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Entry
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- *606718 - SOLUTE CARRIER FAMILY 26 (SULFATE TRANSPORTER), MEMBER 2; SLC26A2
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*606718</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606718">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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</nav>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000155850;t=ENST00000286298" 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=1836" 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=606718" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000155850;t=ENST00000286298" 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_000112,XM_017009191" 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_000112" 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=606718" 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=05990&isoform_id=05990_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/SLC26A2" 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/549988,33338206,33338214,34364757,37590805,100913030,158261739,189069150,254763328,1034644065,2462601223" 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/P50443" 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=1836" 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=ENSG00000155850;t=ENST00000286298" 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=SLC26A2" 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=SLC26A2" 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+1836" 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/SLC26A2" 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:1836" 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/1836" 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=chr5&hgg_gene=ENST00000286298.5&hgg_start=149960758&hgg_end=149987400&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:10994" 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/slc26a2" 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=606718[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=606718[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SLC26A2/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000155850" 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=SLC26A2" 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=SLC26A2" 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=SLC26A2" 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=SLC26A2&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/PA149" 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:10994" 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/FBgn0036770.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:892977" 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/SLC26A2#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:892977" 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/1836/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=1836" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012259;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012259 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00013963;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00013963 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020914;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020914 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030717-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1836" 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=SLC26A2&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> 14870002, 254055004, 58561002, 715672007<br />
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<strong>ICD10CM:</strong> Q77.5<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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606718
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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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SOLUTE CARRIER FAMILY 26 (SULFATE TRANSPORTER), MEMBER 2; SLC26A2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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DTD SULFATE TRANSPORTER; DTDST
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SLC26A2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC26A2</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/5/658?start=-3&limit=10&highlight=658">5q32</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:149960758-149987400&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'})">5:149,960,758-149,987,400</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=600972,256050,256050,222600,222600,226900" 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>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/658?start=-3&limit=10&highlight=658">
|
|
5q32
|
|
</a>
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Achondrogenesis Ib
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/600972"> 600972 </a>
|
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<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">
|
|
Atelosteogenesis, type II
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/256050"> 256050 </a>
|
