5138 lines
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Entry
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- *606272 - CYSTINOSIN; CTNS
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- OMIM
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<p>
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<span class="h4">*606272</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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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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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<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/606272">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<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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<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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<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=ENSG00000040531;t=ENST00000046640" 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=1497" 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=606272" 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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<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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<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=ENSG00000040531;t=ENST00000046640" 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_001031681,NM_001374492,NM_001374493,NM_001374494,NM_001374495,NM_001374496,NM_004937,XM_006721463,XM_011523691,XM_011523692,XM_047435501,XR_007065277" 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_004937" 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=606272" 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=05885&isoform_id=05885_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/CTNS" 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/3036840,3036851,5616103,7239176,23273064,49457069,119610900,119610901,119610902,119943110,119943118,158257470,194382316,194387124,269849555,578829744,767991723,767991726,957949207,957949210,957949213,957949216,1755203704,1755203706,1755203708,1755203710,1755203712,2217310334,2462553463,2462553465,2462553468" 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/O60931" 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=1497" 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=ENSG00000040531;t=ENST00000046640" 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=CTNS" 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=CTNS" 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+1497" 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/CTNS" 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:1497" 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/1497" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000046640.9&hgg_start=3636459&hgg_end=3663103&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:2518" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2518" 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/ctns" 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=606272[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=606272[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/ENSG00000040531" 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=CTNS" 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=CTNS" 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=CTNS" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CTNS&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/PA27019" 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:2518" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0039045.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1932872" 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/CTNS#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:1932872" 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/1497/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1497" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00008052;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-050522-352" 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:606272" 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:1497" 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=CTNS&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 22830006, 62332007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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606272
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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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CYSTINOSIN; CTNS
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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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<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=CTNS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CTNS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
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Cytogenetic location: <a href="/geneMap/17/62?start=-3&limit=10&highlight=62">17p13.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:3636459-3663103&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">17:3,636,459-3,663,103</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</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>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
|
</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
|
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</th>
|
|
<th>
|
|
Phenotype
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=219800,219900,219800,219750" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/62?start=-3&limit=10&highlight=62">
|
|
17p13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
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|
|
<td>
|
|
<span class="mim-font">
|
|
Cystinosis, atypical nephropathic
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/219800"> 219800 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
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Cystinosis, late-onset juvenile or adolescent nephropathic
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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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<p><a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> identified a novel gene, CTNS, within the deletion interval on chromosome 17 in patients with nephropathic cystinosis (<a href="/entry/219800">219800</a>). They found that CTNS encodes an integral membrane protein, which they designated cystinosin, that has features of a lysosomal membrane protein. CTNS, a putative cystine transporter, contains 367 amino acids and 7 transmembrane domains. A 2.7-kb transcript of the CTNS gene was strongly expressed in pancreas, kidney (mature and fetal), skeletal muscle, to a lesser extent in placenta and heart, and weakly in lung and liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> determined that the CTNS gene has 12 exons. <a href="#15" class="mim-tip-reference" title="Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A. <strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong> Am. J. Hum. Genet. 69: 712-721, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11505338">Phornphutkul et al. (2001)</a> identified the CTNS promoter as the region encompassing nucleotides -316 to +1 with respect to the transcription start site. This region contains an Sp-1 regulatory element at positions -299 to -293 which, as shown by electrophoretic mobility shift assays, binds Sp-1. The CTNS promoter region shares 41 nucleotides with the promoter region of an adjacent gene, CARKL (SHPK; <a href="/entry/605060">605060</a>), whose start site is 501 bp from the CTNS start site. CARKL is aligned on the other DNA strand in the other direction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537412+11505338" 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="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> found that the marker locus D17S829 was homozygously deleted in 23 of 70 patients with nephropathic cystinosis and mapped a novel gene, CTNS, to the deletion interval. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> identified 11 different mutations in the CTNS gene (see, e.g., <a href="#0001">606272.0001</a>-<a href="#0005">606272.0005</a>), all predicted to cause loss of function of the protein, segregating with nephropathic cystinosis. The most common mutation was a 65-kb deletion (<a href="#0005">606272.0005</a>), found in 23 (33%) of 70 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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="#17" class="mim-tip-reference" title="Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A. <strong>CTNS mutations in an American-based population of cystinosis patients.</strong> Am. J. Hum. Genet. 63: 1352-1362, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>] [<a href="https://doi.org/10.1086/302118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792862">Shotelersuk et al. (1998)</a> performed mutation analysis of 108 American-based nephropathic cystinosis patients and found that 48 (44%) were homozygous for the 'European' 65-kb deletion, 2 had a smaller major deletion, 11 were homozygous and 3 were heterozygous for 753G-A (W138X; <a href="#0003">606272.0003</a>), and 24 had 21 other mutations. In 20 patients (19%), no mutations were found. Of 82 alleles bearing the 65-kb deletion, 38 derived from Germany, 28 from the British Isles, and 4 from Iceland. The 18 new mutations identified in this study included the first reported missense mutation, 2 in-frame deletions, and mutations in patients of African American, Mexican, and Indian ancestry. CTNS mutations were spread throughout the leader sequence, transmembrane, and nontransmembrane regions. According to a cystinosis clinical severity score, homozygotes for the 65-kb deletion and for W138X had average disease, whereas mutations involving the first amino acids prior to transmembrane domains were associated with mild disease. By Northern blot analysis, CTNS was not expressed in patients homozygous for the 65-kb deletion but was expressed in all 15 other patients tested. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792862" 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>Structure predictions suggested that cystinosin is a novel integral lysosomal membrane protein. <a href="#2" class="mim-tip-reference" title="Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M. <strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong> Hum. Molec. Genet. 8: 2507-2514, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>] [<a href="https://doi.org/10.1093/hmg/8.13.2507" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10556299">Attard et al. (1999)</a> examined the predicted effects of mutations on this model of cystinosin. They screened patients with infantile nephropathic cystinosis, those with late-onset cystinosis, and patients whose phenotype did not fit the classic definitions. They identified 23 different mutations in the CTNS gene, 14 of which were novel. Of 25 patients with infantile nephropathic cystinosis, 12 had 2 severely truncating mutations, consistent with a loss of functional protein, and 13 had missense or in-frame deletions, which would result in disruption of transmembrane domains and loss of protein function. Mutations identified in 2 late-onset patients (see, e.g., <a href="#0008">606272.0008</a>) affected functionally unimportant regions of cystinosin, accounting for the patients' milder phenotype. For 3 patients, the age of onset of cystinosis was under 7 years, but the course of the disease was milder than the infantile nephropathic form. This suggested that the missense mutations identified in these individuals (see, e.g., <a href="#0007">606272.0007</a>) allowed production of a functional protein and may also indicate regions of cystinosin that are not functionally important. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10556299" 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>As indicated earlier, identification of the CTNS gene was facilitated by the detection of deletions spanning the cystinosis locus in affected individuals. Two types of deletions were detected, one of approximately 65 kb, which was found in homozygous state in nearly one-third of cystinotic individuals, and a smaller one of 9.5 to 16 kb, which was carried by a single family. Both the larger and the smaller deletion span the 5-prime end of the CTNS gene, covering exons 1 to 10 and 1 to 3, respectively; STS analysis indicated that the larger deletion was the same size in all patients. <a href="#7" class="mim-tip-reference" title="Forestier, L., Jean, G., Attard, M., Cherqui, S., Lewis, C., van't Hoff, W., Broyer, M., Town, M., Antignac, C. <strong>Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay.</strong> Am. J. Hum. Genet. 65: 353-359, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417278</a>] [<a href="https://doi.org/10.1086/302509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417278">Forestier et al. (1999)</a> characterized the deletion breakpoints and demonstrated that, although both deletions occur in regions of repetitive sequences, they are the result of nonhomologous recombination. This type of mechanism suggested that the deletion of approximately 65 kb is not a recurrent mutation, and the results confirmed that it is identical in all patients. Haplotype analysis showed that this large deletion is due to a founder effect that occurred in a white individual, and that it probably arose in the middle of the first millennium. <a href="#7" class="mim-tip-reference" title="Forestier, L., Jean, G., Attard, M., Cherqui, S., Lewis, C., van't Hoff, W., Broyer, M., Town, M., Antignac, C. <strong>Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay.</strong> Am. J. Hum. Genet. 65: 353-359, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417278</a>] [<a href="https://doi.org/10.1086/302509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417278">Forestier et al. (1999)</a> also described a rapid PCR-based assay that will accurately detect both homozygous and heterozygous deletions. They used this assay to show that the 65-kb deletion is present in either the homozygous or the heterozygous state in 76% of cystinotic patients of European origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417278" 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="Touchman, J. W., Anikster, Y., Dietrich, N. L., Braden Maduro, V. V., McDowell, G., Shotelersuk, V., Bouffard, G. G., Beckstrom-Sternberg, S. M., Gahl, W. A., Green, E. D. <strong>The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion.</strong> Genome Res. 10: 165-173, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673275</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10673275[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gr.10.2.165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10673275">Touchman et al. (2000)</a> sequenced 200 kb surrounding the CTNS gene and found that the common cystinosis deletion (<a href="#0005">606272.0005</a>) is approximately 57 rather than 65 kb. The authors identified SHPK, which they designated CARKL, within this deleted region. The findings indicated that patients with the 57-kb deletion in CTNS also have a deletion of CARKL, which may account for phenotypic variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10673275" 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="Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A. <strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong> Am. J. Hum. Genet. 69: 712-721, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11505338">Phornphutkul et al. (2001)</a> identified mutations in the CTNS promoter region in 3 patients with cystinosis (<a href="#0012">606272.0012</a>-<a href="#0014">606272.0014</a>). Each of the promoter mutations drastically reduced CAT activity when inserted into a reporter construct and failed either to cause a mobility shift when exposed to nuclear extract or to compete with the normal oligonucleotide's mobility shift. These mutations had no effect on promoter activity of the CARKL gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11505338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Gahl, W. A., Thoene, J. G., Schneider, J. A. <strong>Cystinosis.