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Entry
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- *308380 - INTERLEUKIN 2 RECEPTOR, GAMMA; IL2RG
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- OMIM
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<p>
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<span class="h4">*308380</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<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="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</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/308380">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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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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<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 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 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="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=ENSG00000147168;t=ENST00000374202" 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=3561" 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=308380" 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 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="small">
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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=ENSG00000147168;t=ENST00000374202" 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_000206,XM_047442089" 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_000206" 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=308380" 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=02391&isoform_id=02391_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/IL2RG" 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/219890,307058,349632,400048,1480072,4557882,15929028,50897470,58736951,58736953,58736955,58736957,58736959,119625724,189067456,221042324,224763150,224765638,859808024,2217392066,2462629360" 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/P31785" 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=3561" 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=ENSG00000147168;t=ENST00000374202" 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=IL2RG" 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=IL2RG" 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+3561" 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/IL2RG" 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:3561" 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/3561" 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=chrX&hgg_gene=ENST00000646505.1&hgg_start=71107404&hgg_end=71111577&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6010" 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/il2rg" 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=308380[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=308380[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000147168" 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=IL2RG" 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=IL2RG" 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=IL2RG" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://research.nhgri.nih.gov/apps/scid/IL2RGbase.shtml" title="X-Linked Severe Combined Immuno deficiency SCID" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">X-Linked Severe Combined I…</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/IL2RG" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">X-chromosome gene database</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=IL2RG" title="CCHMC Molecular Genetics Laboratory Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC Molecular Genetics L…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=IL2RG&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/PA196" 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:6010" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96551" 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/IL2RG#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:96551" 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/3561/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/results?search_type=advanced&omia_id=000899,002763" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3561" 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-080402-1" 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:308380" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3561" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=IL2RG&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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308380
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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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INTERLEUKIN 2 RECEPTOR, GAMMA; IL2RG
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
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INTERLEUKIN RECEPTOR, COMMON GAMMA CHAIN<br />
|
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INTERLEUKIN RECEPTOR, GAMMA-C<br />
|
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CD132 ANTIGEN; CD132
|
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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=IL2RG" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">IL2RG</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/X/403?start=-3&limit=10&highlight=403">Xq13.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:71107404-71111577&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'})">X:71,107,404-71,111,577</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>
|
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<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">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=312863,300400" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
|
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</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
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>
|
|
|
|
<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/403?start=-3&limit=10&highlight=403">
|
|
Xq13.1
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Combined immunodeficiency, X-linked, moderate
|
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|
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</span>
|
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</td>
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PheneGene Graphics <span class="caret"></span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>Cytokines are potent, soluble mediators that regulate homeostasis of the immune system. IL2RG is known as the interleukin receptor common gamma chain, or gamma-c, because it heterodimerizes with at least 6 unique cytokine-specific interleukin receptor alpha chains, IL2RA (<a href="/entry/147730">147730</a>), IL4RA (<a href="/entry/147781">147781</a>), IL7RA (<a href="/entry/146661">146661</a>), IL9RA (<a href="/entry/300007">300007</a>), IL15RA (<a href="/entry/601070">601070</a>), and IL21RA (<a href="/entry/605383">605383</a>), to form distinct receptor complexes for the cytokines IL2 (<a href="/entry/147680">147680</a>), IL4 (<a href="/entry/147780">147780</a>), IL7 (<a href="/entry/146660">146660</a>), IL9 (<a href="/entry/146931">146931</a>), IL15 (<a href="/entry/600554">600554</a>), and IL21 (<a href="/entry/605384">605384</a>), respectively. The IL2 and IL21 receptor complexes are heterotrimers that also include a shared beta chain, IL2RB/IL15RB (<a href="/entry/146710">146710</a>) (<a href="#2" class="mim-tip-reference" title="Brandt, K., Singh, P. B., Bulfone-Paus, S., Ruckert, R. <strong>Interleukin-21: a new modulator of immunity, infection, and cancer.</strong> Cytokine Growth Factor Rev. 18: 223-232, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17509926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17509926</a>] [<a href="https://doi.org/10.1016/j.cytogfr.2007.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17509926">Brandt et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17509926" 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>IL2 affects the growth and differentiation of T cells, B cells, natural killer cells, glioma cells, and cells of the monocyte lineage after specifically interacting with its receptors. The IL2 receptor (IL2R) consists of 2 subunits, alpha (IL2RA) and beta (IL2RB). <a href="#29" class="mim-tip-reference" title="Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Munakata, H., Nakamura, M., Sugamura, K. <strong>Cloning of the gamma chain of the human IL-2 receptor.</strong> Science 257: 379-382, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631559</a>] [<a href="https://doi.org/10.1126/science.1631559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631559">Takeshita et al. (1992)</a> identified a third IL2R subunit, the gamma chain, and isolated the corresponding cDNA from a human T-cell line. The deduced 369-amino acid protein has a molecular mass of 39.9 kD and shows sequence similarity to members of the cytokine receptor family. Northern blot analysis detected a dominant 1.8-kb mRNA transcript in human T and B cells; a second 3.6-kb mRNA transcript was also detected. No IL2RG mRNA transcripts were detected in human nonlymphoid cells, such as promonocytes, epithelial cells, or hepatocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631559" 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="Noguchi, M., Adelstein, S., Cao, X., Leonard, W. J. <strong>Characterization of the human interleukin-2 receptor gamma chain gene.</strong> J. Biol. Chem. 268: 13601-13608, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8514792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8514792</a>]" pmid="8514792">Noguchi et al. (1993)</a> found that the IL2RG protein, like the IL2RB protein, contains 2 pairs of conserved cysteines typical of cytokine receptor superfamily proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8514792" 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="#16" class="mim-tip-reference" title="Noguchi, M., Adelstein, S., Cao, X., Leonard, W. J. <strong>Characterization of the human interleukin-2 receptor gamma chain gene.</strong> J. Biol. Chem. 268: 13601-13608, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8514792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8514792</a>]" pmid="8514792">Noguchi et al. (1993)</a> determined that the IL2RG gene contains 8 exons and spans approximately 4.2 kb. Southern blot analysis suggested that the gene is present in single copy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8514792" 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="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> sequenced the IL2RG gene and elucidated its genomic organization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" 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 study of somatic cell hybrids, <a href="#18" class="mim-tip-reference" title="Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., Leonard, W. J. <strong>Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.</strong> Cell 73: 147-157, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8462096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8462096</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90167-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8462096">Noguchi et al. (1993)</a> and <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> independently mapped the IL2RG gene to chromosome Xq13. Relationships to markers in linkage studies suggested that IL2RG and XSCID, the locus for X-linked severe combined immunodeficiency (<a href="/entry/300400">300400</a>), had the same location. By fluorescence in situ hybridization and PCR amplification of somatic cell hybrid DNAs, <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> mapped IL2RG to Xq13.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8401490+8462096" 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="Cao, X., Kozak, C. A., Liu, Y.