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<p><a href="#8" class="mim-tip-reference" title="Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S. <strong>The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.</strong> Cell 78: 1073-1087, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7923357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7923357</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7923357">Hastbacka et al. (1994)</a> reported the positional cloning of the gene mutated in diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>) by fine-structure linkage disequilibrium mapping. The gene was found to encode a novel sulfate transporter, and was thus symbolized DTDST. Impaired function of DTDST product would be expected to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause a clinical phenotype such as diastrophic dysplasia. A defect in sulfate transport was demonstrable in fibroblasts from a DTD patient. The full transcript was expected to be 8.4 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7923357" 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="#23" class="mim-tip-reference" title="Satoh, H., Susaki, M., Shukunami, C., Iyama, K., Negoro, T., Hiraki, Y. <strong>Functional analysis of diastrophic dysplasia sulfate transporter: its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.</strong> J. Biol. Chem. 273: 12307-12315, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9575183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9575183</a>] [<a href="https://doi.org/10.1074/jbc.273.20.12307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9575183">Satoh et al. (1998)</a> cloned a rat osteoblastic cell DTDST cDNA encoding a 739-amino acid protein that is 73% identical to the human coding sequence. Northern blot analysis suggested that expression is predominantly in cartilage and intestine. The rat gene contains at least 5 exons. Injection of rat and human DTDST cRNA into frog oocytes induces Na(+)-independent sulfate transport that can be inhibited by extracellular chloride and bicarbonate. <a href="#23" class="mim-tip-reference" title="Satoh, H., Susaki, M., Shukunami, C., Iyama, K., Negoro, T., Hiraki, Y. <strong>Functional analysis of diastrophic dysplasia sulfate transporter: its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.</strong> J. Biol. Chem. 273: 12307-12315, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9575183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9575183</a>] [<a href="https://doi.org/10.1074/jbc.273.20.12307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9575183">Satoh et al. (1998)</a> observed a similar activity profile in chondrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9575183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By positional cloning, <a href="#8" class="mim-tip-reference" title="Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S. <strong>The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.</strong> Cell 78: 1073-1087, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7923357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7923357</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7923357">Hastbacka et al. (1994)</a> mapped the DTDST gene approximately 70 kb proximal to CSF1R on 5q32-q33.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7923357" 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="#8" class="mim-tip-reference" title="Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S. <strong>The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.</strong> Cell 78: 1073-1087, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7923357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7923357</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7923357">Hastbacka et al. (1994)</a> identified point mutations in non-Finnish patients with DTD. Three patients from 3 different countries, Germany, the Netherlands, and France, were found to be heterozygous for a single base deletion in codon 575 (AAG to AG; <a href="#0001">606718.0001</a>). An American patient was found to have a 3-prime splice acceptor site mutation from AG to AC in heterozygous state. A third mutation, found in a Canadian patient, involved a deletion of 1 nucleotide in codon 661 (ACA to AC). This deletion was predicted to lead to a premature translational stop after 5 codons with truncation of the last 10% of the protein, including half of the highly conserved region in the C-terminal cytoplasmic tail. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7923357" 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>Superti-Furga et al. (<a href="#24" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Cohn, D. H., Wilcox, W., van der Harten, H. J., Rimoin, D. L., Lander, E. S., Steinmann, B., Gitzelmann, R. <strong>Defective sulfation of proteoglycans in achondrogenesis type 1B is caused by mutations in the DTDST gene: the disorder is allelic to diastrophic dysplasia. (Abstract)</strong> Am. J. Hum. Genet. 57: A48, 1995."None>1995</a>, <a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">1996</a>) described mutations in the DTDST gene (see <a href="#0001">606718.0001</a> and <a href="#0005">606718.0005</a>-<a href="#0008">606718.0008</a>) in patients with achondrogenesis type IB (<a href="/entry/600972">600972</a>). Hastbacka et al. (<a href="#11" class="mim-tip-reference" title="Hastbacka, J., Wilcox, W. R., Superti-Furga, A., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate transporter gene (DTDST). (Abstract)</strong> Am. J. Hum. Genet. 57: A48, 1995."None>1995</a>, <a href="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">1996</a>) identified mutations in the DTDST gene (see <a href="#0001">606718.0001</a>-<a href="#0004">606718.0004</a>) in atelosteogenesis type II (<a href="/entry/256050">256050</a>). Thus, both of these disorders are allelic to diastrophic dysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528239+8571951" 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="Hastbacka, J., Kerrebrock, A., Mokkala, K., Clines, G., Lovett, M., Kaitila, I., de la Chapelle, A., Lander, E. S. <strong>Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).</strong> Europ. J. Hum. Genet. 