</strong> New Eng. J. Med. 347: 111-121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12110740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12110740</a>] [<a href="https://doi.org/10.1056/NEJMra020552" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12110740">Gahl et al. (2002)</a> stated that more than 50 different CTNS mutations had been described in homozygous form in cystinosis. The most common mutation is the 57,257-bp deletion, which is found in homozygous state in approximately 50% of cystinosis patients of northern European descent. The deletion is an ancient founder mutation; more recent CTNS mutations involve alterations in the promoter region, leader sequence, transmembrane domains, or nontransmembrane regions. Mutations include small deletions and insertions and nonsense, missense, and splicing mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12110740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Gahl, W. A., Thoene, J. G., Schneider, J. A. <strong>Cystinosis.</strong> New Eng. J. Med. 347: 111-121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12110740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12110740</a>] [<a href="https://doi.org/10.1056/NEJMra020552" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12110740">Gahl et al. (2002)</a> stated that patients with intermediate cystinosis (<a href="/entry/219900">219900</a>) and patients with ocular, or nonnephropathic, cystinosis (<a href="/entry/219750">219750</a>) generally have 1 severe CTNS mutation (e.g., the 57-kb deletion or a nonsense mutation) and 1 mild mutation, so that part of the transport function of cystinosin is retained. However, homozygosity for a mutation of a conserved amino acid (N323K; <a href="#0016">606272.0016</a>) was observed in 2 sibs in Taiwan with intermediate cystinosis (<a href="#18" class="mim-tip-reference" title="Thoene, J., Lemons, R., Anikster, Y., Mullet, J., Paelicke, K., Lucero, C., Gahl, W., Schneider, J., Shu, S. G., Campbell, H. T. <strong>Mutations of CTNS causing intermediate cystinosis.</strong> Molec. Genet. Metab. 67: 283-293, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444339</a>] [<a href="https://doi.org/10.1006/mgme.1999.2876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444339">Thoene et al., 1999</a>), indicating presumably that the mutation allowed for some residual cystine transport, accounting for the mild clinical presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10444339+12110740" 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="Mason, S., Pepe, G., Dall'Amico, R., Tartaglia, S., Casciani, S., Greco, M., Bencivenga, P., Murer, L., Rizzoni, G., Tenconi, R., Clementi, M. <strong>Mutational spectrum of the CTNS gene in Italy.</strong> Europ. J. Hum. Genet. 11: 503-508, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12825071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12825071</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200993" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12825071">Mason et al. (2003)</a> analyzed the CTNS gene in 42 Italian patients with nephropathic cystinosis and found that the mutation spectrum in this population differed from that previously reported for the northern European population: the 57-kb deletion was present in a lower percentage (17%) and splicing mutations represented 30% of the mutations detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12825071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening for mutations in the CTNS exons and promoter region, <a href="#10" class="mim-tip-reference" title="Kalatzis, V., Cohen-Solal, L., Cordier, B., Frishberg, Y., Kemper, M., Nuutinen, E. M., Legrand, E., Cochat, P., Antignac, C. <strong>Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.</strong> Hum. Mutat. 20: 439-446, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442267</a>] [<a href="https://doi.org/10.1002/humu.10141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12442267">Kalatzis et al. (2002)</a> identified 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, 2 juvenile cystinosis, and 1 associated with an atypical form of the disease (<a href="#0017">606272.0017</a>). These mutations, all situated in the exons or immediately flanking intronic sequences, comprised in-frame insertions and deletions, as well as missense, nonsense, and putative splice site mutations. Since the cloning of CTNS, the authors had screened for mutations in 108 affected individuals, with a high mutation detection rate of 95.8%. The few undetectable mutant alleles segregated mostly in the noninfantile forms, suggesting that these individuals carried mutations either in the introns or in unidentified regulatory sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12442267" 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="Kalatzis, V., Nevo, N., Cherqui, S., Gasnier, B., Antignac, C. <strong>Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.</strong> Hum. Molec. Genet. 13: 1361-1371, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15128704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15128704</a>] [<a href="https://doi.org/10.1093/hmg/ddh152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15128704">Kalatzis et al. (2004)</a> studied the relationship between transport activity and intracellular localization of cystinosin mutants and their associated clinical phenotype. Thirty-one pathogenic mutations (24 missense mutations, 7 in-frame deletions or insertions) were analyzed. Most of the mutations did not alter the lysosomal localization of cystinosin, although 3 partially mislocalized the protein independently of its C-terminal sorting motif, thus confirming the presence of an additional sorting mechanism. Sixteen of 19 mutations associated with infantile cystinosis abolished transport, whereas 3 of 5 mutations associated with juvenile or ocular forms strongly reduced transport. Five atypical, unclassified, or misclassified mutations could be clarified using the transport data and additional genetic information. The authors concluded that impaired transport is the most frequent cause of pathogenicity, with infantile cystinosis generally resulting from a total loss of activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15128704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J. <strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong> Clin. Genet. 76: 486-489, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01222.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19863563">Macias-Vidal et al. (2009)</a> analyzed the CTNS gene in 32 unrelated cystinosis patients, 27 Spanish and 5 Moroccan, and identified homozygous or compound heterozygous mutations in 28 of them; only 1 mutation was detected in 4 patients. All but 2 of the patients had the infantile form of cystinosis and had truncating mutations or mutations affecting conserved amino acids associated with transmembrane regions of the protein. The 2 juvenile cystinosis patients were both compound heterozygotes for a truncating mutation (<a href="#0004">606272.0004</a> and <a href="#0005">606272.0005</a>, respectively) and a missense mutation (S139F; <a href="#0018">606272.0018</a>) in the CTNS gene; the latter had previously been found in a patient with a 'nonclassic,' milder form of nephropathic cystinosis by <a href="#2" class="mim-tip-reference" title="Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M. <strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong> Hum. Molec. Genet. 8: 2507-2514, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>] [<a href="https://doi.org/10.1093/hmg/8.13.2507" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10556299">Attard et al. (1999)</a>, who suggested that the S139F mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10556299+19863563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a promoter trap approach, <a href="#6" class="mim-tip-reference" title="Cherqui, S., Sevin, C., Hamard, G., Kalatzis, V., Sich, M., Pequignot, M. O., Gogat, K., Abitbol, M., Broyer, M., Gubler, M.-C., Antignac, C. <strong>Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis.</strong> Molec. Cell. Biol. 22: 7622-7632, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12370309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12370309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12370309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.22.21.7622-7632.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12370309">Cherqui et al. (2002)</a> created mice expressing a truncated cystinosin protein. In wildtype mice, cystinosin localized to lysosomes and transported cystine at acidic pH, whereas the truncated cystinosin mislocalized to the plasma membrane and lost its cystine transport function. These Ctns -/- mice accumulated cystine in all organs tested, and cystine crystals, pathognomonic for cystinosis, were observed. Ctns -/- mice developed ocular changes similar to those observed in affected individuals, bone defects, and behavioral anomalies. However, Ctns -/- mice did not develop proximal tubulopathy or renal failure. As in cystinosis patients, cysteamine administration aided cystine clearance in Ctns -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12370309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Goodman, S., Khan, M., Sharma, J., Li, Z., Cano, J., Castellanos, C., Estrada, M. V., Gertsman, I., Cherqui, S. <strong>Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.</strong> Molec. Genet. Metab. 134: 309-316, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34823997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34823997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34823997[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.ymgme.2021.11.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34823997">Goodman et al. (2021)</a> transplanted hematopoietic stem and progenitor cells (HSPCs) from a Shpk -/- mouse into a Ctns -/- mouse. The treated Ctns -/- mice had a significant reduction in cystine load in multiple tissues and restoration of Ctns expression compared to untreated mice. The treated mice also had improved kidney morphologic structure compared to untreated Ctns -/- mice. <a href="#9" class="mim-tip-reference" title="Goodman, S., Khan, M., Sharma, J., Li, Z., Cano, J., Castellanos, C., Estrada, M. V., Gertsman, I., Cherqui, S. <strong>Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.</strong> Molec. Genet. Metab. 134: 309-316, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34823997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34823997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34823997[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.ymgme.2021.11.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34823997">Goodman et al. (2021)</a> concluded that absence of SHPK does not alter the ability of HSPCs to rescue cystinosis, and that patients with cystinosis who are homozygous for a common 57-kb deletion (<a href="#0005">606272.0005</a>) on chromosome 17p13, which includes both the CTNS and SHPK genes, would likely benefit from ex vivo gene therapy approaches. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34823997" 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=RCV000004691" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004691" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004691</a>
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<p>In 2 consanguineous families from Pakistan, <a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> found that nephropathic cystinosis (<a href="/entry/219800">219800</a>) was associated with a gly95-to-ter (G95X) mutation in the CTNS gene. Analysis of 5 microsatellites covering a 4-cM interval showed a common haplotype, suggesting that these families may be related. The mutation was a G-to-T transversion at nucleotide 622, which converted GGA (gly) to TGA (stop). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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">rs1567695026 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567695026;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=rs1567695026" 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=rs1567695026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 families from central France, <a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> found that nephropathic cystinosis (<a href="/entry/219800">219800</a>) was associated with hemizygosity for the same 2-bp deletion of the CTNS gene: deletion of TG at 397/399 resulted in a stop codon at the site of the mutation. The 2 families shared a common haplotype that segregated with the deletion. Deletion of the second allele was present in affected members of each family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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> rs113994205 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994205;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/rs113994205?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=rs113994205" 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=rs113994205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908125 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908125;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/rs121908125?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=rs121908125" 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=rs121908125" 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=RCV000004693 OR RCV000723832 OR RCV001276658 OR RCV002512763 OR RCV005089162" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004693, RCV000723832, RCV001276658, RCV002512763, RCV005089162" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004693...</a>
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<p>One family from Northern Ireland and one from Eire were found by <a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> to have the same mutation as the basis of nephropathic cystinosis (<a href="/entry/219800">219800</a>): a TGG-to-TGA transition at nucleotide 753 resulting in a trp138-to-ter (W138X) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" 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="McGowan-Jordan, J., Stoddard, K., Podolsky, L., Orrbine, E., McLaine, P., Town, M., Goodyer, P., MacKenzie, A., Heick, H. <strong>Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.</strong> Europ. J. Hum. Genet. 7: 671-678, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482956</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482956">McGowan-Jordan et al. (1999)</a> found the W138X mutation in 21/40 French Canadian cystinosis chromosomes. In all cases the mutation was on a distinctive haplotype. They found the same haplotype in 2 Irish families with this mutation, supporting the hypothesis that Celtic chromosomes represent an extensive portion of cystinosis chromosomes in French Canada. The studies also suggested a frequently unrecognized contribution from non-Gallic sources in the French Canadian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482956" 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">rs786204501 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204501;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=rs786204501" 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=rs786204501" 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=RCV000004695 OR RCV000169183 OR RCV000258029 OR RCV000723831 OR RCV001843488 OR RCV002516530 OR RCV003917579 OR RCV005089839" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004695, RCV000169183, RCV000258029, RCV000723831, RCV001843488, RCV002516530, RCV003917579, RCV005089839" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004695...</a>
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<p>In 4 families from 3 different continents, <a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al. (1998)</a> found that nephropathic cystinosis (<a href="/entry/219800">219800</a>) was associated with deletion of 4 nucleotides, GACT, at nucleotide 357 of the CTNS gene. This resulted in frameshift and a premature termination. The 4 families did not share a common haplotype, indicating a recurrent mutation. <a href="#12" class="mim-tip-reference" title="Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J. <strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong> Clin. Genet. 76: 486-489, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01222.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19863563">Macias-Vidal et al. (2009)</a> noted that based on numbering from the ATG initiation codon the deletion occurs at nucleotide 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537412+19863563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Spanish patient with juvenile-onset nephropathic cystinosis (<a href="/entry/219900">219900</a>), <a href="#12" class="mim-tip-reference" title="Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J. <strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong> Clin. Genet. 76: 486-489, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01222.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19863563">Macias-Vidal et al. (2009)</a> identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F; <a href="#0018">606272.0018</a>) substitution, and the 4-bp deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19863563" 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=RCV000004696 OR RCV000004697 OR RCV000004698" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004696, RCV000004697, RCV000004698" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004696...</a>