-J., Noguchi, M., O'Connell, E., Leonard, W. J. <strong>Characterization of cDNAs encoding the murine interleukin 2 receptor (IL-2R) gamma chain: chromosomal mapping and tissue specificity of IL-2R gamma chain expression.</strong> Proc. Nat. Acad. Sci. 90: 8464-8468, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8378320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8378320</a>] [<a href="https://doi.org/10.1073/pnas.90.18.8464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8378320">Cao et al. (1993)</a> localized the murine Il2rg gene to the X chromosome between Rsvp and Plp and demonstrated that a defect in the gene is not responsible for the X-linked xid mutation, which maps to the same region; see <a href="/entry/300300">300300</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8378320" 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>Functional expression studies by <a href="#29" class="mim-tip-reference" title="Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Munakata, H., Nakamura, M., Sugamura, K. <strong>Cloning of the gamma chain of the human IL-2 receptor.</strong> Science 257: 379-382, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631559</a>] [<a href="https://doi.org/10.1126/science.1631559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631559">Takeshita et al. (1992)</a> showed that the IL2 receptor gamma chain was necessary for formation of high- and intermediate-affinity IL2 receptors, which consist of alpha-beta-gamma heterotrimers and beta-gamma heterodimers, respectively. <a href="#29" class="mim-tip-reference" title="Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Munakata, H., Nakamura, M., Sugamura, K. <strong>Cloning of the gamma chain of the human IL-2 receptor.</strong> Science 257: 379-382, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631559</a>] [<a href="https://doi.org/10.1126/science.1631559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631559">Takeshita et al. (1992)</a> concluded that the gamma chain is an indispensable component of the functional IL2 receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The gamma subunit of the IL2 receptor is a subunit also of the IL4 receptor and of the IL7 receptor, i.e., it is a shared or common component of at least 3 cytokine receptors. The designation 'common gamma chain' (gamma-c) was proposed (<a href="#12" class="mim-tip-reference" title="Kondo, M., Takeshita, T., Ishii, N., Nakamura, M., Watanabe, S., Arai, K., Sugamura, K. <strong>Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4.</strong> Science 262: 1874-1877, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8266076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8266076</a>] [<a href="https://doi.org/10.1126/science.8266076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8266076">Kondo et al., 1993</a>; <a href="#17" class="mim-tip-reference" title="Noguchi, M., Nakamura, Y., Russell, S. M., Ziegler, S. F., Tsang, M., Cao, X., Leonard, W. J. <strong>Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor.</strong> Science 262: 1877-1880, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8266077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8266077</a>] [<a href="https://doi.org/10.1126/science.8266077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8266077">Noguchi et al., 1993</a>; <a href="#22" class="mim-tip-reference" title="Russell, S. M., Keegan, A. D., Harada, N., Nakamura, Y., Noguchi, M., Leland, P., Friedmann, M. C., Miyajima, A., Puri, R. K., Paul, W. E., Leonard, W. J. <strong>Interleukin-2 receptor gamma-chain: a functional component of the interleukin-4 receptor.</strong> Science 262: 1880-1883, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8266078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8266078</a>] [<a href="https://doi.org/10.1126/science.8266078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8266078">Russell et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8266076+8266078+8266077" 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="#22" class="mim-tip-reference" title="Russell, S. M., Keegan, A. D., Harada, N., Nakamura, Y., Noguchi, M., Leland, P., Friedmann, M. C., Miyajima, A., Puri, R. K., Paul, W. E., Leonard, W. J. <strong>Interleukin-2 receptor gamma-chain: a functional component of the interleukin-4 receptor.</strong> Science 262: 1880-1883, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8266078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8266078</a>] [<a href="https://doi.org/10.1126/science.8266078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8266078">Russell et al. (1993)</a> suggested that the gamma-c subunit may be shared with the interleukin-9 receptor. The sharing of the gamma subunit by several receptors explained why humans and mice that lack IL2 entirely show milder symptoms than those with IL2RG deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8266078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Sharfe, N., Shahar, M., Roifman, C. M. <strong>An interleukin-2 receptor gamma chain mutation with normal thymus morphology.</strong> J. Clin. Invest. 100: 3036-3043, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9399950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9399950</a>] [<a href="https://doi.org/10.1172/JCI119858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9399950">Sharfe et al. (1997)</a> stated that the gamma-c chain is shared by 5 interleukin receptor complexes: IL2, IL4, IL7, IL9, and IL15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9399950" 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="Asao, H., Okuyama, C., Kumaki, S., Ishii, N., Tsuchiya, S., Foster, D., Sugamura, K. <strong>Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex.</strong> J. Immun. 167: 1-5, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11418623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11418623</a>] [<a href="https://doi.org/10.4049/jimmunol.167.1.1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11418623">Asao et al. (2001)</a> showed that IL21 binds to IL21R in IL2RG-deficient cell lines, but fails to transduce signals. In cell lines expressing IL2RG, binding and activation of JAK1 (<a href="/entry/147795">147795</a>), JAK3 (<a href="/entry/600173">600173</a>), STAT1 (<a href="/entry/600555">600555</a>), and STAT3 (<a href="/entry/102582">102582</a>) occurs, indicating that IL2RG is an indispensable subunit of the functional IL21R complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11418623" 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="Lamaze, C., Dujeancourt, A., Baba, T., Lo, C. G., Benmerah, A., Dautry-Varsat, A. <strong>Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway.</strong> Molec. Cell 7: 661-671, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11463390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11463390</a>] [<a href="https://doi.org/10.1016/s1097-2765(01)00212-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11463390">Lamaze et al. (2001)</a> selectively blocked clathrin (see <a href="/entry/118960">118960</a>)-dependent endocytosis using dominant-negative mutants of EPS15 (<a href="/entry/600051">600051</a>) and showed that clathrin-mediated endocytosis of transferrin (<a href="/entry/190000">190000</a>) was inhibited, while endocytosis of the IL2Rs proceeded normally. Ultrastructural and biochemical experiments showed that clathrin-independent endocytosis of IL2Rs existed constitutively in lymphocytes and was coupled to their association with detergent-resistant membrane domains. Clathrin-independent endocytosis required dynamin (see <a href="/entry/602377">602377</a>) and was specifically regulated by Rho family GTPases (see <a href="/entry/604980">604980</a>). These results defined novel properties of receptor-mediated endocytosis and established that IL2R is efficiently internalized through this clathrin-independent pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11463390" 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 flow cytometry, <a href="#7" class="mim-tip-reference" title="Corrigall, V. M., Arastu, M., Khan, S., Shah, C., Fife, M., Smeets, T., Tak, P.-P., Panayi, G. S. <strong>Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production.</strong> J. Immun. 166: 4141-4147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11238664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11238664</a>] [<a href="https://doi.org/10.4049/jimmunol.166.6.4141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11238664">Corrigall et al. (2001)</a> detected expression of a functional IL2R of intermediate affinity composed solely of IL2RB and IL2RG on fibroblast-like synoviocytes (FLS) obtained from rheumatoid arthritis and osteoarthritis patients. Addition of recombinant IL2, IL1B (<a href="/entry/147720">147720</a>), or TNFA (<a href="/entry/191160">191160</a>) independently did not upregulate expression of the receptors on FLS, but IL2 or IL1B significantly increased expression of intracellular tyrosine-phosphorylated proteins and the production of MCP1 (<a href="/entry/158105">158105</a>). <a href="#7" class="mim-tip-reference" title="Corrigall, V. M., Arastu, M., Khan, S., Shah, C., Fife, M., Smeets, T., Tak, P.-P., Panayi, G. S. <strong>Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production.</strong> J. Immun. 166: 4141-4147, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11238664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11238664</a>] [<a href="https://doi.org/10.4049/jimmunol.166.6.4141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11238664">Corrigall et al. (2001)</a> proposed that MCP1 in the synovial membrane serves to recruit macrophages and perpetuate inflammation in the joints of patients with rheumatoid arthritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11238664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#30" class="mim-tip-reference" title="Wang, X., Rickert, M., Garcia, K. C. <strong>Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gamma-c receptors.</strong> Science 310: 1159-1163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293754</a>] [<a href="https://doi.org/10.1126/science.1117893" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16293754">Wang et al. (2005)</a> reported the crystal structure of the quaternary complex of IL2 with IL2RA, IL2RB, and IL2RG at a resolution of 2.3 angstroms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="LaPorte, S. L., Juo, Z. S., Vaclavikova, J., Colf, L. A., Qi, X., Heller, N. M., Keegan, A. D., Garcia, K. C. <strong>Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.</strong> Cell 132: 259-272, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18243101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18243101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18243101[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.cell.2007.12.030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18243101">LaPorte et al. (2008)</a> reported the crystal structures of the complete set of IL4 and IL13 (<a href="/entry/147683">147683</a>) type I (IL4RA/IL2RG/IL4) and type II (IL4RA/IL13RA1/IL4 and IL4RA/IL13RA1/IL13) ternary signaling complexes at the 3.0-angstrom level. They noted that the type I receptor complex is more active in regulating Th2 development, whereas the type II receptor complex is not found on T cells and is more active in regulating cells that mediate airway hypersensitivity and mucus secretion. The type I complex revealed a structural basis for the ability of IL2RG to recognize 6 different IL2RG cytokines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18243101" 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 3 unrelated patients with X-linked severe combined immunodeficiency (<a href="/entry/300400">300400</a>), <a href="#18" class="mim-tip-reference" title="Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., Leonard, W. J. <strong>Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.</strong> Cell 73: 147-157, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8462096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8462096</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90167-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8462096">Noguchi et al. (1993)</a> identified 3 different mutations in the IL2RG gene (<a href="#0001">308380.0001</a>-<a href="#0003">308380.