7: 664-670, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482955</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482955">Hastbacka et al. (1999)</a> reported identification of a Finnish DTD founder mutation, a GT-to-GC transition in the splice donor site of the previously undescribed 5-prime untranslated exon of the DTDST gene (<a href="#0010">606718.0010</a>). The mutation acts by severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried 2 copies of the mutation in 69 families, 1 copy in 14 families, and no copies in 1 family. Thus, roughly 90% of the Finnish DTD chromosomes carried the splice site mutation, which <a href="#9" class="mim-tip-reference" title="Hastbacka, J., Kerrebrock, A., Mokkala, K., Clines, G., Lovett, M., Kaitila, I., de la Chapelle, A., Lander, E. S. <strong>Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).</strong> Europ. J. Hum. Genet. 7: 664-670, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482955</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482955">Hastbacka et al. (1999)</a> designated DTDST(Fin). Unexpectedly, they found that 9 of the DTD chromosomes having the apparently ancestral haplotype did not carry the Finnish mutation but rather 2 other mutations. Eight of these chromosomes had an R279W mutation (<a href="#0002">606718.0002</a>) and 1 had a V340 deletion (<a href="#0008">606718.0008</a>). One possible explanation was that the 3 DTD mutations arose in a population in which this 'rare' haplotype was in fact common and conferred a heterozygote advantage in this population, resulting in an excess of DTD mutations on this haplotype which were then admixed with a larger population in which the haplotype was rare. There was, however, no evidence to support the existence of such an ancestral population or of a heterozygote advantage conferred by DTD chromosomes. A second possibility was that the chromosomes with the rare haplotype are more prone to mutation, although again there was no evidence to support such a hypothesis. Finally, a third possibility was, of course, that the presence of multiple mutations on a rare haplotype are simply a matter of chance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482955" 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="Karniski, L. P. <strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.</strong> Hum. Molec. Genet. 10: 1485-1490, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448940</a>] [<a href="https://doi.org/10.1093/hmg/10.14.1485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11448940">Karniski (2001)</a> compared the sulfate transport activity of 11 reported DTDST mutations upon expression in Xenopus oocytes. Five mutations, including G255E (<a href="#0003">606718.0003</a>), delta-A1751 (<a href="#0001">606718.0001</a>), R178X (<a href="#0005">606718.0005</a>), and N425D (<a href="#0006">606718.0006</a>) exhibited minimal sulfate transport function. Two mutations, delta-V340 (<a href="#0008">606718.0008</a>) and R279W (<a href="#0002">606718.0002</a>), transported sulfate at rates of 17% and 32%, respectively, of wildtype DTDST. Four mutations, including A715V (<a href="#0004">606718.0004</a>), Q454P (<a href="#0009">606718.0009</a>), and G678V (<a href="#0007">606718.0007</a>), had rates of sulfate transport nearly equal to that of wildtype DTDST. In the Xenopus oocyte expression system, the correlation between residual transport function and the severity of human phenotype was not absolute, suggesting that factors in addition to the intrinsic sulfate transport properties of the DTDST protein may influence the phenotype in individuals with DTDST mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11448940" 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="Rossi, A., Superti-Furga, A. <strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance.</strong> Hum. Mutat. 17: 159-171, 2001. Note: Erratum: Hum. Mutat. 18: 82 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241838</a>] [<a href="https://doi.org/10.1002/humu.1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11241838">Rossi and Superti-Furga (2001)</a> stated that over 30 mutations in the SLC26A2 gene had been observed, including 22 novel mutations that they reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241838" 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="Karniski, L. P. <strong>Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.</strong> Hum. Molec. Genet. 13: 2165-2171, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15294877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15294877</a>] [<a href="https://doi.org/10.1093/hmg/ddh242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15294877">Karniski (2004)</a> expressed DTDST-mediated sulfate transport in human embryonic kidney (HEK) cells and determined that the wildtype protein was glycosylated and localized to the cell plasma membrane. Four mutations, R279W (<a href="#0002">606718.0002</a>), A715V (<a href="#0004">606718.0004</a>), Q454P (<a href="#0009">606718.0009</a>), and C653S (<a href="#0011">606718.0011</a>), stimulated sulfate transport at rates only 39 to 62% of wildtype DTDST and were properly localized, but were underexpressed compared to wildtype DTDST. The Q454P mutant was unique in that it was not properly glycosylated in HEK cells, and the G678V (<a href="#0007">606718.0007</a>) mutant was trapped within the cytoplasm. There was no difference in sulfate transport activity between cells transfected with either the delta-V340 or the G678V mutations and control HEK cells. Individuals with severe achondrogenesis 1B phenotype had null mutations on both DTDST alleles. Heterozygotes for both a null mutation and a partial-function mutation exhibited either atelosteogenesis type 2 or DTD, whereas those homozygous for partial-function mutations exhibited the milder, recessive multiple epiphyseal dysplasia phenotype. In contrast to previous studies in Xenopus laevis oocytes (<a href="#14" class="mim-tip-reference" title="Karniski, L. P. <strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.