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<p>This common mutation in nephropathic cystinosis (<a href="/entry/219800">219800</a>) was originally reported as a 65-kb deletion. <a href="#19" class="mim-tip-reference" title="Touchman, J. W., Anikster, Y., Dietrich, N. L., Braden Maduro, V. V., McDowell, G., Shotelersuk, V., Bouffard, G. G., Beckstrom-Sternberg, S. M., Gahl, W. A., Green, E. D. <strong>The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion.</strong> Genome Res. 10: 165-173, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673275</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10673275[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gr.10.2.165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10673275">Touchman et al. (2000)</a> sequenced 200 kb surrounding the CTNS gene and found that the deletion is approximately 57 rather than 65 kb. The authors identified SHPK (<a href="/entry/605060">605060</a>), which they designated CARKL, within this deleted region. The findings indicated that the 57-kb deletion includes deletion of CARKL in addition to CTNS, which may account for phenotypic variability in patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10673275" 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 French/British report (<a href="#20" class="mim-tip-reference" title="Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C. <strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong> Nature Genet. 18: 319-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>] [<a href="https://doi.org/10.1038/ng0498-319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537412">Town et al., 1998</a>), 23 (33%) of 70 patients with nephropathic cystinosis had a 65-kb deletion in the CTNS gene. Among American-based patients studied by <a href="#17" class="mim-tip-reference" title="Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A. <strong>CTNS mutations in an American-based population of cystinosis patients.</strong> Am. J. Hum. Genet. 63: 1352-1362, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>] [<a href="https://doi.org/10.1086/302118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792862">Shotelersuk et al. (1998)</a>, 48 (44%) of 108 were homozygous for the 65-kb 'European' deletion. Of 96 alleles from these patients, 82 were assigned a nation of origin; 38 (46%) derived from Germany and 28 (34%) arose from the British Isles. Two apparently unrelated patients with homozygous deletions came from Iceland. In addition to the 48 patients homozygous for the 65-kb deletion, many of the patients may have a single copy of the deletion. An upstream deletion breakpoint needed to be determined before a PCR-based test of heterozygosity for the deletion could be developed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537412+9792862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Gahl, W. A., Thoene, J. G., Schneider, J. A. <strong>Cystinosis.</strong> New Eng. J. Med. 347: 111-121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12110740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12110740</a>] [<a href="https://doi.org/10.1056/NEJMra020552" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12110740">Gahl et al. (2002)</a> stated that the 57-kb deletion is found in the homozygous state in approximately 50% of patients of northern European descent who have cystinosis. This founder mutation, which removes the first 10 exons of CTNS and eliminates expression of the protein, apparently occurred in Germany in approximately 500 A.D. (<a href="#17" class="mim-tip-reference" title="Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A. <strong>CTNS mutations in an American-based population of cystinosis patients.</strong> Am. J. Hum. Genet. 63: 1352-1362, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>] [<a href="https://doi.org/10.1086/302118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792862">Shotelersuk et al., 1998</a>) and spread by migration to other regions, including Iceland. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9792862+12110740" 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="Bendavid, C., Kleta, R., Long, R., Ouspenskaia, M., Muenke, M., Haddad, B. R., Gahl, W. A. <strong>FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis.</strong> Hum. Genet. 115: 510-514, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365816</a>] [<a href="https://doi.org/10.1007/s00439-004-1170-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365816">Bendavid et al. (2004)</a> described a FISH method permitting cytogenetic laboratories to test for the 57-kb deletion, which is found in approximately 60% of patients with cystinosis in the United States and northern Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365816" 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="#21" class="mim-tip-reference" title="Wamelink, M. M. C., Struys, E. A., Jansen, E. E. W., Levtchenko, E. N., Zijlstra, F. S. M., Engelke, U., Blom, H. J., Jakobs, C., Wevers, R. A. <strong>Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.</strong> Hum. Mutat. 29: 532-536, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18186520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18186520</a>] [<a href="https://doi.org/10.1002/humu.20685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18186520">Wamelink et al. (2008)</a> found that cystinosis patients homozygous for the 57-kb deletion had increased urinary sedoheptulose and erythritol compared to patients with other CTNS mutations. Enzyme studies of cultured fibroblasts revealed an 80% reduction in sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. The findings indicated that the CARKL gene encodes sedoheptulokinase, which functions in the pentose phosphate pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18186520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Buntinx, L., Voets, T., Morlion, B., Vangeel, L., Janssen, M., Cornelissen, E., Vriens, J., de Hoon, J., Levtchenko, E. <strong>TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.</strong> Sci. Rep. 6: 35395, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27734949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27734949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27734949[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep35395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27734949">Buntinx et al. (2016)</a> noted that the most common mutation in Northern European patients with cystinosis is the 57-kb deletion in the CTNS gene. This deletion extends into the noncoding region upstream of the start codon of the TRPV1 gene (<a href="/entry/602076">602076</a>), which encodes a capsaicin- and heat-sensitive ion channel. <a href="#5" class="mim-tip-reference" title="Buntinx, L., Voets, T., Morlion, B., Vangeel, L., Janssen, M., Cornelissen, E., Vriens, J., de Hoon, J., Levtchenko, E. <strong>TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.</strong> Sci. Rep. 6: 35395, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27734949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27734949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27734949[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep35395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27734949">Buntinx et al. (2016)</a> found that patients heterozygous for the deletion showed normal sensory responses, whereas patients homozygous for the mutation exhibited a 60% reduction in vasodilation and pain evoked by capsaicin, as well as an increase in heat detection threshold. Responses to cold, mechanical stimuli, or cinnamaldehyde, a TRPA1 (<a href="/entry/604775">604775</a>) agonist, were unaltered. <a href="#5" class="mim-tip-reference" title="Buntinx, L., Voets, T., Morlion, B., Vangeel, L., Janssen, M., Cornelissen, E., Vriens, J., de Hoon, J., Levtchenko, E. <strong>TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.</strong> Sci. Rep. 6: 35395, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27734949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27734949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27734949[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep35395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27734949">Buntinx et al. (2016)</a> concluded that cystinosis patients homozygous for the 57-kb CTNS deletion have a strong reduction of TRPV1 function, possibly accounting for sensory alterations and thermoregulatory deficits in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27734949" 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>Compound Heterozygosity for the 57-kb Deletion</p><p>In a 38-year-old woman who presented with photophobia at 38 years of age but had suffered chronic sensitivity to light (<a href="/entry/219750">219750</a>), <a href="#1" class="mim-tip-reference" title="Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A. <strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong> Pediat. Res. 47: 17-23, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10625078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10625078</a>] [<a href="https://doi.org/10.1203/00006450-200001000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10625078">Anikster et al. (2000)</a> identified compound heterozygosity for the 57-kb deletion and a 928G-A transition, resulting in a glycine to arginine substitution at codon 197 (G197R; <a href="#0011">606272.0011</a>). Compound heterozygosity was also found in 2 additional patients from the same family with ocular cystinosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10625078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Spanish patient with juvenile-onset nephropathic cystinosis (<a href="/entry/219900">219900</a>), <a href="#12" class="mim-tip-reference" title="Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J. <strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong> Clin. Genet. 76: 486-489, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01222.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19863563">Macias-Vidal et al. (2009)</a> identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F; <a href="#0018">606272.0018</a>) substitution, and the 57-kb deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19863563" 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">rs121908126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908126;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=rs121908126" 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=rs121908126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>One of 7 missense mutations in the CTNS gene discovered by <a href="#17" class="mim-tip-reference" title="Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A. <strong>CTNS mutations in an American-based population of cystinosis patients.</strong> Am. J. Hum. Genet. 63: 1352-1362, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>] [<a href="https://doi.org/10.1086/302118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792862">Shotelersuk et al. (1998)</a> in patients with nephropathic cystinosis (<a href="/entry/219800">219800</a>) was a gly169-to-asp (G169D) amino acid substitution. Significant CTNS expression was associated with homozygosity of this mutation. All 7 missense mutations gave rise to amino acid changes either inside a transmembrane domain or in the first amino acid prior to a transmembrane domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792862" 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> rs35086888 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs35086888;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/rs35086888?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=rs35086888" 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=rs35086888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 patients, <a href="#2" class="mim-tip-reference" title="Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M. <strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong> Hum. Molec. Genet. 8: 2507-2514, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>] [<a href="https://doi.org/10.1093/hmg/8.13.2507" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10556299">Attard et al. (1999)</a> found an atypical presentation of cystinosis (see <a href="/entry/219800">219800</a>). Although onset was less than 7 years of age, the course was atypically mild. One of the 3 patients (L18) was homozygous for a G-to-A transition in the CTNS gene, resulting in a val42-to-ile (V42I) substitution in the nonconserved region toward the N terminus. This part of the protein is predicted to lie within the lumen of the lysosome, and the mutation was adjacent to, but would not affect, a potential N-glycosylation site. Thus, the location of the mutation was consistent with a milder phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10556299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs765481486 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs765481486;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/rs765481486?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=rs765481486" 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=rs765481486" 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=RCV001836614 OR RCV002567954" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001836614, RCV002567954" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001836614...</a>
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<p>In a patient typical of late-onset cystinosis (<a href="/entry/219900">219900</a>), <a href="#2" class="mim-tip-reference" title="Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M. <strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong> Hum. Molec. Genet. 8: 2507-2514, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>] [<a href="https://doi.org/10.1093/hmg/8.13.2507" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10556299">Attard et al. (1999)</a> identified an intronic mutation of the CTNS gene, a C-to-G transversion at nucleotide 801 -10. This resulted in the formation of an alternative splice site upstream of the normal site. Sequencing across the exon 7-8 boundary in cDNA showed the homozygous insertion of 9 bases, which would result in the addition of 3 amino acids, pro-cys-ser, at a point immediately adjacent to the second transmembrane domain. Although this occurred in a conserved region, the first cytosolic domain is very small (normally 4 amino acids) and consequently may not be functionally important. The addition of the imino group of proline at this point might be expected to cause disruption of the folding of the polypeptide chain, but is unlikely to enter or interfere with the transmembrane domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10556299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
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CTNS, IVS10AS, C-G, -3
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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> rs113994210 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994210;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/rs113994210?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=rs113994210" 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=rs113994210" 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=RCV000004702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004702</a>
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<p>In a 26-year-old male with ocular nonnephropathic cystinosis (<a href="/entry/219750">219750</a>), <a href="#1" class="mim-tip-reference" title="Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A. <strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong> Pediat. Res. 47: 17-23, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10625078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10625078</a>] [<a href="https://doi.org/10.1203/00006450-200001000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10625078">Anikster et al. (2000)</a> reported a C-to-G transversion at the -3 position of the acceptor splice site of IVS10 of the CTNS gene. This mutation was found in compound heterozygosity with a TCCTT deletion at nucleotide 545. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10625078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 CYSTINOSIS, NEPHROPATHIC</strong>
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CTNS, 5-BP DEL, NT545