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8462096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 unrelated affected males with SCID <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> identified unique mutations in the IL2RG gene (<a href="#0004">308380.0004</a>-<a href="#0007">308380.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" 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="#19" class="mim-tip-reference" title="Pepper, A. E., Buckley, R. H., Small, T. N., Puck, J. M. <strong>Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.</strong> Am. J. Hum. Genet. 57: 564-571, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668284</a>]" pmid="7668284">Pepper et al. (1995)</a> found that of 40 IL2RG mutations found in unrelated SCID males, 6 were point mutations at the CpG dinucleotide at cDNA residues 690-691 encoding amino acid arg226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA residue 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL2 receptor complex. <a href="#19" class="mim-tip-reference" title="Pepper, A. E., Buckley, R. H., Small, T. N., Puck, J. M. <strong>Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.</strong> Am. J. Hum. Genet. 57: 564-571, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668284</a>]" pmid="7668284">Pepper et al. (1995)</a> stated that mutations at these 2 hotspots constituted more than 20% of all XSCID mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668284" 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="#15" class="mim-tip-reference" title="Leonard, W. J. <strong>The molecular basis of X-linked severe combined immunodeficiency: defective cytokine receptor signaling.</strong> Annu. Rev. Med. 47: 229-239, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8712778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8712778</a>] [<a href="https://doi.org/10.1146/annurev.med.47.1.229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8712778">Leonard (1996)</a> provided a review of the molecular basis of X-linked SCID with a listing of the mutations identified in the IL2RG gene. <a href="#9" class="mim-tip-reference" title="Fugmann, S. D., Muller, S., Friedrich, W., Bartram, C. R., Schwarz, K. <strong>Mutations in the gene for the common gamma chain (gamma-c) in X-linked severe combined immunodeficiency.</strong> Hum. Genet. 103: 730-731, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921912</a>] [<a href="https://doi.org/10.1007/pl00008710" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921912">Fugmann et al. (1998)</a> studied the IL2RG gene in 31 patients with SCID. Among 11 patients with XSCID, 10 different mutations were identified in the IL2RG gene, including 8 novel mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9921912+8712778" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with X-linked combined immunodeficiency (<a href="/entry/312863">312863</a>), <a href="#24" class="mim-tip-reference" title="Sharfe, N., Shahar, M., Roifman, C. M. <strong>An interleukin-2 receptor gamma chain mutation with normal thymus morphology.</strong> J. Clin. Invest. 100: 3036-3043, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9399950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9399950</a>] [<a href="https://doi.org/10.1172/JCI119858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9399950">Sharfe et al. (1997)</a> identified a mutation in the IL2RG gene (<a href="#0012">308380.0012</a>), which resulted in a protein that was sufficiently stable to be expressed at the cell surface. Although clinically immunodeficient, the patient had normal numbers of peripheral T and B cells, responded normally to mitogenic stimuli, and had a normal thymus gland. While the T-cell receptor repertoire appeared complete, suggesting normal T-cell differentiation, the patient's T cells demonstrated a reduced ability to bind IL2, resulting in immunodeficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9399950" 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="Cacalano, N. A., Johnston, J. A. <strong>Interleukin-2 signaling and inherited immunodeficiency.</strong> Am. J. Hum. Genet. 65: 287-293, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417270</a>] [<a href="https://doi.org/10.1086/302518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417270">Cacalano and Johnston (1999)</a> reviewed IL2 signaling in relation to inherited immunodeficiency. Formal genetic proof that the IL2R components are critical for T-cell development came with the identification of patients lacking either IL2RG or JAK3 (<a href="/entry/600173">600173</a>). These patients presented with phenotypically identical T-negative/B-positive/NK-negative SCID, inherited as an X-linked recessive or an autosomal recessive (<a href="/entry/600802">600802</a>) disorder, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Yu, X., Almeida, J., Darko, S., van der Burg, M., DeRavin, S. S., Malech, H., Gennery, A., Chinn, I., Markert, M. L., Douek, D. C., Milner, J. D. <strong>Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development.</strong> J. Allergy Clin. Immun. 133: 1109-1115, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24406074</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24406074[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.jaci.2013.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24406074">Yu et al. (2014)</a> performed deep sequencing on complementarity-determining region-3 (CDR3) of T-cell receptor (TCR)-beta (see <a href="/entry/186930">186930</a>) in CD4 (<a href="/entry/186940">186940</a>)-positive and CD8 (see <a href="/entry/186910">186910</a>)-positive T cells from 2 patients with RAG1 (<a href="/entry/179615">179615</a>) or IL2RG mutations and autoimmunity and/or granulomatous disease, but not severe immunodeficiency (see <a href="/entry/233650">233650</a> for information on the RAG1-associated phenotype); 5 patients with Omenn syndrome (<a href="/entry/603554">603554</a>) caused by RAG1 or RAG2 (<a href="/entry/179616">179616</a>) mutations; 2 patients with Omenn syndrome-like phenotypes caused by a ZAP70 (<a href="/entry/176947">176947</a>) mutation (see <a href="/entry/269840">269840</a>) or by atypical DiGeorge syndrome (<a href="/entry/188400">188400</a>); and 4 healthy controls. They found that patients with Omenn syndrome due to RAG1 or RAG2 mutations had poor TCR-beta diversity compared with controls and patients with Omenn syndrome not due to RAG1 or RAG2 mutations. The 2 patients with RAG1 or IL2RG mutations associated with autoimmunity and granulomatous disease did not have diminished diversity, but instead had skewed V-J pairing and CDR3 amino acid use. <a href="#31" class="mim-tip-reference" title="Yu, X., Almeida, J., Darko, S., van der Burg, M., DeRavin, S. S., Malech, H., Gennery, A., Chinn, I., Markert, M. L., Douek, D. C., Milner, J. D. <strong>Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development.</strong> J. Allergy Clin. Immun. 133: 1109-1115, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24406074</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24406074[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.jaci.2013.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24406074">Yu et al. (2014)</a> concluded that RAG enzymatic function may be necessary for normal CDR3 junctional diversity and that aberrant TCR generation, but not numeric diversity, may contribute to immune dysregulation in patients with hypomorphic forms of SCID. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24406074" 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=308380[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 patient with X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#18" class="mim-tip-reference" title="Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., Leonard, W. J. <strong>Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.</strong> Cell 73: 147-157, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8462096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8462096</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90167-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8462096">Noguchi et al. (1993)</a> identified a C-to-T transition in exon 7 of the IL2RG gene, resulting in an arg267-to-ter (R267X) substitution and truncation of 81 amino acids of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8462096" 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 patient with X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#18" class="mim-tip-reference" title="Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., Leonard, W. J. <strong>Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.</strong> Cell 73: 147-157, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8462096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8462096</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90167-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8462096">Noguchi et al. (1993)</a> identified a C-to-A transversion in exon 7 of the IL2RG gene, resulting in a ser286-to-ter (S286X) substitution and the truncation of 62 amino acids of the protein. This patient became known as Bubble Boy David because he lived in an isolation bubble in Houston for a long time and his disease became known as Bubble Boy disease. His early clinical course and immune function were reported by <a href="#26" class="mim-tip-reference" title="South, M. A., Montgomery, J. R., Richie, E., Mukhopadhyay, N., Criswell, B. S., Mackler, B. F., De Fazio, S. R., Bealmear, P., Heim, L. R., Trentin, J. J., Dressman, G. R., O'Neill, P. <strong>Four-year study of a boy with combined immune deficiency maintained in strict reverse isolation from birth. IV. Immunologic studies.</strong> Pediat. Res. 11: 71-78, 1977."None>South et al. (1977)</a> and <a href="#25" class="mim-tip-reference" title="Shearer, W. T., Ritz, J., Finegold, M. J., Guerra, I. C., Rosenblatt, H. H., Lewis, D. E., Pollack, M. S., Taber, L. H., Suyama, C. V., Grumet, F. C., Cleary, M. L., Warnke, R., Sklar, J. <strong>Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency.</strong> New Eng. J. Med. 312: 1151-1159, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2984567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2984567</a>] [<a href="https://doi.org/10.1056/NEJM198505023121804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2984567">Shearer et al. (1985)</a>. A male sib was also affected. His immunodeficiency was characterized by panhypogammaglobulinemia, lymphopenia with diminished T cells (varying from 10 to 40% over 12 years), elevated B cells, and essentially absent proliferation to mitogens or antigens. Following T-depleted haploidentical bone marrow transplantation from his sister, there was no improvement in immune function. He died 124 days posttransplant from an EBV-associated lymphoproliferative syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2984567+8462096" 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">rs111033619 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033619;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=rs111033619" 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=rs111033619" 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=RCV000010702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010702</a>
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<p>In a patient with X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> identified a 200T-A transversion in exon 2 of the IL2RG gene, resulting in a cys62-to-ter (C62X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" 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 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
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IL2RG, GLY114ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033620 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033620;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=rs111033620" 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=rs111033620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010703" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010703" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010703</a>