</strong> Hum. Molec. Genet. 10: 1485-1490, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448940</a>] [<a href="https://doi.org/10.1093/hmg/10.14.1485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11448940">Karniski, 2001</a>), there was a strong correlation between the severity of the phenotype and the level of residual transport function in mammalian cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15294877+11448940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of the original family with de la Chapelle dysplasia (DLCD; see <a href="/entry/256050">256050</a> and <a href="#5" class="mim-tip-reference" title="de la Chapelle, A., Maroteaux, P., Havu, N., Granroth, G. <strong>Une rare dysplasie osseuse letale de transmission recessive autosomique.</strong> Arch. Franc. Pediat. 29: 759-770, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4644462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4644462</a>]" pmid="4644462">de la Chapelle et al., 1972</a>), <a href="#2" class="mim-tip-reference" title="Bonafe, L., Hastbacka, J., de la Chapelle, A., Campos-Xavier, A. B., Chiesa, C., Forlino, A., Superti-Furga, A., Rossi, A. <strong>A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. (Letter)</strong> J. Med. Genet. 45: 827-831, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18708426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18708426</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18708426[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/10.1136/jmg.2007.057158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18708426">Bonafe et al. (2008)</a> identified a homozygous mutation in the SLC26A2 gene (<a href="#0013">606718.0013</a>). The findings confirmed that de la Chapelle dysplasia is allelic to other SLC26A2 disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4644462+18708426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a targeted next-generation sequencing skeletal dysplasia panel, <a href="#1" class="mim-tip-reference" title="Barreda-Bonis, A. C., Barraza-Garcia, J., Parron, M., Pastor, I., Heath, K. E., Gonzalez-Casado, I. <strong>Multiple SLC26A2 mutations occurring in a three-generational family.</strong> Europ. J. Med. Genet. 61: 24-28, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29024831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29024831</a>] [<a href="https://doi.org/10.1016/j.ejmg.2017.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29024831">Barreda-Bonis et al. (2018)</a> identified mutations in the SLC26A2 gene in a 14-year-old-girl and her maternal grandfather with EDM4. The girl was compound heterozygous for the common R279W mutation (<a href="#0002">606718.0002</a>), inherited from her mother, and a S522F mutation (<a href="#0015">606718.0015</a>), inherited from her father. Her grandfather was homozygous for the R279W mutation. The girl's mother was short (-3.53 SD), but was only a carrier of the R279W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29024831" 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>Comparing the severity of ACG IB to that of DTD, <a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> noted that ACG IB patients appeared to have structural DTDST mutations on both chromosomes, whereas no DTD patient had been found to that time with 2 structural mutations in DTDST. Rather, there appeared to be a DTD-specific allele, present at a frequency approaching 1% in the Finnish population, having an intact coding region. This allele gives no detectable mRNA by Northern blot analysis, or at the most a very small amount. They noted that the 1751A deletion mutation (<a href="#0001">606718.0001</a>) results in diastrophic dysplasia when compounded with the presumed reduced-expression allele frequent in Finland (<a href="#0010">606718.0010</a>), but produces ACG IB when compounded with a second structural mutation on the other chromosome, such as N425D (<a href="#0006">606718.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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="#27" class="mim-tip-reference" title="Superti-Furga, A., Rossi, A., Steinmann, B., Gitzelmann, R. <strong>A chondrodysplasia family produced by mutations in the diastrophic dysplasia sulfate transporter gene: genotype/phenotype correlations.</strong> Am. J. Med. Genet. 63: 144-147, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723100</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<144::AID-AJMG25>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8723100">Superti-Furga et al. (1996)</a> reviewed the 3 recessively inherited chondrodysplasias of decreasing severity caused by mutations in the DTDST gene: diastrophic dysplasia, atelosteogenesis type II, and achondrogenesis type IB. Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory mutations usually result in one of the less severe phenotypes. The chondrodysplasias arising at the DTDST locus all have recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723100" 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 Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II, <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> identified compound heterozygosity for the R279W and R178X (<a href="#0005">606718.0005</a>) mutations in the SLC26A2 gene. <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15316973" 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 girl with features suggesting diastrophic dysplasia but with other features usually observed in Desbuquois dysplasia (see <a href="/entry/251450">251450</a>), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), <a href="#20" class="mim-tip-reference" title="Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M. <strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong> Am. J. Med. Genet. 