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs879758262 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs879758262;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=rs879758262" 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=rs879758262" 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=RCV000004703 OR RCV001358753 OR RCV002527666 OR RCV004730977 OR RCV005091262" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004703, RCV001358753, RCV002527666, RCV004730977, RCV005091262" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004703...</a>
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<p><a href="#17" class="mim-tip-reference" title="Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A. <strong>CTNS mutations in an American-based population of cystinosis patients.</strong> Am. J. Hum. Genet. 63: 1352-1362, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>] [<a href="https://doi.org/10.1086/302118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792862">Shotelersuk et al. (1998)</a> identified a 5-bp deletion starting at nucleotide 545 resulting in an I69R amino acid substitution and a stop codon at position 73 of the CTNS gene in a patient with classic cystinosis (<a href="/entry/219800">219800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792862" 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="0011" class="mim-anchor"></a>
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<h4>
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<strong>.0011 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
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CTNS, GLY197ARG
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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> rs113994207 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994207;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/rs113994207?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=rs113994207" 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=rs113994207" 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=RCV000004704 OR RCV000169004 OR RCV000514820 OR RCV001844005 OR RCV002512766 OR RCV005089163" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004704, RCV000169004, RCV000514820, RCV001844005, RCV002512766, RCV005089163" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004704...</a>
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<p>In a 38-year-old woman who presented with photophobia at 38 years of age but had suffered chronic sensitivity to light (<a href="/entry/219750">219750</a>), <a href="#1" class="mim-tip-reference" title="Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A. <strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong> Pediat. Res. 47: 17-23, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10625078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10625078</a>] [<a href="https://doi.org/10.1203/00006450-200001000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10625078">Anikster et al. (2000)</a> identified a G-to-A transition at nucleotide 928, resulting in a glycine to arginine substitution at codon 197 (G197R). The patient was compound heterozygous for the 57-kb deletion (<a href="#0005">606272.0005</a>). This mutation was also found in 2 additional patients from the same family with ocular cystinosis. Both patients were compound heterozygous for the G197R mutation and the 57-kb deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10625078" 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="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 CYSTINOSIS, NEPHROPATHIC</strong>
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CTNS, -295G-C, PROMOTER
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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> rs112140949 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs112140949;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/rs112140949?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=rs112140949" 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=rs112140949" 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=RCV001655746 OR RCV001826361 OR RCV001836615 OR RCV002568019" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001655746, RCV001826361, RCV001836615, RCV002568019" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001655746...</a>
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<span class="mim-text-font">
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<p>In a woman of Scottish-Irish and Puerto Rican descent with nephropathic cystinosis (<a href="/entry/219800">219800</a>), <a href="#15" class="mim-tip-reference" title="Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A. <strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong> Am. J. Hum. Genet. 69: 712-721, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11505338">Phornphutkul et al. (2001)</a> identified heterozygosity for a 57-kb deletion (<a href="#0005">606272.0005</a>) and a promoter mutation, a G-to-C change at nucleotide -295, involving the Sp-1 regulatory element, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 19% of the wildtype CAT activity when transfected in HeLa cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11505338" 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>.0013 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs887657778 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs887657778;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=rs887657778" 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=rs887657778" 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=RCV000004706" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004706" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004706</a>
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<p>In a girl of German/Norwegian heritage with ocular cystinosis (<a href="/entry/219750">219750</a>), <a href="#15" class="mim-tip-reference" title="Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A. <strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong> Am. J. Hum. Genet. 69: 712-721, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11505338">Phornphutkul et al. (2001)</a> identified heterozygosity for a G197R mutation (<a href="#0011">606272.0011</a>) and a promoter mutation, a G-to-T transversion at nucleotide -303, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 5% of the wildtype CAT activity when transfected in HeLa cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11505338" 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>.0014 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
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CTNS, 1-BP INS, -303T, PROMOTER
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004707</a>
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<p>In a woman with ocular cystinosis (<a href="/entry/219750">219750</a>) reported by <a href="#1" class="mim-tip-reference" title="Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A. <strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong> Pediat. Res. 47: 17-23, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10625078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10625078</a>] [<a href="https://doi.org/10.1203/00006450-200001000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10625078">Anikster et al. (2000)</a>, <a href="#15" class="mim-tip-reference" title="Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A. <strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong> Am. J. Hum. Genet. 69: 712-721, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11505338">Phornphutkul et al. (2001)</a> identified heterozygosity for a G197R mutation (<a href="#0011">606272.0011</a>) and a promoter mutation, insertion of a T after position -303, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 16% of the wildtype CAT activity when transfected in HeLa cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11505338+10625078" 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>.0015 CYSTINOSIS, NEPHROPATHIC</strong>
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CTNS, GLY339ARG
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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> rs121908127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908127;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/rs121908127?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=rs121908127" 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=rs121908127" 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=RCV000004708 OR RCV001193377 OR RCV001781181 OR RCV002512767 OR RCV003904807 OR RCV005089164" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004708, RCV001193377, RCV001781181, RCV002512767, RCV003904807, RCV005089164" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004708...</a>
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<p>In 4 children with nephropathic cystinosis (<a href="/entry/219800">219800</a>) in the Old Order Amish population in southwestern Ohio, <a href="#16" class="mim-tip-reference" title="Rupar, C. A., Matsell, D., Surry, S., Siu, V. <strong>A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population. (Letter)</strong> J. Med. Genet. 38: 615-616, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565547</a>] [<a href="https://doi.org/10.1136/jmg.38.9.615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11565547">Rupar et al. (2001)</a> identified a G-to-A transition at nucleotide 1354. This transition resulted in a glycine-to-arginine substitution at residue 339 (G339R). It was found in homozygous form in affected children and in heterozygous form in an unaffected sib. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11565547" 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>.0016 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</strong>
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CTNS, ASN323LYS
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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> rs121908128 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908128;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/rs121908128?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=rs121908128" 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=rs121908128" 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=RCV000004709 OR RCV002512768 OR RCV003466816" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004709, RCV002512768, RCV003466816" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004709...</a>
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<p><a href="#18" class="mim-tip-reference" title="Thoene, J., Lemons, R., Anikster, Y., Mullet, J., Paelicke, K., Lucero, C., Gahl, W., Schneider, J., Shu, S. G., Campbell, H. T. <strong>Mutations of CTNS causing intermediate cystinosis.</strong> Molec. Genet. Metab. 67: 283-293, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444339</a>] [<a href="https://doi.org/10.1006/mgme.1999.2876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444339">Thoene et al. (1999)</a> described 2 sibs in Taiwan with intermediate cystinosis (<a href="/entry/219900">219900</a>) who had linear growth and weight gain within 2 standard deviations of the mean for their ethnic group until the ages of 13 and 14 years when their plasma creatinine concentrations were 1.2 mg per deciliter and 3.3 mg per deciliter, respectively. They were found to be homozygous for a 1308C-G mutation in the CTNS gene, resulting in the substitution of lysine for the conserved asparagine at position 323 (N323K). Presumably, this mutation allowed for some residual cystine transport, accounting for the mild clinical presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10444339" 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="0017" class="mim-anchor"></a>
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<strong>.0017 CYSTINOSIS, ATYPICAL NEPHROPATHIC</strong>
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CTNS, GLY110VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908129 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908129;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=rs121908129" 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=rs121908129" 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=RCV000004710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004710</a>
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<p>In a patient who had atypical nephropathic cystinosis (see <a href="/entry/219800">219800</a>), presenting with Fanconi syndrome (<a href="/entry/134600">134600</a>) and end-stage renal disease, but surprisingly without extrarenal symptoms even late in life, <a href="#10" class="mim-tip-reference" title="Kalatzis, V., Cohen-Solal, L., Cordier, B., Frishberg, Y., Kemper, M., Nuutinen, E. M., Legrand, E., Cochat, P., Antignac, C. <strong>Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.</strong> Hum. Mutat. 20: 439-446, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442267</a>] [<a href="https://doi.org/10.1002/humu.10141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12442267">Kalatzis et al. (2002)</a> detected a gly110-to-val (G110V) mutation situated in the N-terminal region of the CTNS gene. As this substitution affected a nonconserved residue, it was not expected to have a significant effect, but it involved the last nucleotide of exon 6 and affected CTNS splicing. Aberrant transcripts were produced that induced a frameshift at amino acid position 111 and led to premature protein termination prior to the seventh transmembrane segment; no correctly spliced CTNS transcript could be detected. However, only leukocyte RNA was studied and it was considered possible that G110V did not lead to the same splicing events in all tissues. Misspliced transcripts in the kidney might account for the severe renal phenotype, whereas the presence of a correctly spliced form, even in small amounts, in other organs could explain the lack of extrarenal disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12442267" 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>.0018 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267606754 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606754;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/rs267606754?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=rs267606754" 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=rs267606754" 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=RCV000004711 OR RCV000004712 OR RCV000169140 OR RCV000258030 OR RCV002512769 OR RCV005089165" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004711, RCV000004712, RCV000169140, RCV000258030, RCV002512769, RCV005089165" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004711...</a>
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<p>In 2 unrelated Spanish patients with juvenile-onset nephropathic cystinosis (<a href="/entry/219900">219900</a>), <a href="#12" class="mim-tip-reference" title="Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J. <strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong> Clin. Genet. 76: 486-489, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01222.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19863563">Macias-Vidal et al. (2009)</a> identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F) substitution, and a 4-bp deletion (<a href="#0004">606272.0004</a>) and a 57-kb deletion (<a href="#0005">606272.0005</a>), respectively. The S139F mutation had previously been identified in a patient with 'nonclassic' cystinosis (see <a href="/entry/219800">219800</a>), with onset before age 7 years but a milder course of disease than the infantile nephropathic form, by <a href="#2" class="mim-tip-reference" title="Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M. <strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong> Hum. Molec. Genet. 8: 2507-2514, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>] [<a href="https://doi.org/10.1093/hmg/8.13.2507" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10556299">Attard et al. (1999)</a>, who suggested that the mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10556299+19863563" 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="#Bois1976" class="mim-tip-reference" title="Bois, E., Feingold, J., Frenay, P., Briard, M.-L. <strong>Infantile cystinosis in France: genetics, incidence, geographic distribution.</strong> J. Med. Genet. 13: 434-438, 1976.">Bois et al. (1976)</a>
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Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A.
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<strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong>
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Pediat. Res. 47: 17-23, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10625078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10625078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10625078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M.