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<p>In a patient with X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> identified a 355G-A transition in exon 3 of the IL2RG gene, resulting in a gly114-to-asp (G114D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" 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="0006" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0006 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
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IL2RG, IVS3DS, G-A, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569480018 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569480018;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=rs1569480018" 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=rs1569480018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010704" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010704" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010704</a>
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</span>
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<p>In a boy with X-linked SCID (<a href="/entry/300400">300400</a>) and no detectable IL2RG mRNA, <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> identified a G-to-A transition in the first position of the splice donor site of intron 3 of the IL2RG gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" 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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<h4>
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<span class="mim-font">
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<strong>.0007 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
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IL2RG, ILE153ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033621 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033621;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=rs111033621" 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=rs111033621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010705" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010705" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010705</a>
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<span class="mim-text-font">
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<p>In a boy with X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#20" class="mim-tip-reference" title="Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S. <strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong> Hum. Molec. Genet. 2: 1099-1104, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401490</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401490">Puck et al. (1993)</a> identified a 472T-A transversion in exon 4 of the IL2RG gene, resulting in an ile153-to-asn (I153N) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<strong>.0008 COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
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IL2RG, LEU271GLN
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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> rs137852510 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852510;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/rs137852510?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=rs137852510" 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=rs137852510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010706 OR RCV001038281" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010706, RCV001038281" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010706...</a>
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</span>
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<p>In 3 affected males with X-linked combined immunodeficiency (XCID; <a href="/entry/312863">312863</a>), which is phenotypically milder than X-linked severe combined immunodeficiency (<a href="/entry/300400">300400</a>), <a href="#23" class="mim-tip-reference" title="Schmalstieg, F. C., Leonard, W. J., Noguchi, M., Berg, M., Rudloff, H. E., Denney, R. M., Dave, S. K., Brooks, E. G., Goldman, A. S. <strong>Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.</strong> J. Clin. Invest. 95: 1169-1173, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7883965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7883965</a>] [<a href="https://doi.org/10.1172/JCI117765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7883965">Schmalstieg et al. (1995)</a> identified a leu271-to-gln (L271Q) substitution in exon 7 of the IL2RG gene. A normal brother did not have the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7883965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
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IL2RG, 9-BP DUP, GLN-HIS-TRP INS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776729 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776729;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=rs587776729" 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=rs587776729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010707</a>
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<span class="mim-text-font">
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<p>By genetic linkage studies in a large Canadian pedigree with XSCID (<a href="/entry/300400">300400</a>), <a href="#21" class="mim-tip-reference" title="Puck, J. M., Pepper, A. E., Bedard, P.-M., Laframboise, R. <strong>Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency.</strong> J. Clin. Invest. 95: 895-899, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7860773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7860773</a>] [<a href="https://doi.org/10.1172/JCI117740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7860773">Puck et al. (1995)</a> found the source of the mutation in the proband's grandmother. Despite her having 1 affected son and 2 carrier daughters with skewed X inactivation, her T cells did not show the expected skewed inactivation. Single-strand conformation polymorphism analysis of IL2RG in the affected proband demonstrated an abnormality in exon 5; sequencing demonstrated a 9-nucleotide in-frame duplication-insertion resulting in a duplication of 3 extracellular amino acids (glutamine, histidine, and tryptophan) just adjacent to and including the first tryptophan of the WSXWS motif found in all members of the cytokine receptor gene superfamily. The 3 additional amino acids were inserted just before residue 235. Mutation detection in the pedigree confirmed that the founder grandmother's somatic cells had only normal IL2RG, and that the SCID-associated X-chromosome haplotype was inherited by 3 daughters, 1 with a wildtype IL2RG gene and 2 others with the insertional mutation. The findings indicated that the grandmother had germline mosaicism, an unusual finding in females. This X-linked SCID family emphasized the limitations of genetic diagnosis by linkage as compared with direct mutation analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7860773" 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">rs111033622 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033622;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=rs111033622" 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=rs111033622" 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=RCV000010708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010708</a>
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<p>In a male infant in whom XSCID (<a href="/entry/300400">300400</a>) was suspected at 1 year of age, <a href="#28" class="mim-tip-reference" title="Stephan, V., Wahn, V., Le Deist, F., Dirksen, U., Broker, B., Muller-Fleckenstein, I., Horneff, G., Schroten, H., Fischer, A., de Saint Basile, G. <strong>Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells.</strong> New Eng. J. Med. 335: 1563-1567, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900089</a>] [<a href="https://doi.org/10.1056/NEJM199611213352104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900089">Stephan et al. (1996)</a> identified a 343T-C transition in exon 3 of the IL2RG gene, resulting in a cys115-to-arg (C115R) substitution. The patient's mother was heterozygous for the mutation. A maternal uncle and a maternal granduncle had died of pneumonia at ages 4 months and 6 months, respectively. The affected child had BCG vaccination at the age of 2 weeks. At 6 months of age, he was hospitalized for severe interstitial pneumonia. Physical examination at 1 year of age showed no signs of graft-versus-host disease (GVHD; see <a href="/entry/614395">614395</a>) and no abnormalities except for a large abscess in the left lumbar region from which acid-fast bacilli with genetic characteristics of the Calmette-Guerin bacillus were identified. Immunologic investigations showed a normal number of T cells, a high B-cell count, and hypogammaglobulinemia with no detectable specific antibody responses. The skin test for purified protein derivative was positive and there were at least attenuated proliferative responses to antigens and mitogens. These unusual findings led to genetic analysis which showed that the gamma chain of IL2R was not expressed in the patient's B cells. Because of the unexpected presence of circulating mature T cells, <a href="#28" class="mim-tip-reference" title="Stephan, V., Wahn, V., Le Deist, F., Dirksen, U., Broker, B., Muller-Fleckenstein, I., Horneff, G., Schroten, H., Fischer, A., de Saint Basile, G. <strong>Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells.</strong> New Eng. J. Med. 335: 1563-1567, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900089</a>] [<a href="https://doi.org/10.1056/NEJM199611213352104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900089">Stephan et al. (1996)</a> sorted and analyzed the patient's CD3+ T cells for expression of the gamma-c chain. Surprisingly, expression of this chain by T cells with either the CD4+ or CD8+ phenotype was normal, and sequencing of the IL2RG gene revealed the wildtype sequence at position 343. In contrast, the sorted CD19+ B cells, the sorted CD14+ monocytes, and the polymorphonuclear-cell population had no detectable expression of the gamma-c chain on their surface and contained the C115R mutation. The possibility that the patient's circulating T-cell population was derived from the engraftment of T cells in the mother in utero was excluded by T-cell karyotyping and HLA typing. In addition, the X chromosome present in the patient's T-cell and B-cell populations was assessed by study of 2 microsatellites flanking the IL2RG locus. These cell populations had only 1 X chromosome derived from the mother with the same X chromosome present in both T-cell and B-cell populations. <a href="#28" class="mim-tip-reference" title="Stephan, V., Wahn, V., Le Deist, F., Dirksen, U., Broker, B., Muller-Fleckenstein, I., Horneff, G., Schroten, H., Fischer, A., de Saint Basile, G. <strong>Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells.</strong> New Eng. J. Med. 335: 1563-1567, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900089</a>] [<a href="https://doi.org/10.1056/NEJM199611213352104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900089">Stephan et al. (1996)</a> suggested that a single reversion event had occurred in a T-cell progenitor that gave rise to a number of diversified T-cell clones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900089" 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> rs111033617 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033617;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/rs111033617?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=rs111033617" 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=rs111033617" 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=RCV000010709 OR RCV003231098" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010709, RCV003231098" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010709...</a>