146A: 2920-2924, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925670</a>] [<a href="https://doi.org/10.1002/ajmg.a.32543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925670">Panzer et al. (2008)</a> identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation and a novel A133V mutation (<a href="#0014">606718.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925670" 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="#6" class="mim-tip-reference" title="Forlino, A., Piazza, R., Tiveron, C., Della Torre, S., Tatangelo, L., Bonafe, L., Gualeni, B., Romano, A., Pecora, F., Superti-Furga, A., Cetta, G., Rossi, A. <strong>A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.</strong> Hum. Molec. Genet. 14: 859-871, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15703192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15703192</a>] [<a href="https://doi.org/10.1093/hmg/ddi079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15703192">Forlino et al. (2005)</a> generated Slc26a2-knockin mice with a partial loss of function of the sulfate transporter resulting from abnormal splicing. Homozygous mutant mice were characterized by growth retardation, skeletal dysplasia and joint contractures, recapitulating essential aspects of the human DTD phenotype. The skeletal phenotype included reduced toluidine blue staining of cartilage, chondrocytes of irregular size, delay in the formation of the secondary ossification center and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts. In spite of the generalized nature of the sulfate uptake defect, significant proteoglycan undersulfation was detected only in cartilage. Chondrocyte proliferation and apoptosis studies suggested that reduced proliferation and/or lack of terminal chondrocyte differentiation might contribute to reduced bone growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15703192" 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> rs386833498 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386833498;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/rs386833498?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=rs386833498" 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=rs386833498" 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=RCV000004302 OR RCV000004303 OR RCV000023567 OR RCV000586135 OR RCV000817526 OR RCV002276529" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004302, RCV000004303, RCV000023567, RCV000586135, RCV000817526, RCV002276529" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004302...</a>
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<p>In 3 patients with diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>) from Germany, the Netherlands, and France, respectively, <a href="#8" class="mim-tip-reference" title="Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S. <strong>The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.</strong> Cell 78: 1073-1087, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7923357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7923357</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7923357">Hastbacka et al. (1994)</a> identified heterozygosity for a deletion of 1 nucleotide in codon 575 of the DTD gene (SLC26A2), converting AAG to AG; this mutation resulted in a frameshift, causing a premature translational stop after 9 codons that would eliminate the last 20% of the protein. The deletion destroyed a DdeI site and created a BfaI site, providing a simple assay for the presence of the mutation. The patients presumably carried a different DTD mutation on the other homolog. Examination of 100 normal chromosomes confirmed that the deletion was not a polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7923357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> found that this mutation, which they called the 1751A deletion, results in diastrophic dysplasia when compounded with the presumed reduced-expression allele frequent in Finland (<a href="#0010">606718.0010</a>), but produces achondrogenesis type IB (ACG1B; <a href="/entry/600972">600972</a>) when compounded with a second structural mutation on the other chromosome, such as N425D (<a href="#0006">606718.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>), <a href="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">Hastbacka et al. (1996)</a> identified compound heterozygosity for 1751delA and an 862C-T transition resulting in an R279W substitution (<a href="#0002">606718.0002</a>) in the third extracellular loop. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 ATELOSTEOGENESIS, TYPE II</strong>
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DIASTROPHIC DYSPLASIA, INCLUDED<br />
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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> rs104893915 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893915;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/rs104893915?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=rs104893915" 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=rs104893915" 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=RCV000004305 OR RCV000004306 OR RCV000004307 OR RCV000266165 OR RCV000275762 OR RCV000586600 OR RCV000624686 OR RCV000641290 OR RCV000999764 OR RCV001030752 OR RCV001030753 OR RCV002276530" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004305, RCV000004306, RCV000004307, RCV000266165, RCV000275762, RCV000586600, RCV000624686, RCV000641290, RCV000999764, RCV001030752, RCV001030753, RCV002276530" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004305...</a>
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<p><strong><em>Atelosteogeneis Type II and Diastrophic Dysplasia</em></strong></p><p>