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<strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong>
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Hum. Molec. Genet. 8: 2507-2514, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10556299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10556299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10556299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bendavid, C., Kleta, R., Long, R., Ouspenskaia, M., Muenke, M., Haddad, B. R., Gahl, W. A.
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<strong>FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis.</strong>
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Hum. Genet. 115: 510-514, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bois, E., Feingold, J., Frenay, P., Briard, M.-L.
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<strong>Infantile cystinosis in France: genetics, incidence, geographic distribution.</strong>
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J. Med. Genet. 13: 434-438, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1018302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1018302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1018302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Buntinx, L., Voets, T., Morlion, B., Vangeel, L., Janssen, M., Cornelissen, E., Vriens, J., de Hoon, J., Levtchenko, E.
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<strong>TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.</strong>
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Sci. Rep. 6: 35395, 2016. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27734949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27734949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27734949[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=27734949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/srep35395" target="_blank">Full Text</a>]
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Cherqui, S., Sevin, C., Hamard, G., Kalatzis, V., Sich, M., Pequignot, M. O., Gogat, K., Abitbol, M., Broyer, M., Gubler, M.-C., Antignac, C.
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<strong>Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis.</strong>
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Molec. Cell. Biol. 22: 7622-7632, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12370309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12370309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12370309[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=12370309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.22.21.7622-7632.2002" target="_blank">Full Text</a>]
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Forestier, L., Jean, G., Attard, M., Cherqui, S., Lewis, C., van't Hoff, W., Broyer, M., Town, M., Antignac, C.
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<strong>Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay.</strong>
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Am. J. Hum. Genet. 65: 353-359, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417278</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417278" 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/10.1086/302509" target="_blank">Full Text</a>]
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Gahl, W. A., Thoene, J. G., Schneider, J. A.
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<strong>Cystinosis.</strong>
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New Eng. J. Med. 347: 111-121, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12110740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12110740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12110740" 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/NEJMra020552" target="_blank">Full Text</a>]
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Goodman, S., Khan, M., Sharma, J., Li, Z., Cano, J., Castellanos, C., Estrada, M. V., Gertsman, I., Cherqui, S.
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<strong>Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.</strong>
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Molec. Genet. Metab. 134: 309-316, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34823997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34823997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34823997[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=34823997" 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.ymgme.2021.11.006" target="_blank">Full Text</a>]
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Kalatzis, V., Cohen-Solal, L., Cordier, B., Frishberg, Y., Kemper, M., Nuutinen, E. M., Legrand, E., Cochat, P., Antignac, C.
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<strong>Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.</strong>
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Hum. Mutat. 20: 439-446, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442267</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12442267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.10141" target="_blank">Full Text</a>]
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Kalatzis, V., Nevo, N., Cherqui, S., Gasnier, B., Antignac, C.
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<strong>Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.</strong>
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Hum. Molec. Genet. 13: 1361-1371, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15128704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15128704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15128704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh152" target="_blank">Full Text</a>]
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Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J.
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<strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong>
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Clin. Genet. 76: 486-489, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19863563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19863563</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19863563" 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/10.1111/j.1399-0004.2009.01222.x" target="_blank">Full Text</a>]
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Mason, S., Pepe, G., Dall'Amico, R., Tartaglia, S., Casciani, S., Greco, M., Bencivenga, P., Murer, L., Rizzoni, G., Tenconi, R., Clementi, M.
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<strong>Mutational spectrum of the CTNS gene in Italy.</strong>
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Europ. J. Hum. Genet. 11: 503-508, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12825071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12825071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12825071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200993" target="_blank">Full Text</a>]
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McGowan-Jordan, J., Stoddard, K., Podolsky, L., Orrbine, E., McLaine, P., Town, M., Goodyer, P., MacKenzie, A., Heick, H.
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<strong>Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.</strong>
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Europ. J. Hum. Genet. 7: 671-678, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482956</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200349" target="_blank">Full Text</a>]
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Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A.
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<strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong>
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Am. J. Hum. Genet. 69: 712-721, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11505338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11505338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11505338[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=11505338" 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/10.1086/323484" target="_blank">Full Text</a>]
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Rupar, C. A., Matsell, D., Surry, S., Siu, V.
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<strong>A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population. (Letter)</strong>
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J. Med. Genet. 38: 615-616, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11565547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.38.9.615" target="_blank">Full Text</a>]
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Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A.
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<strong>CTNS mutations in an American-based population of cystinosis patients.</strong>
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Am. J. Hum. Genet. 63: 1352-1362, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792862" 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/10.1086/302118" target="_blank">Full Text</a>]
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Thoene, J., Lemons, R., Anikster, Y., Mullet, J., Paelicke, K., Lucero, C., Gahl, W., Schneider, J., Shu, S. G., Campbell, H. T.
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<strong>Mutations of CTNS causing intermediate cystinosis.</strong>
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Molec. Genet. Metab. 67: 283-293, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444339</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10444339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/mgme.1999.2876" target="_blank">Full Text</a>]
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Touchman, J. W., Anikster, Y., Dietrich, N. L., Braden Maduro, V. V., McDowell, G., Shotelersuk, V., Bouffard, G. G., Beckstrom-Sternberg, S. M., Gahl, W. A., Green, E. D.
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<strong>The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion.</strong>
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Genome Res. 10: 165-173, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673275</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10673275[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=10673275" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gr.10.2.165" target="_blank">Full Text</a>]
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Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C.
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<strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong>
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Nature Genet. 18: 319-324, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0498-319" target="_blank">Full Text</a>]
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Wamelink, M. M. C., Struys, E. A., Jansen, E. E. W., Levtchenko, E. N., Zijlstra, F. S. M., Engelke, U., Blom, H. J., Jakobs, C., Wevers, R. A.
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<strong>Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.</strong>
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Hum. Mutat. 29: 532-536, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18186520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18186520</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18186520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20685" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 03/17/2022
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Paul J. Converse - updated : 08/23/2017<br>Marla J. F. O'Neill - updated : 1/13/2010<br>Cassandra L. Kniffin - updated : 7/28/2008<br>George E. Tiller - updated : 9/13/2006<br>Patricia A. Hartz - updated : 3/28/2006<br>Victor A. McKusick - updated : 4/27/2005<br>Marla J. F. O'Neill - updated : 11/3/2004<br>Victor A. McKusick - updated : 1/2/2003<br>Victor A. McKusick - updated : 8/26/2002<br>Michael J. Wright - updated : 7/31/2002<br>Deborah L. Stone - updated : 11/7/2001
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carol : 03/17/2022<br>alopez : 12/11/2017<br>mgross : 08/23/2017<br>mcolton : 04/17/2015<br>wwang : 3/19/2010<br>wwang : 1/26/2010<br>terry : 1/13/2010<br>wwang : 7/29/2008<br>ckniffin : 7/28/2008<br>terry : 11/16/2006<br>alopez : 9/13/2006<br>mgross : 3/31/2006<br>terry : 3/28/2006<br>tkritzer : 5/10/2005<br>terry : 4/27/2005<br>carol : 11/4/2004<br>carol : 11/4/2004<br>tkritzer : 11/3/2004<br>carol : 7/29/2003<br>tkritzer : 1/7/2003<br>tkritzer : 1/6/2003<br>terry : 1/2/2003<br>terry : 11/22/2002<br>tkritzer : 9/6/2002<br>tkritzer : 8/29/2002<br>terry : 8/26/2002<br>cwells : 8/1/2002<br>terry : 7/31/2002<br>carol : 11/7/2001<br>carol : 9/25/2001<br>carol : 9/25/2001<br>carol : 9/25/2001
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</div>
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<div>
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<h3>
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<span class="mim-font">
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CYSTINOSIN; CTNS
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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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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CTNS</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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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 22830006, 62332007;
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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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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17p13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:3,636,459-3,663,103 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="4">
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<span class="mim-font">
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17p13.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Cystinosis, atypical nephropathic
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</span>
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</td>
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<td>
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<span class="mim-font">
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219800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Cystinosis, late-onset juvenile or adolescent nephropathic
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</span>
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</td>
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<td>
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<span class="mim-font">
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219900
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Cystinosis, nephropathic
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</span>
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</td>
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<td>
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<span class="mim-font">
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219800
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</span>
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</td>
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<td>
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|
<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Cystinosis, ocular nonnephropathic
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</span>
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</td>
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<td>
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<span class="mim-font">
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219750
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Town et al. (1998) identified a novel gene, CTNS, within the deletion interval on chromosome 17 in patients with nephropathic cystinosis (219800). They found that CTNS encodes an integral membrane protein, which they designated cystinosin, that has features of a lysosomal membrane protein. CTNS, a putative cystine transporter, contains 367 amino acids and 7 transmembrane domains. A 2.7-kb transcript of the CTNS gene was strongly expressed in pancreas, kidney (mature and fetal), skeletal muscle, to a lesser extent in placenta and heart, and weakly in lung and liver. </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>Town et al. (1998) determined that the CTNS gene has 12 exons. Phornphutkul et al. (2001) identified the CTNS promoter as the region encompassing nucleotides -316 to +1 with respect to the transcription start site. This region contains an Sp-1 regulatory element at positions -299 to -293 which, as shown by electrophoretic mobility shift assays, binds Sp-1. The CTNS promoter region shares 41 nucleotides with the promoter region of an adjacent gene, CARKL (SHPK; 605060), whose start site is 501 bp from the CTNS start site. CARKL is aligned on the other DNA strand in the other direction. </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>Town et al. (1998) found that the marker locus D17S829 was homozygously deleted in 23 of 70 patients with nephropathic cystinosis and mapped a novel gene, CTNS, to the deletion interval. </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">
