PubMed: 12724422]
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|
|
[Full Text: https://doi.org/10.1128/MCB.23.10.3646-3655.2003]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Walz, K., Paylor, R., Yan, J., Bi, W., Lupski, J. R.
|
|
<strong>Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2).</strong>
|
|
J. Clin. Invest. 116: 3035-3041, 2006.
|
|
|
|
|
|
[PubMed: 17024248]
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|
|
[Full Text: https://doi.org/10.1172/JCI28953]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Walz, K., Spencer, C., Kaasik, K., Lee, C. C., Lupski, J. R., Paylor, R.
|
|
<strong>Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).</strong>
|
|
Hum. Molec. Genet. 13: 367-378, 2004.
|
|
|
|
|
|
[PubMed: 14709593]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddh044]
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., Elsea, S. H.
|
|
<strong>Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.</strong>
|
|
Am. J. Hum. Genet. 90: 941-949, 2012.
|
|
|
|
|
|
[PubMed: 22578325]
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|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.04.013]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Yan, J., Keener, V. W., Bi, W., Walz, K., Bradley, A., Justice, M. J., Lupski, J. R.
|
|
<strong>Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome.</strong>
|
|
Hum. Molec. Genet. 13: 2613-2624, 2004.
|
|
|
|
|
|
[PubMed: 15459175]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddh288]
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</p>
|
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</li>
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</ol>
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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|
</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
George E. Tiller - updated : 06/21/2017<br>Patricia A. Hartz - updated : 7/26/2012<br>Ada Hamosh - updated : 10/12/2010<br>Cassandra L. Kniffin - updated : 8/19/2008<br>George E. Tiller - updated : 2/7/2008<br>Ada Hamosh - updated : 7/25/2007<br>George E. Tiller - updated : 6/13/2007<br>Marla J. F. O'Neill - updated : 2/2/2007<br>Cassandra L. Kniffin - updated : 12/8/2006<br>Victor A. McKusick - updated : 6/22/2006<br>Victor A. McKusick - updated : 4/27/2005<br>Patricia A. Hartz - updated : 7/22/2003<br>Victor A. McKusick - updated : 3/21/2003
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz : 3/20/2003
|
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