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For discussion of the arg279-to-trp (R279W) mutation in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>) by <a href="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">Hastbacka et al. (1996)</a>, see <a href="#0001">606718.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571951" 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="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">Hastbacka et al. (1996)</a> also found the R279W substitution in compound heterozygous state in 4 patients with diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Rossi, A., van der Harten, H. J., Beemer, F. A., Kleijer, W. J., Gitzelmann, R., Steinmann, B., Superti-Furga, A. <strong>Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.</strong> Hum. Genet. 98: 657-661, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931695</a>] [<a href="https://doi.org/10.1007/s004390050279" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8931695">Rossi et al. (1996)</a> studied fibroblast cultures of 3 new patients with mutations in the DTDST gene: one with diastrophic dysplasia (the least severe of the conditions caused by DTDST mutations), one with the more severe atelosteogenesis type II, and one with an intermediate phenotype designated AO2/DTD. Reduced incorporation of inorganic sulfate into macromolecules was found in all 3. Each of the 3 patients was found to be heterozygous for R279W. In 2 patients (DTD and OA2/DTD), no other structural mutation was found, but PCR amplification and SSCP analysis of fibroblast cDNA showed reduced mRNA levels of the wildtype DTDST allele. <a href="#22" class="mim-tip-reference" title="Rossi, A., van der Harten, H. J., Beemer, F. A., Kleijer, W. J., Gitzelmann, R., Steinmann, B., Superti-Furga, A. <strong>Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.</strong> Hum. Genet. 98: 657-661, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931695</a>] [<a href="https://doi.org/10.1007/s004390050279" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8931695">Rossi et al. (1996)</a> stated that these 2 patients may be compound heterozygotes for the 'Finnish' mutation which had as yet not been characterized at the DNA level and which was known to cause reduced expression of DTDST. The third patient (with AO2) had the R279W mutation compounded with a novel mutation, the deletion of cytosine-418 (<a href="#0012">606718.0012</a>), predicting a frameshift with premature termination. This allele was underrepresented in the cDNA, in accordance with previous observations that premature stop codons reduce mRNA levels. The presence of the DTDST R297W mutation in a total of 11 patients with AO2 or DTD emphasized the overlap between these conditions. This mutation was not found in 8 analyzed patients with achondrogenesis type IB (ACG IB), the clinically most severe member of this family of chondrodysplasias, suggesting that the R279W mutation allows some residual activity of the sulfate transporter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8931695" 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 Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II, <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> identified compound heterozygosity for the R279W and R178X (<a href="#0005">606718.0005</a>) mutations in the SLC26A2 gene. <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15316973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Multiple Epiphyseal Dysplasia 4</em></strong></p><p>
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<a href="#26" class="mim-tip-reference" title="Superti-Furga, A., Neumann, L., Riebel, T., Eich, G., Steinmann, B., Spranger, J., Kunze, J. <strong>Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.</strong> J. Med. Genet. 36: 621-624, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10465113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10465113</a>]" pmid="10465113">Superti-Furga et al. (1999)</a> reported a 36-year-old man with a recessively inherited form of multiple epiphyseal dysplasia (EDM4; <a href="/entry/226900">226900</a>) characterized by tall-normal stature, clubfoot, and an unusual double-layered patella. This man was found to have a homozygous R279W mutation in the DTDST gene product. Both healthy parents were heterozygous for this mutation. Analysis of the proband's fibroblasts showed a sulfate incorporation defect typical of disorders caused by DTDST mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10465113" 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="Huber, C., Odent, S., Rumeur, S., Padovani, P., Penet, C., Cormier-Daire, V., Munnich, A., Le Merrer, M. <strong>Sulphate transporter gene mutations in apparently isolated club foot. (Letter)</strong> J. Med. Genet. 38: 191-192, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11303514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11303514</a>] [<a href="https://doi.org/10.1136/jmg.38.3.191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11303514">Huber et al. (2001)</a> found the R279W mutation in homozygosity in affected members of 2 unrelated sibships with multiple epiphyseal dysplasia, who were initially thought to have isolated clubfoot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11303514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Czarny-Ratajczak, M., Lohiniva, J., Rogala, P., Kozlowski, K., Perala, M., Carter, L., Spector, T. D., Kolodziej, L., Seppanen, U., Glazar, R., Krolewski, J., Latos-Bielenska, A., Ala-Kokko, L. <strong>A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity.</strong> Am. J. Hum. Genet. 