|
|
<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>Town et al. (1998) identified 11 different mutations in the CTNS gene (see, e.g., 606272.0001-606272.0005), all predicted to cause loss of function of the protein, segregating with nephropathic cystinosis. The most common mutation was a 65-kb deletion (606272.0005), found in 23 (33%) of 70 patients. </p><p>Shotelersuk et al. (1998) performed mutation analysis of 108 American-based nephropathic cystinosis patients and found that 48 (44%) were homozygous for the 'European' 65-kb deletion, 2 had a smaller major deletion, 11 were homozygous and 3 were heterozygous for 753G-A (W138X; 606272.0003), and 24 had 21 other mutations. In 20 patients (19%), no mutations were found. Of 82 alleles bearing the 65-kb deletion, 38 derived from Germany, 28 from the British Isles, and 4 from Iceland. The 18 new mutations identified in this study included the first reported missense mutation, 2 in-frame deletions, and mutations in patients of African American, Mexican, and Indian ancestry. CTNS mutations were spread throughout the leader sequence, transmembrane, and nontransmembrane regions. According to a cystinosis clinical severity score, homozygotes for the 65-kb deletion and for W138X had average disease, whereas mutations involving the first amino acids prior to transmembrane domains were associated with mild disease. By Northern blot analysis, CTNS was not expressed in patients homozygous for the 65-kb deletion but was expressed in all 15 other patients tested. </p><p>Structure predictions suggested that cystinosin is a novel integral lysosomal membrane protein. Attard et al. (1999) examined the predicted effects of mutations on this model of cystinosin. They screened patients with infantile nephropathic cystinosis, those with late-onset cystinosis, and patients whose phenotype did not fit the classic definitions. They identified 23 different mutations in the CTNS gene, 14 of which were novel. Of 25 patients with infantile nephropathic cystinosis, 12 had 2 severely truncating mutations, consistent with a loss of functional protein, and 13 had missense or in-frame deletions, which would result in disruption of transmembrane domains and loss of protein function. Mutations identified in 2 late-onset patients (see, e.g., 606272.0008) affected functionally unimportant regions of cystinosin, accounting for the patients' milder phenotype. For 3 patients, the age of onset of cystinosis was under 7 years, but the course of the disease was milder than the infantile nephropathic form. This suggested that the missense mutations identified in these individuals (see, e.g., 606272.0007) allowed production of a functional protein and may also indicate regions of cystinosin that are not functionally important. </p><p>As indicated earlier, identification of the CTNS gene was facilitated by the detection of deletions spanning the cystinosis locus in affected individuals. Two types of deletions were detected, one of approximately 65 kb, which was found in homozygous state in nearly one-third of cystinotic individuals, and a smaller one of 9.5 to 16 kb, which was carried by a single family. Both the larger and the smaller deletion span the 5-prime end of the CTNS gene, covering exons 1 to 10 and 1 to 3, respectively; STS analysis indicated that the larger deletion was the same size in all patients. Forestier et al. (1999) characterized the deletion breakpoints and demonstrated that, although both deletions occur in regions of repetitive sequences, they are the result of nonhomologous recombination. This type of mechanism suggested that the deletion of approximately 65 kb is not a recurrent mutation, and the results confirmed that it is identical in all patients. Haplotype analysis showed that this large deletion is due to a founder effect that occurred in a white individual, and that it probably arose in the middle of the first millennium. Forestier et al. (1999) also described a rapid PCR-based assay that will accurately detect both homozygous and heterozygous deletions. They used this assay to show that the 65-kb deletion is present in either the homozygous or the heterozygous state in 76% of cystinotic patients of European origin. </p><p>Touchman et al. (2000) sequenced 200 kb surrounding the CTNS gene and found that the common cystinosis deletion (606272.0005) is approximately 57 rather than 65 kb. The authors identified SHPK, which they designated CARKL, within this deleted region. The findings indicated that patients with the 57-kb deletion in CTNS also have a deletion of CARKL, which may account for phenotypic variability. </p><p>Phornphutkul et al. (2001) identified mutations in the CTNS promoter region in 3 patients with cystinosis (606272.0012-606272.0014). Each of the promoter mutations drastically reduced CAT activity when inserted into a reporter construct and failed either to cause a mobility shift when exposed to nuclear extract or to compete with the normal oligonucleotide's mobility shift. These mutations had no effect on promoter activity of the CARKL gene. </p><p>Gahl et al. (2002) stated that more than 50 different CTNS mutations had been described in homozygous form in cystinosis. The most common mutation is the 57,257-bp deletion, which is found in homozygous state in approximately 50% of cystinosis patients of northern European descent. The deletion is an ancient founder mutation; more recent CTNS mutations involve alterations in the promoter region, leader sequence, transmembrane domains, or nontransmembrane regions. Mutations include small deletions and insertions and nonsense, missense, and splicing mutations. </p><p>Gahl et al. (2002) stated that patients with intermediate cystinosis (219900) and patients with ocular, or nonnephropathic, cystinosis (219750) generally have 1 severe CTNS mutation (e.g., the 57-kb deletion or a nonsense mutation) and 1 mild mutation, so that part of the transport function of cystinosin is retained. However, homozygosity for a mutation of a conserved amino acid (N323K; 606272.0016) was observed in 2 sibs in Taiwan with intermediate cystinosis (Thoene et al., 1999), indicating presumably that the mutation allowed for some residual cystine transport, accounting for the mild clinical presentation. </p><p>Mason et al. (2003) analyzed the CTNS gene in 42 Italian patients with nephropathic cystinosis and found that the mutation spectrum in this population differed from that previously reported for the northern European population: the 57-kb deletion was present in a lower percentage (17%) and splicing mutations represented 30% of the mutations detected. </p><p>By screening for mutations in the CTNS exons and promoter region, Kalatzis et al. (2002) identified 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, 2 juvenile cystinosis, and 1 associated with an atypical form of the disease (606272.0017). These mutations, all situated in the exons or immediately flanking intronic sequences, comprised in-frame insertions and deletions, as well as missense, nonsense, and putative splice site mutations. Since the cloning of CTNS, the authors had screened for mutations in 108 affected individuals, with a high mutation detection rate of 95.8%. The few undetectable mutant alleles segregated mostly in the noninfantile forms, suggesting that these individuals carried mutations either in the introns or in unidentified regulatory sequences. </p><p>Kalatzis et al. (2004) studied the relationship between transport activity and intracellular localization of cystinosin mutants and their associated clinical phenotype. Thirty-one pathogenic mutations (24 missense mutations, 7 in-frame deletions or insertions) were analyzed. Most of the mutations did not alter the lysosomal localization of cystinosin, although 3 partially mislocalized the protein independently of its C-terminal sorting motif, thus confirming the presence of an additional sorting mechanism. Sixteen of 19 mutations associated with infantile cystinosis abolished transport, whereas 3 of 5 mutations associated with juvenile or ocular forms strongly reduced transport. Five atypical, unclassified, or misclassified mutations could be clarified using the transport data and additional genetic information. The authors concluded that impaired transport is the most frequent cause of pathogenicity, with infantile cystinosis generally resulting from a total loss of activity. </p><p>Macias-Vidal et al. (2009) analyzed the CTNS gene in 32 unrelated cystinosis patients, 27 Spanish and 5 Moroccan, and identified homozygous or compound heterozygous mutations in 28 of them; only 1 mutation was detected in 4 patients. All but 2 of the patients had the infantile form of cystinosis and had truncating mutations or mutations affecting conserved amino acids associated with transmembrane regions of the protein. The 2 juvenile cystinosis patients were both compound heterozygotes for a truncating mutation (606272.0004 and 606272.0005, respectively) and a missense mutation (S139F; 606272.0018) in the CTNS gene; the latter had previously been found in a patient with a 'nonclassic,' milder form of nephropathic cystinosis by Attard et al. (1999), who suggested that the S139F mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Using a promoter trap approach, Cherqui et al. (2002) created mice expressing a truncated cystinosin protein. In wildtype mice, cystinosin localized to lysosomes and transported cystine at acidic pH, whereas the truncated cystinosin mislocalized to the plasma membrane and lost its cystine transport function. These Ctns -/- mice accumulated cystine in all organs tested, and cystine crystals, pathognomonic for cystinosis, were observed. Ctns -/- mice developed ocular changes similar to those observed in affected individuals, bone defects, and behavioral anomalies. However, Ctns -/- mice did not develop proximal tubulopathy or renal failure. As in cystinosis patients, cysteamine administration aided cystine clearance in Ctns -/- mice. </p><p>Goodman et al. (2021) transplanted hematopoietic stem and progenitor cells (HSPCs) from a Shpk -/- mouse into a Ctns -/- mouse. The treated Ctns -/- mice had a significant reduction in cystine load in multiple tissues and restoration of Ctns expression compared to untreated mice. The treated mice also had improved kidney morphologic structure compared to untreated Ctns -/- mice. Goodman et al. (2021) concluded that absence of SHPK does not alter the ability of HSPCs to rescue cystinosis, and that patients with cystinosis who are homozygous for a common 57-kb deletion (606272.0005) on chromosome 17p13, which includes both the CTNS and SHPK genes, would likely benefit from ex vivo gene therapy approaches. </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>18 Selected Examples):</strong>
|
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</span>
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</h4>
|
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<div>
|
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 CYSTINOSIS, NEPHROPATHIC</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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CTNS, GLY95TER
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<br />
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SNP: rs121908124,
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ClinVar: RCV000004691
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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 2 consanguineous families from Pakistan, Town et al. (1998) found that nephropathic cystinosis (219800) was associated with a gly95-to-ter (G95X) mutation in the CTNS gene. Analysis of 5 microsatellites covering a 4-cM interval showed a common haplotype, suggesting that these families may be related. The mutation was a G-to-T transversion at nucleotide 622, which converted GGA (gly) to TGA (stop). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 CYSTINOSIS, NEPHROPATHIC</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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CTNS, 2-BP DEL, 397TG
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<br />
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SNP: rs1567695026,
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ClinVar: RCV000004692
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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 2 families from central France, Town et al. (1998) found that nephropathic cystinosis (219800) was associated with hemizygosity for the same 2-bp deletion of the CTNS gene: deletion of TG at 397/399 resulted in a stop codon at the site of the mutation. The 2 families shared a common haplotype that segregated with the deletion. Deletion of the second allele was present in affected members of each family. </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>.0003 CYSTINOSIS, NEPHROPATHIC</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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CTNS, TRP138TER
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<br />
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SNP: rs113994205, rs121908125,
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gnomAD: rs113994205, rs121908125,
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ClinVar: RCV000004693, RCV000723832, RCV001276658, RCV002512763, RCV005089162
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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>One family from Northern Ireland and one from Eire were found by Town et al. (1998) to have the same mutation as the basis of nephropathic cystinosis (219800): a TGG-to-TGA transition at nucleotide 753 resulting in a trp138-to-ter (W138X) nonsense mutation. </p><p>McGowan-Jordan et al. (1999) found the W138X mutation in 21/40 French Canadian cystinosis chromosomes. In all cases the mutation was on a distinctive haplotype. They found the same haplotype in 2 Irish families with this mutation, supporting the hypothesis that Celtic chromosomes represent an extensive portion of cystinosis chromosomes in French Canada. The studies also suggested a frequently unrecognized contribution from non-Gallic sources in the French Canadian population. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 CYSTINOSIS, NEPHROPATHIC</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">
|
|
CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE, INCLUDED
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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CTNS, 4-BP DEL, 18GACT
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<br />
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SNP: rs786204501,
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ClinVar: RCV000004695, RCV000169183, RCV000258029, RCV000723831, RCV001843488, RCV002516530, RCV003917579, RCV005089839
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 4 families from 3 different continents, Town et al. (1998) found that nephropathic cystinosis (219800) was associated with deletion of 4 nucleotides, GACT, at nucleotide 357 of the CTNS gene. This resulted in frameshift and a premature termination. The 4 families did not share a common haplotype, indicating a recurrent mutation. Macias-Vidal et al. (2009) noted that based on numbering from the ATG initiation codon the deletion occurs at nucleotide 18. </p><p>In a Spanish patient with juvenile-onset nephropathic cystinosis (219900), Macias-Vidal et al. (2009) identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F; 606272.0018) substitution, and the 4-bp deletion. </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>.0005 CYSTINOSIS, NEPHROPATHIC</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">
|
|
CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE, INCLUDED<br />
|
|
CYSTINOSIS, OCULAR NONNEPHROPATHIC, INCLUDED
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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CTNS, 57-KB DEL
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<br />
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ClinVar: RCV000004696, RCV000004697, RCV000004698