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<p>In a patient with T-, B+ X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#6" class="mim-tip-reference" title="Clark, P. A., Lester, T., Genet, S., Jones, A. M., Hendriks, R., Levinsky, R. J., Kinnon, C. <strong>Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R-gamma chain gene by single-strand conformation polymorphism analysis.</strong> Hum. Genet. 96: 427-432, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557965</a>] [<a href="https://doi.org/10.1007/BF00191801" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7557965">Clark et al. (1995)</a> identified a 2943G-A transition in the IL2RG gene, resulting in an arg285-to-gln (R285Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7557965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Jones, A. M., Clark, P. A., Katz, F., Genet, S., McMahon, C., Alterman, L., Cant, A., Kinnon, C. <strong>B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation.</strong> Hum. Genet. 99: 677-680, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150740</a>] [<a href="https://doi.org/10.1007/s004390050428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9150740">Jones et al. (1997)</a> noted that X-linked SCID is characterized by the absence, or very low numbers, of T cells, with normal or even high numbers of B cells. However, in a boy with SCID who had very low numbers of both B cells and T cells, <a href="#11" class="mim-tip-reference" title="Jones, A. M., Clark, P. A., Katz, F., Genet, S., McMahon, C., Alterman, L., Cant, A., Kinnon, C. <strong>B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation.</strong> Hum. Genet. 99: 677-680, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150740</a>] [<a href="https://doi.org/10.1007/s004390050428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9150740">Jones et al. (1997)</a> identified the R285Q mutation. The patient's mother and a maternal aunt were both found to have unilateral X inactivation in their T cells. <a href="#11" class="mim-tip-reference" title="Jones, A. M., Clark, P. A., Katz, F., Genet, S., McMahon, C., Alterman, L., Cant, A., Kinnon, C. <strong>B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation.</strong> Hum. Genet. 99: 677-680, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150740</a>] [<a href="https://doi.org/10.1007/s004390050428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9150740">Jones et al. (1997)</a> stated that in about one-third of the cases of typical SCIDX1, there is no previous family history. In these families, the suspicion of SCIDX1 is raised by the phenotype and may be confirmed by X inactivation in T cells and/or by mutation analysis. The authors cautioned that the unexpected finding of low B cells may mistakenly suggest an autosomal form of SCID. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150740" 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">rs111033618 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033618;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=rs111033618" 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=rs111033618" 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=RCV000010710 OR RCV000622428 OR RCV001383439" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010710, RCV000622428, RCV001383439" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010710...</a>
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<p>In a 1-year-old Caucasian male with X-linked combined immunodeficiency (<a href="/entry/312863">312863</a>), <a href="#24" class="mim-tip-reference" title="Sharfe, N., Shahar, M., Roifman, C. M. <strong>An interleukin-2 receptor gamma chain mutation with normal thymus morphology.</strong> J. Clin. Invest. 100: 3036-3043, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9399950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9399950</a>] [<a href="https://doi.org/10.1172/JCI119858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9399950">Sharfe et al. (1997)</a> identified an arg222-to-cys (R222C) mutation in the IL2RG gene. The mutation occurs in the extracellular domain of the protein, which was predicted to affect ligand binding. The authors noted that the mutation was distinctive in that the protein was stable enough to be expressed at the cell surface. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9399950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010711" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010711" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010711</a>
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<p>In a boy with a relatively mild form of X-linked SCID (<a href="/entry/300400">300400</a>), <a href="#27" class="mim-tip-reference" title="Speckmann, C., Pannicke, U., Wiech, E., Schwarz, K., Fisch, P., Friedrich, W., Neihues, T., Gilmour, K., Buiting, K., Schlesier, M., Eibel, H., Rohr, J., Superti-Furga, A., Gross-Wieltsch, U., Ehl, S. <strong>Clinical and immunological consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency.</strong> Blood 112: 4090-4097, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728247</a>] [<a href="https://doi.org/10.1182/blood-2008-04-153361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18728247">Speckmann et al. (2008)</a> identified a 466T-C transition in the IL2RG gene, resulting in a leu151-to-pro (L151P) substitution. The mutation was inherited from his unaffected mother. Genetic analysis of peripheral blood cells in the patient showed a dual signal, with the wildtype IL2RG gene in T cells and a mutant IL2RG gene in B cells, NK cells, and granulocytes. The findings were consistent with reversion of the L151P mutation within a common T-cell precursor in the patient. The patient had normal T-cell function, despite low levels of T cells, and impaired B cell antibody response. Functional analysis with mutant IL2RG showed a poor response to IL2 in B cells. The absence of mutated T cells in the patient suggested that mutant IL2RG did not allow proper T-cell development. In addition, X-inactivation studies in the mother showed that her T cells exclusively expressed the wildtype allele. A similar patient with reversion of mutation in a T-cell progenitor was reported by <a href="#28" class="mim-tip-reference" title="Stephan, V., Wahn, V., Le Deist, F., Dirksen, U., Broker, B., Muller-Fleckenstein, I., Horneff, G., Schroten, H., Fischer, A., de Saint Basile, G. <strong>Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells.</strong> New Eng. J. Med. 335: 1563-1567, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900089</a>] [<a href="https://doi.org/10.1056/NEJM199611213352104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900089">Stephan et al. (1996)</a> (see <a href="#0010">308380.0010</a>). However, <a href="#27" class="mim-tip-reference" title="Speckmann, C., Pannicke, U., Wiech, E., Schwarz, K., Fisch, P., Friedrich, W., Neihues, T., Gilmour, K., Buiting, K., Schlesier, M., Eibel, H., Rohr, J., Superti-Furga, A., Gross-Wieltsch, U., Ehl, S. <strong>Clinical and immunological consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency.</strong> Blood 112: 4090-4097, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728247</a>] [<a href="https://doi.org/10.1182/blood-2008-04-153361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18728247">Speckmann et al. (2008)</a> noted that the patient reported by <a href="#28" class="mim-tip-reference" title="Stephan, V., Wahn, V., Le Deist, F., Dirksen, U., Broker, B., Muller-Fleckenstein, I., Horneff, G., Schroten, H., Fischer, A., de Saint Basile, G. <strong>Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells.</strong> New Eng. J. Med. 335: 1563-1567, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900089</a>] [<a href="https://doi.org/10.1056/NEJM199611213352104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900089">Stephan et al. (1996)</a> ultimately showed a deteriorating course and required bone marrow stem cell transplantation at almost 7 years of age. The findings indicated that close immunologic surveillance is still needed in patients with mutation reversion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8900089+18728247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Cavazzano-Calvo2000" class="mim-tip-reference" title="Cavazzano-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., Selz, F., Hue, C., Certain, S., Casanova, J.-L., Bousso, P., Le Deist, F., Fischer, A. <strong>Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.</strong> Science 288: 669-672, 2000.">Cavazzano-Calvo et al. (2000)</a>; <a href="#Dave2004" class="mim-tip-reference" title="Dave, U. P., Jenkins, N. A., Copeland, N. G. <strong>Gene therapy insertional mutagenesis insights.</strong> Science 303: 333 only, 2004.">Dave et al. (2004)</a>; <a href="#Hacein-Bey-Abina2002" class="mim-tip-reference" title="Hacein-Bey-Abina, S., Le Deist, F., Carlier, F., Bouneaud, C., Hue, C., De Villartay, J.-P., Thrasher, A. J., Wulffraat, N., Sorensen, R., Dupuis-Girod, S., Fischer, A., Cavazzana-Calvo, M. <strong>Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.</strong> New Eng. J. Med. 346: 1185-1193, 2002.">Hacein-Bey-Abina
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Cavazzano-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., Selz, F., Hue, C., Certain, S., Casanova, J.-L., Bousso, P., Le Deist, F., Fischer, A.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10784449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10784449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10784449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Dave, U. P., Jenkins, N. A., Copeland, N. G.
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<strong>Gene therapy insertional mutagenesis insights.</strong>
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Science 303: 333 only, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14726584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14726584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14726584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1091667" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921912" 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/pl00008710" target="_blank">Full Text</a>]
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Hacein-Bey-Abina, S., Le Deist, F., Carlier, F., Bouneaud, C., Hue, C., De Villartay, J.-P., Thrasher, A. J., Wulffraat, N., Sorensen, R., Dupuis-Girod, S., Fischer, A., Cavazzana-Calvo, M.
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<strong>Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.</strong>
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New Eng. J. Med. 346: 1185-1193, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11961146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11961146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11961146" 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/10.1056/NEJMoa012616" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.8266076" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.8266077" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1631559" target="_blank">Full Text</a>]
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<a id="30" class="mim-anchor"></a>
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<a id="Wang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, X., Rickert, M., Garcia, K. C.
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<strong>Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gamma-c receptors.</strong>
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Science 310: 1159-1163, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1117893" target="_blank">Full Text</a>]
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<a id="31" class="mim-anchor"></a>
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<a id="Yu2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yu, X., Almeida, J., Darko, S., van der Burg, M., DeRavin, S. S., Malech, H., Gennery, A., Chinn, I., Markert, M. L., Douek, D. C., Milner, J. D.