69: 969-980, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11565064[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/10.1086/324023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11565064">Czarny-Ratajczak et al. (2001)</a> identified the homozygous R279W mutation in 2 probands with multiple epiphyseal dysplasia and multipartite patella (see <a href="/entry/226900">226900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11565064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a targeted next-generation sequencing skeletal dysplasia panel, <a href="#1" class="mim-tip-reference" title="Barreda-Bonis, A. C., Barraza-Garcia, J., Parron, M., Pastor, I., Heath, K. E., Gonzalez-Casado, I. <strong>Multiple SLC26A2 mutations occurring in a three-generational family.</strong> Europ. J. Med. Genet. 61: 24-28, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29024831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29024831</a>] [<a href="https://doi.org/10.1016/j.ejmg.2017.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29024831">Barreda-Bonis et al. (2018)</a> identified mutations in the SLC26A2 gene in a 14-year-old girl and her maternal grandfather with EDM4. The girl was compound heterozygous for the R279W mutation, inherited from her mother, and a c.1565C-T transition, resulting in a ser522-to-phe (S522F; <a href="#0015">606718.0015</a>) substitution, inherited from her father. Her grandfather was homozygous for the R279W mutation. The girl's mother was short (-3.53 SD), but was only a carrier for the R279W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29024831" 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> rs104893917 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893917;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/rs104893917?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=rs104893917" 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=rs104893917" 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=RCV000004308 OR RCV000675076 OR RCV001851640 OR RCV003230347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004308, RCV000675076, RCV001851640, RCV003230347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004308...</a>
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<p>Patient 3 with atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>) investigated by <a href="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">Hastbacka et al. (1996)</a> was a compound heterozygote for a 791G-A transition in the SLC26A2 gene, leading to a G255E substitution that introduced a negative charge in the highly conserved fifth putative transmembrane domain of the protein, and a 2171C-T transition, leading to an A715V substitution (<a href="#0004">606718.0004</a>) close to the C terminus of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571951" 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>.0004 ATELOSTEOGENESIS, TYPE II</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> rs104893918 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893918;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/rs104893918?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=rs104893918" 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=rs104893918" 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=RCV000004309 OR RCV000675095 OR RCV000797878 OR RCV003472968" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004309, RCV000675095, RCV000797878, RCV003472968" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004309...</a>
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<p>For discussion of the ala715-to-val (A715V) mutation in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>) by <a href="#10" class="mim-tip-reference" title="Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S. <strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong> Am. J. Hum. Genet. 58: 255-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571951</a>]" pmid="8571951">Hastbacka et al. (1996)</a>, see <a href="#0003">606718.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 ACHONDROGENESIS, TYPE IB</strong>
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DIASTROPHIC DYSPLASIA, INCLUDED
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SLC26A2, ARG178TER
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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> rs104893919 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893919;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/rs104893919?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=rs104893919" 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=rs104893919" 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=RCV000004310 OR RCV000023568 OR RCV000175526 OR RCV000411745 OR RCV000412934 OR RCV000590163 OR RCV000690242 OR RCV000779467 OR RCV001030754" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004310, RCV000023568, RCV000175526, RCV000411745, RCV000412934, RCV000590163, RCV000690242, RCV000779467, RCV001030754" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004310...</a>
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<p>In 3 patients with achondrogenesis type IB (ACG1B; <a href="/entry/600972">600972</a>), <a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> found compound heterozygosity for a 559C-T transition in the SLC26A2 gene, resulting in an R178X amino substitution. The nonsense mutation resulted in truncation of approximately 75% of the protein. In each of the 3 cases the other mutant allele was a structural mutation (see, e.g., <a href="#0007">606718.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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 Mexican girl with diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>) presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>), <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> identified compound heterozygosity for the R279W (<a href="#0002">606718.0002</a>) and R178X mutations in the SLC26A2 gene; see <a href="#0002">606718.0002</a>. <a href="#16" class="mim-tip-reference" title="Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P. <strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong> Am. J. Med. Genet. 