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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>This common mutation in nephropathic cystinosis (219800) was originally reported as a 65-kb deletion. Touchman et al. (2000) sequenced 200 kb surrounding the CTNS gene and found that the deletion is approximately 57 rather than 65 kb. The authors identified SHPK (605060), which they designated CARKL, within this deleted region. The findings indicated that the 57-kb deletion includes deletion of CARKL in addition to CTNS, which may account for phenotypic variability in patients. </p><p>In a French/British report (Town et al., 1998), 23 (33%) of 70 patients with nephropathic cystinosis had a 65-kb deletion in the CTNS gene. Among American-based patients studied by Shotelersuk et al. (1998), 48 (44%) of 108 were homozygous for the 65-kb 'European' deletion. Of 96 alleles from these patients, 82 were assigned a nation of origin; 38 (46%) derived from Germany and 28 (34%) arose from the British Isles. Two apparently unrelated patients with homozygous deletions came from Iceland. In addition to the 48 patients homozygous for the 65-kb deletion, many of the patients may have a single copy of the deletion. An upstream deletion breakpoint needed to be determined before a PCR-based test of heterozygosity for the deletion could be developed. </p><p>Gahl et al. (2002) stated that the 57-kb deletion is found in the homozygous state in approximately 50% of patients of northern European descent who have cystinosis. This founder mutation, which removes the first 10 exons of CTNS and eliminates expression of the protein, apparently occurred in Germany in approximately 500 A.D. (Shotelersuk et al., 1998) and spread by migration to other regions, including Iceland. </p><p>Bendavid et al. (2004) described a FISH method permitting cytogenetic laboratories to test for the 57-kb deletion, which is found in approximately 60% of patients with cystinosis in the United States and northern Europe. </p><p>Wamelink et al. (2008) found that cystinosis patients homozygous for the 57-kb deletion had increased urinary sedoheptulose and erythritol compared to patients with other CTNS mutations. Enzyme studies of cultured fibroblasts revealed an 80% reduction in sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. The findings indicated that the CARKL gene encodes sedoheptulokinase, which functions in the pentose phosphate pathway. </p><p>Buntinx et al. (2016) noted that the most common mutation in Northern European patients with cystinosis is the 57-kb deletion in the CTNS gene. This deletion extends into the noncoding region upstream of the start codon of the TRPV1 gene (602076), which encodes a capsaicin- and heat-sensitive ion channel. Buntinx et al. (2016) found that patients heterozygous for the deletion showed normal sensory responses, whereas patients homozygous for the mutation exhibited a 60% reduction in vasodilation and pain evoked by capsaicin, as well as an increase in heat detection threshold. Responses to cold, mechanical stimuli, or cinnamaldehyde, a TRPA1 (604775) agonist, were unaltered. Buntinx et al. (2016) concluded that cystinosis patients homozygous for the 57-kb CTNS deletion have a strong reduction of TRPV1 function, possibly accounting for sensory alterations and thermoregulatory deficits in these patients. </p><p>Compound Heterozygosity for the 57-kb Deletion</p><p>In a 38-year-old woman who presented with photophobia at 38 years of age but had suffered chronic sensitivity to light (219750), Anikster et al. (2000) identified compound heterozygosity for the 57-kb deletion and a 928G-A transition, resulting in a glycine to arginine substitution at codon 197 (G197R; 606272.0011). Compound heterozygosity was also found in 2 additional patients from the same family with ocular cystinosis. </p><p>In a Spanish patient with juvenile-onset nephropathic cystinosis (219900), Macias-Vidal et al. (2009) identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F; 606272.0018) substitution, and the 57-kb deletion. </p>
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</span>
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</div>
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<div>
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|
<br />
|
|
</div>
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|
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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>.0006 CYSTINOSIS, NEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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|
<span class="mim-text-font">
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|
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|
CTNS, GLY169ASP
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<br />
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|
|
SNP: rs121908126,
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|
|
ClinVar: RCV000004699, RCV002512764
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of 7 missense mutations in the CTNS gene discovered by Shotelersuk et al. (1998) in patients with nephropathic cystinosis (219800) was a gly169-to-asp (G169D) amino acid substitution. Significant CTNS expression was associated with homozygosity of this mutation. All 7 missense mutations gave rise to amino acid changes either inside a transmembrane domain or in the first amino acid prior to a transmembrane domain. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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|
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</div>
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<div>
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|
<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CYSTINOSIS, ATYPICAL NEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, VAL42ILE
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|
<br />
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|
|
SNP: rs35086888,
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|
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|
|
|
gnomAD: rs35086888,
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|
|
|
|
|
ClinVar: RCV000004700, RCV000276289, RCV000333816, RCV000440461, RCV001276655, RCV001699175, RCV002512765, RCV003914807
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 patients, Attard et al. (1999) found an atypical presentation of cystinosis (see 219800). Although onset was less than 7 years of age, the course was atypically mild. One of the 3 patients (L18) was homozygous for a G-to-A transition in the CTNS gene, resulting in a val42-to-ile (V42I) substitution in the nonconserved region toward the N terminus. This part of the protein is predicted to lie within the lumen of the lysosome, and the mutation was adjacent to, but would not affect, a potential N-glycosylation site. Thus, the location of the mutation was consistent with a milder phenotype. </p>
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, IVS7AS, C-G, -10
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs765481486,
|
|
|
|
|
|
gnomAD: rs765481486,
|
|
|
|
|
|
ClinVar: RCV001836614, RCV002567954
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient typical of late-onset cystinosis (219900), Attard et al. (1999) identified an intronic mutation of the CTNS gene, a C-to-G transversion at nucleotide 801 -10. This resulted in the formation of an alternative splice site upstream of the normal site. Sequencing across the exon 7-8 boundary in cDNA showed the homozygous insertion of 9 bases, which would result in the addition of 3 amino acids, pro-cys-ser, at a point immediately adjacent to the second transmembrane domain. Although this occurred in a conserved region, the first cytosolic domain is very small (normally 4 amino acids) and consequently may not be functionally important. The addition of the imino group of proline at this point might be expected to cause disruption of the folding of the polypeptide chain, but is unlikely to enter or interfere with the transmembrane domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, IVS10AS, C-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs113994210,
|
|
|
|
|
|
gnomAD: rs113994210,
|
|
|
|
|
|
ClinVar: RCV000004702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old male with ocular nonnephropathic cystinosis (219750), Anikster et al. (2000) reported a C-to-G transversion at the -3 position of the acceptor splice site of IVS10 of the CTNS gene. This mutation was found in compound heterozygosity with a TCCTT deletion at nucleotide 545. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CYSTINOSIS, NEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, 5-BP DEL, NT545
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs879758262,
|
|
|
|
|
|
|
|
ClinVar: RCV000004703, RCV001358753, RCV002527666, RCV004730977, RCV005091262
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Shotelersuk et al. (1998) identified a 5-bp deletion starting at nucleotide 545 resulting in an I69R amino acid substitution and a stop codon at position 73 of the CTNS gene in a patient with classic cystinosis (219800). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, GLY197ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs113994207,
|
|
|
|
|
|
gnomAD: rs113994207,
|
|
|
|
|
|
ClinVar: RCV000004704, RCV000169004, RCV000514820, RCV001844005, RCV002512766, RCV005089163
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 38-year-old woman who presented with photophobia at 38 years of age but had suffered chronic sensitivity to light (219750), Anikster et al. (2000) identified a G-to-A transition at nucleotide 928, resulting in a glycine to arginine substitution at codon 197 (G197R). The patient was compound heterozygous for the 57-kb deletion (606272.0005). This mutation was also found in 2 additional patients from the same family with ocular cystinosis. Both patients were compound heterozygous for the G197R mutation and the 57-kb deletion. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CYSTINOSIS, NEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, -295G-C, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs112140949,
|
|
|
|
|
|
gnomAD: rs112140949,
|
|
|
|
|
|
ClinVar: RCV001655746, RCV001826361, RCV001836615, RCV002568019
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman of Scottish-Irish and Puerto Rican descent with nephropathic cystinosis (219800), Phornphutkul et al. (2001) identified heterozygosity for a 57-kb deletion (606272.0005) and a promoter mutation, a G-to-C change at nucleotide -295, involving the Sp-1 regulatory element, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 19% of the wildtype CAT activity when transfected in HeLa cells. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, -303G-T, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs887657778,
|
|
|
|
|
|
|
|
ClinVar: RCV000004706
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl of German/Norwegian heritage with ocular cystinosis (219750), Phornphutkul et al. (2001) identified heterozygosity for a G197R mutation (606272.0011) and a promoter mutation, a G-to-T transversion at nucleotide -303, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 5% of the wildtype CAT activity when transfected in HeLa cells. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 CYSTINOSIS, OCULAR NONNEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CTNS, 1-BP INS, -303T, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000004707
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with ocular cystinosis (219750) reported by Anikster et al. (2000), Phornphutkul et al. (2001) identified heterozygosity for a G197R mutation (606272.0011) and a promoter mutation, insertion of a T after position -303, in the CTNS gene. The latter mutation was tested for its effect on promoter activity by generation of a -348 to +1 CTNS-CAT construct and was found to produce 16% of the wildtype CAT activity when transfected in HeLa cells. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 CYSTINOSIS, NEPHROPATHIC</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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CTNS, GLY339ARG
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<br />
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|
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SNP: rs121908127,
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gnomAD: rs121908127,
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|
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ClinVar: RCV000004708, RCV001193377, RCV001781181, RCV002512767, RCV003904807, RCV005089164
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|
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|
|
</span>
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|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 4 children with nephropathic cystinosis (219800) in the Old Order Amish population in southwestern Ohio, Rupar et al. (2001) identified a G-to-A transition at nucleotide 1354. This transition resulted in a glycine-to-arginine substitution at residue 339 (G339R). It was found in homozygous form in affected children and in heterozygous form in an unaffected sib. </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>.0016 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</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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CTNS, ASN323LYS
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<br />
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SNP: rs121908128,
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gnomAD: rs121908128,
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|
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|
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ClinVar: RCV000004709, RCV002512768, RCV003466816
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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>Thoene et al. (1999) described 2 sibs in Taiwan with intermediate cystinosis (219900) who had linear growth and weight gain within 2 standard deviations of the mean for their ethnic group until the ages of 13 and 14 years when their plasma creatinine concentrations were 1.2 mg per deciliter and 3.3 mg per deciliter, respectively. They were found to be homozygous for a 1308C-G mutation in the CTNS gene, resulting in the substitution of lysine for the conserved asparagine at position 323 (N323K). Presumably, this mutation allowed for some residual cystine transport, accounting for the mild clinical presentation. </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>.0017 CYSTINOSIS, ATYPICAL NEPHROPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
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CTNS, GLY110VAL
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<br />
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SNP: rs121908129,
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|
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ClinVar: RCV000004710
|
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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 who had atypical nephropathic cystinosis (see 219800), presenting with Fanconi syndrome (134600) and end-stage renal disease, but surprisingly without extrarenal symptoms even late in life, Kalatzis et al. (2002) detected a gly110-to-val (G110V) mutation situated in the N-terminal region of the CTNS gene. As this substitution affected a nonconserved residue, it was not expected to have a significant effect, but it involved the last nucleotide of exon 6 and affected CTNS splicing. Aberrant transcripts were produced that induced a frameshift at amino acid position 111 and led to premature protein termination prior to the seventh transmembrane segment; no correctly spliced CTNS transcript could be detected. However, only leukocyte RNA was studied and it was considered possible that G110V did not lead to the same splicing events in all tissues. Misspliced transcripts in the kidney might account for the severe renal phenotype, whereas the presence of a correctly spliced form, even in small amounts, in other organs could explain the lack of extrarenal disorders. </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>.0018 CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
CYSTINOSIS, ATYPICAL NEPHROPATHIC, INCLUDED
|
|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
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CTNS, SER139PHE
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<br />
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SNP: rs267606754,
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|
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gnomAD: rs267606754,
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|
|
ClinVar: RCV000004711, RCV000004712, RCV000169140, RCV000258030, RCV002512769, RCV005089165
|
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Spanish patients with juvenile-onset nephropathic cystinosis (219900), Macias-Vidal et al. (2009) identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F) substitution, and a 4-bp deletion (606272.0004) and a 57-kb deletion (606272.0005), respectively. The S139F mutation had previously been identified in a patient with 'nonclassic' cystinosis (see 219800), with onset before age 7 years but a milder course of disease than the infantile nephropathic form, by Attard et al. (1999), who suggested that the mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important. </p>
|
|
</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>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Bois et al. (1976)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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|
Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A.