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<strong>Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development.</strong>
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J. Allergy Clin. Immun. 133: 1109-1115, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24406074</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24406074[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=24406074" 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.jaci.2013.11.018" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse - updated : 1/23/2014
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/9/2009<br>Paul J. Converse - updated : 5/5/2008<br>Paul J. Converse - updated : 3/21/2008<br>Paul J. Converse - updated : 1/10/2006<br>Cassandra L. Kniffin - reorganized : 10/28/2004<br>Ada Hamosh - updated : 2/2/2004<br>Victor A. McKusick - updated : 5/14/2002<br>Jane Kelly - updated : 1/25/2002<br>Paul J. Converse - updated : 10/22/2001<br>Paul J. Converse - updated : 4/27/2001<br>Stylianos E. Antonarakis - updated : 4/17/2001<br>Ada Hamosh - updated : 5/4/2000<br>Victor A. McKusick - updated : 2/2/2000<br>Victor A. McKusick - updated : 1/21/1999<br>Victor A. McKusick - updated : 2/3/1998<br>Victor A. McKusick - updated : 5/16/1997
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 4/13/1993
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mcolton : 01/30/2015
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 2/11/2014<br>mcolton : 1/23/2014<br>mgross : 12/16/2011<br>wwang : 3/18/2009<br>ckniffin : 3/9/2009<br>mgross : 5/5/2008<br>mgross : 3/21/2008<br>mgross : 4/4/2006<br>terry : 3/16/2006<br>mgross : 1/10/2006<br>carol : 10/28/2004<br>carol : 10/28/2004<br>terry : 10/28/2004<br>ckniffin : 10/27/2004<br>ckniffin : 10/27/2004<br>ckniffin : 10/20/2004<br>alopez : 2/2/2004<br>alopez : 11/10/2003<br>alopez : 6/10/2003<br>terry : 5/14/2002<br>carol : 2/15/2002<br>carol : 2/15/2002<br>terry : 1/25/2002<br>mgross : 10/22/2001<br>mgross : 4/27/2001<br>mgross : 4/17/2001<br>alopez : 5/4/2000<br>mgross : 2/2/2000<br>terry : 1/21/1999<br>dkim : 7/2/1998<br>terry : 6/4/1998<br>alopez : 5/21/1998<br>psherman : 5/20/1998<br>mark : 2/5/1998<br>terry : 2/3/1998<br>carol : 6/23/1997<br>mark : 5/26/1997<br>terry : 5/16/1997<br>terry : 2/13/1997<br>jamie : 12/17/1996<br>jamie : 12/6/1996<br>terry : 11/26/1996<br>terry : 11/6/1996<br>mark : 1/31/1996<br>mark : 9/10/1995<br>carol : 5/16/1994<br>terry : 4/21/1994<br>warfield : 3/31/1994<br>mimadm : 2/27/1994<br>carol : 12/6/1993
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<span class="mim-font">
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<strong>*</strong> 308380
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<div>
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<h3>
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<span class="mim-font">
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INTERLEUKIN 2 RECEPTOR, GAMMA; IL2RG
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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INTERLEUKIN RECEPTOR, COMMON GAMMA CHAIN<br />
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INTERLEUKIN RECEPTOR, GAMMA-C<br />
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CD132 ANTIGEN; CD132
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: IL2RG</em></strong>
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<strong>
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<em>
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Cytogenetic location: Xq13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : X:71,107,404-71,111,577 </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 class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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Xq13.1
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<span class="mim-font">
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Combined immunodeficiency, X-linked, moderate
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</td>
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<span class="mim-font">
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312863
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<td>
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<span class="mim-font">
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X-linked recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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Severe combined immunodeficiency, X-linked
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<span class="mim-font">
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300400
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<span class="mim-font">
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X-linked recessive
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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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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</div>
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<span class="mim-text-font">
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<p>Cytokines are potent, soluble mediators that regulate homeostasis of the immune system. IL2RG is known as the interleukin receptor common gamma chain, or gamma-c, because it heterodimerizes with at least 6 unique cytokine-specific interleukin receptor alpha chains, IL2RA (147730), IL4RA (147781), IL7RA (146661), IL9RA (300007), IL15RA (601070), and IL21RA (605383), to form distinct receptor complexes for the cytokines IL2 (147680), IL4 (147780), IL7 (146660), IL9 (146931), IL15 (600554), and IL21 (605384), respectively. The IL2 and IL21 receptor complexes are heterotrimers that also include a shared beta chain, IL2RB/IL15RB (146710) (Brandt et al., 2007). </p>
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</span>
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<div>
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<br />
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</div>
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<h4>
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<span class="mim-font">
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<strong>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>IL2 affects the growth and differentiation of T cells, B cells, natural killer cells, glioma cells, and cells of the monocyte lineage after specifically interacting with its receptors. The IL2 receptor (IL2R) consists of 2 subunits, alpha (IL2RA) and beta (IL2RB). Takeshita et al. (1992) identified a third IL2R subunit, the gamma chain, and isolated the corresponding cDNA from a human T-cell line. The deduced 369-amino acid protein has a molecular mass of 39.9 kD and shows sequence similarity to members of the cytokine receptor family. Northern blot analysis detected a dominant 1.8-kb mRNA transcript in human T and B cells; a second 3.6-kb mRNA transcript was also detected. No IL2RG mRNA transcripts were detected in human nonlymphoid cells, such as promonocytes, epithelial cells, or hepatocytes. </p><p>Noguchi et al. (1993) found that the IL2RG protein, like the IL2RB protein, contains 2 pairs of conserved cysteines typical of cytokine receptor superfamily proteins. </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>Noguchi et al. (1993) determined that the IL2RG gene contains 8 exons and spans approximately 4.2 kb. Southern blot analysis suggested that the gene is present in single copy. </p><p>Puck et al. (1993) sequenced the IL2RG gene and elucidated its genomic organization. </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 study of somatic cell hybrids, Noguchi et al. (1993) and Puck et al. (1993) independently mapped the IL2RG gene to chromosome Xq13. Relationships to markers in linkage studies suggested that IL2RG and XSCID, the locus for X-linked severe combined immunodeficiency (300400), had the same location. By fluorescence in situ hybridization and PCR amplification of somatic cell hybrid DNAs, Puck et al. (1993) mapped IL2RG to Xq13.1. </p><p>Cao et al. (1993) localized the murine Il2rg gene to the X chromosome between Rsvp and Plp and demonstrated that a defect in the gene is not responsible for the X-linked xid mutation, which maps to the same region; see 300300. </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">
|
|
<p>Functional expression studies by Takeshita et al. (1992) showed that the IL2 receptor gamma chain was necessary for formation of high- and intermediate-affinity IL2 receptors, which consist of alpha-beta-gamma heterotrimers and beta-gamma heterodimers, respectively. Takeshita et al. (1992) concluded that the gamma chain is an indispensable component of the functional IL2 receptor. </p><p>The gamma subunit of the IL2 receptor is a subunit also of the IL4 receptor and of the IL7 receptor, i.e., it is a shared or common component of at least 3 cytokine receptors. The designation 'common gamma chain' (gamma-c) was proposed (Kondo et al., 1993; Noguchi et al., 1993; Russell et al., 1993). </p><p>Russell et al. (1993) suggested that the gamma-c subunit may be shared with the interleukin-9 receptor. The sharing of the gamma subunit by several receptors explained why humans and mice that lack IL2 entirely show milder symptoms than those with IL2RG deficiency. </p><p>Sharfe et al. (1997) stated that the gamma-c chain is shared by 5 interleukin receptor complexes: IL2, IL4, IL7, IL9, and IL15. </p><p>Asao et al. (2001) showed that IL21 binds to IL21R in IL2RG-deficient cell lines, but fails to transduce signals. In cell lines expressing IL2RG, binding and activation of JAK1 (147795), JAK3 (600173), STAT1 (600555), and STAT3 (102582) occurs, indicating that IL2RG is an indispensable subunit of the functional IL21R complex. </p><p>Lamaze et al. (2001) selectively blocked clathrin (see 118960)-dependent endocytosis using dominant-negative mutants of EPS15 (600051) and showed that clathrin-mediated endocytosis of transferrin (190000) was inhibited, while endocytosis of the IL2Rs proceeded normally. Ultrastructural and biochemical experiments showed that clathrin-independent endocytosis of IL2Rs existed constitutively in lymphocytes and was coupled to their association with detergent-resistant membrane domains. Clathrin-independent endocytosis required dynamin (see 602377) and was specifically regulated by Rho family GTPases (see 604980). These results defined novel properties of receptor-mediated endocytosis and established that IL2R is efficiently internalized through this clathrin-independent pathway. </p><p>Using flow cytometry, Corrigall et al. (2001) detected expression of a functional IL2R of intermediate affinity composed solely of IL2RB and IL2RG on fibroblast-like synoviocytes (FLS) obtained from rheumatoid arthritis and osteoarthritis patients. Addition of recombinant IL2, IL1B (147720), or TNFA (191160) independently did not upregulate expression of the receptors on FLS, but IL2 or IL1B significantly increased expression of intracellular tyrosine-phosphorylated proteins and the production of MCP1 (158105). Corrigall et al. (2001) proposed that MCP1 in the synovial membrane serves to recruit macrophages and perpetuate inflammation in the joints of patients with rheumatoid arthritis. </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>Biochemical Features</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>Crystal Structure</em></strong></p><p>
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|
Wang et al. (2005) reported the crystal structure of the quaternary complex of IL2 with IL2RA, IL2RB, and IL2RG at a resolution of 2.3 angstroms. </p><p>LaPorte et al. (2008) reported the crystal structures of the complete set of IL4 and IL13 (147683) type I (IL4RA/IL2RG/IL4) and type II (IL4RA/IL13RA1/IL4 and IL4RA/IL13RA1/IL13) ternary signaling complexes at the 3.0-angstrom level. They noted that the type I receptor complex is more active in regulating Th2 development, whereas the type II receptor complex is not found on T cells and is more active in regulating cells that mediate airway hypersensitivity and mucus secretion. The type I complex revealed a structural basis for the ability of IL2RG to recognize 6 different IL2RG cytokines. </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>In 3 unrelated patients with X-linked severe combined immunodeficiency (300400), Noguchi et al. (1993) identified 3 different mutations in the IL2RG gene (308380.0001-308380.0003). </p><p>In 4 unrelated affected males with SCID Puck et al. (1993) identified unique mutations in the IL2RG gene (308380.0004-308380.0007). </p><p>Pepper et al. (1995) found that of 40 IL2RG mutations found in unrelated SCID males, 6 were point mutations at the CpG dinucleotide at cDNA residues 690-691 encoding amino acid arg226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA residue 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL2 receptor complex. Pepper et al. (1995) stated that mutations at these 2 hotspots constituted more than 20% of all XSCID mutations. </p><p>Leonard (1996) provided a review of the molecular basis of X-linked SCID with a listing of the mutations identified in the IL2RG gene. Fugmann et al. (1998) studied the IL2RG gene in 31 patients with SCID. Among 11 patients with XSCID, 10 different mutations were identified in the IL2RG gene, including 8 novel mutations. </p><p>In a patient with X-linked combined immunodeficiency (312863), Sharfe et al. (1997) identified a mutation in the IL2RG gene (308380.0012), which resulted in a protein that was sufficiently stable to be expressed at the cell surface. Although clinically immunodeficient, the patient had normal numbers of peripheral T and B cells, responded normally to mitogenic stimuli, and had a normal thymus gland. While the T-cell receptor repertoire appeared complete, suggesting normal T-cell differentiation, the patient's T cells demonstrated a reduced ability to bind IL2, resulting in immunodeficiency. </p><p>Cacalano and Johnston (1999) reviewed IL2 signaling in relation to inherited immunodeficiency. Formal genetic proof that the IL2R components are critical for T-cell development came with the identification of patients lacking either IL2RG or JAK3 (600173). These patients presented with phenotypically identical T-negative/B-positive/NK-negative SCID, inherited as an X-linked recessive or an autosomal recessive (600802) disorder, respectively. </p><p>Yu et al. (2014) performed deep sequencing on complementarity-determining region-3 (CDR3) of T-cell receptor (TCR)-beta (see 186930) in CD4 (186940)-positive and CD8 (see 186910)-positive T cells from 2 patients with RAG1 (179615) or IL2RG mutations and autoimmunity and/or granulomatous disease, but not severe immunodeficiency (see 233650 for information on the RAG1-associated phenotype); 5 patients with Omenn syndrome (603554) caused by RAG1 or RAG2 (179616) mutations; 2 patients with Omenn syndrome-like phenotypes caused by a ZAP70 (176947) mutation (see 269840) or by atypical DiGeorge syndrome (188400); and 4 healthy controls. They found that patients with Omenn syndrome due to RAG1 or RAG2 mutations had poor TCR-beta diversity compared with controls and patients with Omenn syndrome not due to RAG1 or RAG2 mutations. The 2 patients with RAG1 or IL2RG mutations associated with autoimmunity and granulomatous disease did not have diminished diversity, but instead had skewed V-J pairing and CDR3 amino acid use. Yu et al. (2014) concluded that RAG enzymatic function may be necessary for normal CDR3 junctional diversity and that aberrant TCR generation, but not numeric diversity, may contribute to immune dysregulation in patients with hypomorphic forms of SCID. </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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<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>13 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">
|
|
<strong>.0001 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</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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IL2RG, LYS97TER
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<br />
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SNP: rs137852507,
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gnomAD: rs137852507,
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ClinVar: RCV000010699
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with X-linked SCID (300400), Noguchi et al. (1993) identified an A-to-T transversion in exon 3 of the IL2RG gene, resulting in a lys97-to-ter (K97X) substitution and a truncation of the C-terminal 251 amino acids of the interleukin-2 receptor gamma chain. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</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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IL2RG, ARG267TER
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<br />
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SNP: rs137852508,
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ClinVar: RCV000030058, RCV000255488
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a patient with X-linked SCID (300400), Noguchi et al. (1993) identified a C-to-T transition in exon 7 of the IL2RG gene, resulting in an arg267-to-ter (R267X) substitution and truncation of 81 amino acids 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>
|
|
<span class="mim-font">
|
|
<strong>.0003 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
IL2RG, SER286TER
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<br />
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|
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SNP: rs137852509,
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gnomAD: rs137852509,
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ClinVar: RCV000010701
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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 patient with X-linked SCID (300400), Noguchi et al. (1993) identified a C-to-A transversion in exon 7 of the IL2RG gene, resulting in a ser286-to-ter (S286X) substitution and the truncation of 62 amino acids of the protein. This patient became known as Bubble Boy David because he lived in an isolation bubble in Houston for a long time and his disease became known as Bubble Boy disease. His early clinical course and immune function were reported by South et al. (1977) and Shearer et al. (1985). A male sib was also affected. His immunodeficiency was characterized by panhypogammaglobulinemia, lymphopenia with diminished T cells (varying from 10 to 40% over 12 years), elevated B cells, and essentially absent proliferation to mitogens or antigens. Following T-depleted haploidentical bone marrow transplantation from his sister, there was no improvement in immune function. He died 124 days posttransplant from an EBV-associated lymphoproliferative syndrome. </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>.0004 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</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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|
|
IL2RG, CYS62TER
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|
<br />
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|
|
SNP: rs111033619,
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|
|
ClinVar: RCV000010702
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked SCID (300400), Puck et al. (1993) identified a 200T-A transversion in exon 2 of the IL2RG gene, resulting in a cys62-to-ter (C62X) substitution. </p>
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, GLY114ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033620,
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|
|
|
|
|
|
|
ClinVar: RCV000010703
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked SCID (300400), Puck et al. (1993) identified a 355G-A transition in exon 3 of the IL2RG gene, resulting in a gly114-to-asp (G114D) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, IVS3DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569480018,
|
|
|
|
|
|
|
|
ClinVar: RCV000010704
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with X-linked SCID (300400) and no detectable IL2RG mRNA, Puck et al. (1993) identified a G-to-A transition in the first position of the splice donor site of intron 3 of the IL2RG gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, ILE153ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033621,
|
|
|
|
|
|
|
|
ClinVar: RCV000010705
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with X-linked SCID (300400), Puck et al. (1993) identified a 472T-A transversion in exon 4 of the IL2RG gene, resulting in an ile153-to-asn (I153N) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, LEU271GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852510,
|
|
|
|
|
|
gnomAD: rs137852510,
|
|
|
|
|
|
ClinVar: RCV000010706, RCV001038281
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected males with X-linked combined immunodeficiency (XCID; 312863), which is phenotypically milder than X-linked severe combined immunodeficiency (300400), Schmalstieg et al. (1995) identified a leu271-to-gln (L271Q) substitution in exon 7 of the IL2RG gene. A normal brother did not have the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, 9-BP DUP, GLN-HIS-TRP INS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776729,
|
|
|
|
|
|
|
|
ClinVar: RCV000010707
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By genetic linkage studies in a large Canadian pedigree with XSCID (300400), Puck et al. (1995) found the source of the mutation in the proband's grandmother. Despite her having 1 affected son and 2 carrier daughters with skewed X inactivation, her T cells did not show the expected skewed inactivation. Single-strand conformation polymorphism analysis of IL2RG in the affected proband demonstrated an abnormality in exon 5; sequencing demonstrated a 9-nucleotide in-frame duplication-insertion resulting in a duplication of 3 extracellular amino acids (glutamine, histidine, and tryptophan) just adjacent to and including the first tryptophan of the WSXWS motif found in all members of the cytokine receptor gene superfamily. The 3 additional amino acids were inserted just before residue 235. Mutation detection in the pedigree confirmed that the founder grandmother's somatic cells had only normal IL2RG, and that the SCID-associated X-chromosome haplotype was inherited by 3 daughters, 1 with a wildtype IL2RG gene and 2 others with the insertional mutation. The findings indicated that the grandmother had germline mosaicism, an unusual finding in females. This X-linked SCID family emphasized the limitations of genetic diagnosis by linkage as compared with direct mutation analysis. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IL2RG, CYS115ARG
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033622,
|
|
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|
|
|
|
|
ClinVar: RCV000010708
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