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|
<strong>Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.</strong>
|
|
Pediat. Res. 47: 17-23, 2000.
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[PubMed: 10625078]
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[Full Text: https://doi.org/10.1203/00006450-200001000-00007]
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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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Attard, M., Jean, G., Forestier, L., Cherqui, S., van't Hoff, W., Broyer, M., Antignac, C., Town, M.
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<strong>Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.</strong>
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Hum. Molec. Genet. 8: 2507-2514, 1999.
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Bendavid, C., Kleta, R., Long, R., Ouspenskaia, M., Muenke, M., Haddad, B. R., Gahl, W. A.
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<strong>FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis.</strong>
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Hum. Genet. 115: 510-514, 2004.
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[PubMed: 15365816]
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[Full Text: https://doi.org/10.1007/s00439-004-1170-2]
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<li>
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<p class="mim-text-font">
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Bois, E., Feingold, J., Frenay, P., Briard, M.-L.
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<strong>Infantile cystinosis in France: genetics, incidence, geographic distribution.</strong>
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J. Med. Genet. 13: 434-438, 1976.
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[PubMed: 1018302]
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[Full Text: https://doi.org/10.1136/jmg.13.6.434]
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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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Buntinx, L., Voets, T., Morlion, B., Vangeel, L., Janssen, M., Cornelissen, E., Vriens, J., de Hoon, J., Levtchenko, E.
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<strong>TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.</strong>
|
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Sci. Rep. 6: 35395, 2016. Note: Electronic Article.
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[PubMed: 27734949]
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[Full Text: https://doi.org/10.1038/srep35395]
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<li>
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<p class="mim-text-font">
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Cherqui, S., Sevin, C., Hamard, G., Kalatzis, V., Sich, M., Pequignot, M. O., Gogat, K., Abitbol, M., Broyer, M., Gubler, M.-C., Antignac, C.
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<strong>Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis.</strong>
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Molec. Cell. Biol. 22: 7622-7632, 2002.
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[PubMed: 12370309]
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[Full Text: https://doi.org/10.1128/MCB.22.21.7622-7632.2002]
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</p>
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<li>
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<p class="mim-text-font">
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Forestier, L., Jean, G., Attard, M., Cherqui, S., Lewis, C., van't Hoff, W., Broyer, M., Town, M., Antignac, C.
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<strong>Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay.</strong>
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Am. J. Hum. Genet. 65: 353-359, 1999.
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[PubMed: 10417278]
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[Full Text: https://doi.org/10.1086/302509]
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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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Gahl, W. A., Thoene, J. G., Schneider, J. A.
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<strong>Cystinosis.</strong>
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New Eng. J. Med. 347: 111-121, 2002.
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[PubMed: 12110740]
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[Full Text: https://doi.org/10.1056/NEJMra020552]
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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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Goodman, S., Khan, M., Sharma, J., Li, Z., Cano, J., Castellanos, C., Estrada, M. V., Gertsman, I., Cherqui, S.
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<strong>Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.</strong>
|
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Molec. Genet. Metab. 134: 309-316, 2021.
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[PubMed: 34823997]
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[Full Text: https://doi.org/10.1016/j.ymgme.2021.11.006]
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</p>
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<li>
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<p class="mim-text-font">
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Kalatzis, V., Cohen-Solal, L., Cordier, B., Frishberg, Y., Kemper, M., Nuutinen, E. M., Legrand, E., Cochat, P., Antignac, C.
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<strong>Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.</strong>
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Hum. Mutat. 20: 439-446, 2002.
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[PubMed: 12442267]
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[Full Text: https://doi.org/10.1002/humu.10141]
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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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Kalatzis, V., Nevo, N., Cherqui, S., Gasnier, B., Antignac, C.
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<strong>Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.</strong>
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Hum. Molec. Genet. 13: 1361-1371, 2004.
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[PubMed: 15128704]
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[Full Text: https://doi.org/10.1093/hmg/ddh152]
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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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Macias-Vidal, J., Rodes, M., Hernandez-Perez, J. M., Vilaseca, M. A., Coll, M. J.
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<strong>Analysis of the CTNS gene in 32 cystinosis patients from Spain. (Letter)</strong>
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Clin. Genet. 76: 486-489, 2009.
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[PubMed: 19863563]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01222.x]
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|
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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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|
Mason, S., Pepe, G., Dall'Amico, R., Tartaglia, S., Casciani, S., Greco, M., Bencivenga, P., Murer, L., Rizzoni, G., Tenconi, R., Clementi, M.
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|
<strong>Mutational spectrum of the CTNS gene in Italy.</strong>
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|
Europ. J. Hum. Genet. 11: 503-508, 2003.
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[PubMed: 12825071]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200993]
|
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|
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|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
McGowan-Jordan, J., Stoddard, K., Podolsky, L., Orrbine, E., McLaine, P., Town, M., Goodyer, P., MacKenzie, A., Heick, H.
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|
<strong>Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.</strong>
|
|
Europ. J. Hum. Genet. 7: 671-678, 1999.
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|
|
|
|
|
[PubMed: 10482956]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200349]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Phornphutkul, C., Anikster, Y., Huizing, M., Braun, P., Brodie, C., Chou, J. Y., Gahl, W. A.
|
|
<strong>The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region.</strong>
|
|
Am. J. Hum. Genet. 69: 712-721, 2001.
|
|
|
|
|
|
[PubMed: 11505338]
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|
|
|
|
[Full Text: https://doi.org/10.1086/323484]
|
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|
|
</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Rupar, C. A., Matsell, D., Surry, S., Siu, V.
|
|
<strong>A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population. (Letter)</strong>
|
|
J. Med. Genet. 38: 615-616, 2001.
|
|
|
|
|
|
[PubMed: 11565547]
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|
|
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|
|
[Full Text: https://doi.org/10.1136/jmg.38.9.615]
|
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|
|
</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Shotelersuk, V., Larson, D., Anikster, Y., McDowell, G., Lemons, R., Bernardini, I., Guo, J., Thoene, J., Gahl, W. A.
|
|
<strong>CTNS mutations in an American-based population of cystinosis patients.</strong>
|
|
Am. J. Hum. Genet. 63: 1352-1362, 1998.
|
|
|
|
|
|
[PubMed: 9792862]
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|
|
|
|
|
[Full Text: https://doi.org/10.1086/302118]
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</p>
|
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</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Thoene, J., Lemons, R., Anikster, Y., Mullet, J., Paelicke, K., Lucero, C., Gahl, W., Schneider, J., Shu, S. G., Campbell, H. T.
|
|
<strong>Mutations of CTNS causing intermediate cystinosis.</strong>
|
|
Molec. Genet. Metab. 67: 283-293, 1999.
|
|
|
|
|
|
[PubMed: 10444339]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mgme.1999.2876]
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Touchman, J. W., Anikster, Y., Dietrich, N. L., Braden Maduro, V. V., McDowell, G., Shotelersuk, V., Bouffard, G. G., Beckstrom-Sternberg, S. M., Gahl, W. A., Green, E. D.
|
|
<strong>The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion.</strong>
|
|
Genome Res. 10: 165-173, 2000.
|
|
|
|
|
|
[PubMed: 10673275]
|
|
|
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|
|
[Full Text: https://doi.org/10.1101/gr.10.2.165]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Town, M., Jean, G., Cherqui, S., Attard, M., Forestier, L., Whitmore, S. A., Callen, D. F., Gribouval, O., Broyer, M., Bates, G. P., van't Hoff, W., Antignac, C.
|
|
<strong>A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.</strong>
|
|
Nature Genet. 18: 319-324, 1998.
|
|
|
|
|
|
[PubMed: 9537412]
|
|
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|
|
[Full Text: https://doi.org/10.1038/ng0498-319]
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Wamelink, M. M. C., Struys, E. A., Jansen, E. E. W., Levtchenko, E. N., Zijlstra, F. S. M., Engelke, U., Blom, H. J., Jakobs, C., Wevers, R. A.
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<strong>Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.</strong>
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Hum. Mutat. 29: 532-536, 2008.
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[PubMed: 18186520]
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[Full Text: https://doi.org/10.1002/humu.20685]
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Hilary J. Vernon - updated : 03/17/2022<br>Paul J. Converse - updated : 08/23/2017<br>Marla J. F. O'Neill - updated : 1/13/2010<br>Cassandra L. Kniffin - updated : 7/28/2008<br>George E. Tiller - updated : 9/13/2006<br>Patricia A. Hartz - updated : 3/28/2006<br>Victor A. McKusick - updated : 4/27/2005<br>Marla J. F. O'Neill - updated : 11/3/2004<br>Victor A. McKusick - updated : 1/2/2003<br>Victor A. McKusick - updated : 8/26/2002<br>Michael J. Wright - updated : 7/31/2002<br>Deborah L. Stone - updated : 11/7/2001
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Ada Hamosh : 9/20/2001
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