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<p>In a male infant in whom XSCID (300400) was suspected at 1 year of age, Stephan et al. (1996) identified a 343T-C transition in exon 3 of the IL2RG gene, resulting in a cys115-to-arg (C115R) substitution. The patient's mother was heterozygous for the mutation. A maternal uncle and a maternal granduncle had died of pneumonia at ages 4 months and 6 months, respectively. The affected child had BCG vaccination at the age of 2 weeks. At 6 months of age, he was hospitalized for severe interstitial pneumonia. Physical examination at 1 year of age showed no signs of graft-versus-host disease (GVHD; see 614395) and no abnormalities except for a large abscess in the left lumbar region from which acid-fast bacilli with genetic characteristics of the Calmette-Guerin bacillus were identified. Immunologic investigations showed a normal number of T cells, a high B-cell count, and hypogammaglobulinemia with no detectable specific antibody responses. The skin test for purified protein derivative was positive and there were at least attenuated proliferative responses to antigens and mitogens. These unusual findings led to genetic analysis which showed that the gamma chain of IL2R was not expressed in the patient's B cells. Because of the unexpected presence of circulating mature T cells, Stephan et al. (1996) sorted and analyzed the patient's CD3+ T cells for expression of the gamma-c chain. Surprisingly, expression of this chain by T cells with either the CD4+ or CD8+ phenotype was normal, and sequencing of the IL2RG gene revealed the wildtype sequence at position 343. In contrast, the sorted CD19+ B cells, the sorted CD14+ monocytes, and the polymorphonuclear-cell population had no detectable expression of the gamma-c chain on their surface and contained the C115R mutation. The possibility that the patient's circulating T-cell population was derived from the engraftment of T cells in the mother in utero was excluded by T-cell karyotyping and HLA typing. In addition, the X chromosome present in the patient's T-cell and B-cell populations was assessed by study of 2 microsatellites flanking the IL2RG locus. These cell populations had only 1 X chromosome derived from the mother with the same X chromosome present in both T-cell and B-cell populations. Stephan et al. (1996) suggested that a single reversion event had occurred in a T-cell progenitor that gave rise to a number of diversified T-cell clones. </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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</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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IL2RG, ARG285GLN
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<br />
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SNP: rs111033617,
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gnomAD: rs111033617,
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ClinVar: RCV000010709, RCV003231098
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with T-, B+ X-linked SCID (300400), Clark et al. (1995) identified a 2943G-A transition in the IL2RG gene, resulting in an arg285-to-gln (R285Q) substitution. </p><p>Jones et al. (1997) noted that X-linked SCID is characterized by the absence, or very low numbers, of T cells, with normal or even high numbers of B cells. However, in a boy with SCID who had very low numbers of both B cells and T cells, Jones et al. (1997) identified the R285Q mutation. The patient's mother and a maternal aunt were both found to have unilateral X inactivation in their T cells. Jones et al. (1997) stated that in about one-third of the cases of typical SCIDX1, there is no previous family history. In these families, the suspicion of SCIDX1 is raised by the phenotype and may be confirmed by X inactivation in T cells and/or by mutation analysis. The authors cautioned that the unexpected finding of low B cells may mistakenly suggest an autosomal form of SCID. </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>.0012 COMBINED IMMUNODEFICIENCY, X-LINKED</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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IL2RG, ARG222CYS
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<br />
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SNP: rs111033618,
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ClinVar: RCV000010710, RCV000622428, RCV001383439
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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 1-year-old Caucasian male with X-linked combined immunodeficiency (312863), Sharfe et al. (1997) identified an arg222-to-cys (R222C) mutation in the IL2RG gene. The mutation occurs in the extracellular domain of the protein, which was predicted to affect ligand binding. The authors noted that the mutation was distinctive in that the protein was stable enough to be expressed at the cell surface. </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>.0013 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED</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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IL2RG, LEU151PRO
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<br />
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SNP: rs137852511,
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ClinVar: RCV000010711
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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 boy with a relatively mild form of X-linked SCID (300400), Speckmann et al. (2008) identified a 466T-C transition in the IL2RG gene, resulting in a leu151-to-pro (L151P) substitution. The mutation was inherited from his unaffected mother. Genetic analysis of peripheral blood cells in the patient showed a dual signal, with the wildtype IL2RG gene in T cells and a mutant IL2RG gene in B cells, NK cells, and granulocytes. The findings were consistent with reversion of the L151P mutation within a common T-cell precursor in the patient. The patient had normal T-cell function, despite low levels of T cells, and impaired B cell antibody response. Functional analysis with mutant IL2RG showed a poor response to IL2 in B cells. The absence of mutated T cells in the patient suggested that mutant IL2RG did not allow proper T-cell development. In addition, X-inactivation studies in the mother showed that her T cells exclusively expressed the wildtype allele. A similar patient with reversion of mutation in a T-cell progenitor was reported by Stephan et al. (1996) (see 308380.0010). However, Speckmann et al. (2008) noted that the patient reported by Stephan et al. (1996) ultimately showed a deteriorating course and required bone marrow stem cell transplantation at almost 7 years of age. The findings indicated that close immunologic surveillance is still needed in patients with mutation reversion. </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>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
|
|
Cavazzano-Calvo et al. (2000); Dave et al. (2004); Hacein-Bey-Abina
|
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et al. (2002)
|
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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Asao, H., Okuyama, C., Kumaki, S., Ishii, N., Tsuchiya, S., Foster, D., Sugamura, K.
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<strong>Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex.</strong>
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J. Immun. 167: 1-5, 2001.
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[Full Text: https://doi.org/10.4049/jimmunol.167.1.1]
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<p class="mim-text-font">
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Brandt, K., Singh, P. B., Bulfone-Paus, S., Ruckert, R.
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<strong>Interleukin-21: a new modulator of immunity, infection, and cancer.</strong>
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Cytokine Growth Factor Rev. 18: 223-232, 2007.
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Cavazzano-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., Selz, F., Hue, C., Certain, S., Casanova, J.-L., Bousso, P., Le Deist, F., Fischer, A.
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<strong>Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.</strong>
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Clark, P. A., Lester, T., Genet, S., Jones, A. M., Hendriks, R., Levinsky, R. J., Kinnon, C.
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<strong>Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R-gamma chain gene by single-strand conformation polymorphism analysis.</strong>
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Hum. Genet. 96: 427-432, 1995.
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[PubMed: 7557965]
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Corrigall, V. M., Arastu, M., Khan, S., Shah, C., Fife, M., Smeets, T., Tak, P.-P., Panayi, G. S.
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<strong>Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production.</strong>
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J. Immun. 166: 4141-4147, 2001.
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[PubMed: 11238664]
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Fugmann, S. D., Muller, S., Friedrich, W., Bartram, C. R., Schwarz, K.
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<strong>Mutations in the gene for the common gamma chain (gamma-c) in X-linked severe combined immunodeficiency.</strong>
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Hum. Genet. 103: 730-731, 1998.
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<strong>Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.</strong>
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Jones, A. M., Clark, P. A., Katz, F., Genet, S., McMahon, C., Alterman, L., Cant, A., Kinnon, C.
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Hum. Genet. 99: 677-680, 1997.
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Kondo, M., Takeshita, T., Ishii, N., Nakamura, M., Watanabe, S., Arai, K., Sugamura, K.
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LaPorte, S. L., Juo, Z. S., Vaclavikova, J., Colf, L. A., Qi, X., Heller, N. M., Keegan, A. D., Garcia, K. C.
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<strong>Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.</strong>
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Cell 73: 147-157, 1993.
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[PubMed: 8462096]
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<p class="mim-text-font">
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Pepper, A. E., Buckley, R. H., Small, T. N., Puck, J. M.
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<strong>Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.</strong>
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Am. J. Hum. Genet. 57: 564-571, 1995.
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[PubMed: 7668284]
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</p>
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<li>
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<p class="mim-text-font">
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Puck, J. M., Deschenes, S. M., Porter, J. C., Dutra, A. S., Brown, C. J., Willard, H. F., Henthorn, P. S.
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<strong>The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.</strong>
|
|
Hum. Molec. Genet. 2: 1099-1104, 1993.
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|
|
[PubMed: 8401490]
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[Full Text: https://doi.org/10.1093/hmg/2.8.1099]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Puck, J. M., Pepper, A. E., Bedard, P.-M., Laframboise, R.
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<strong>Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency.</strong>
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|
J. Clin. Invest. 95: 895-899, 1995.
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[PubMed: 7860773]
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Victor A. McKusick : 4/13/1993
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