129A: 190-192, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>] [<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15316973">Macias-Gomez et al. (2004)</a> concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15316973" 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 girl with features suggesting diastrophic dysplasia but with other features usually observed in Desbuquois dysplasia (<a href="/entry/251450">251450</a>), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), <a href="#20" class="mim-tip-reference" title="Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M. <strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong> Am. J. Med. Genet. 146A: 2920-2924, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925670</a>] [<a href="https://doi.org/10.1002/ajmg.a.32543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925670">Panzer et al. (2008)</a> identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation and a novel A133V mutation (<a href="#0014">606718.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 ACHONDROGENESIS, TYPE IB</strong>
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SLC26A2, ASN425ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893920 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893920;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=rs104893920" 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=rs104893920" 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=RCV000023569 OR RCV000055757 OR RCV001851641" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023569, RCV000055757, RCV001851641" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023569...</a>
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<p>In a patient with achondrogenesis type IB (ACG1B; <a href="/entry/600972">600972</a>), <a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> found compound heterozygosity for 2 structural mutations in the DTDST gene: a 1300A-G transition resulting in an asn425-to-asp (N425D) substitution in the ninth transmembrane domain, and a deletion of 1751A (<a href="#0001">606718.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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>.0007 ACHONDROGENESIS, TYPE IB</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> rs104893916 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893916;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/rs104893916?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=rs104893916" 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=rs104893916" 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=RCV000023570 OR RCV000055761 OR RCV000169017 OR RCV003234891" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023570, RCV000055761, RCV000169017, RCV003234891" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023570...</a>
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<p>In a fetus with achondrogenesis type IB (ACG1B; <a href="/entry/600972">600972</a>), <a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> identified a 2060G-T transversion in the SLC26A2 gene, resulting in a gly678-to-val (G678V) substitution in the cytoplasmic C terminus. The mutation was in compound heterozygosity with the R178X mutation (<a href="#0005">606718.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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 ACHONDROGENESIS, TYPE IB</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">rs121908077 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908077;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=rs121908077" 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=rs121908077" 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=RCV000023571 OR RCV000055756 OR RCV000355352 OR RCV000586327 OR RCV001004172 OR RCV001050109 OR RCV001810418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023571, RCV000055756, RCV000355352, RCV000586327, RCV001004172, RCV001050109, RCV001810418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023571...</a>
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<p><a href="#25" class="mim-tip-reference" title="Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R. <strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong> Nature Genet. 12: 100-102, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>] [<a href="https://doi.org/10.1038/ng0196-100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528239">Superti-Furga et al. (1996)</a> found homozygosity for deletion of val340 of the SLC26A2 gene in 2 patients with achondrogenesis type IB (ACG1B; <a href="/entry/600972">600972</a>). In 1 family, the parents were Turkish and consanguineous; in the other family, the parents were Hispanic and nonconsanguineous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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 Japanese male fetus with ACG1B, <a href="#3" class="mim-tip-reference" title="Cai, G., Nakayama, M., Hiraki, Y., Ozono, K. <strong>Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.</strong> Am. J. Med. Genet. 78: 58-60, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9637425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9637425</a>]" pmid="9637425">Cai et al. (1998)</a> identified homozygosity for deletion of val340. The mutation involves deletion of 1 of 3 GTT repeats at nucleotides 1039-1047. The GTT repeat may represent a deletion hotspot, thus explaining the occurrence of the deletion in different ethnic groups. The fetus was also homozygous for a thr689-to-ser (T689S) substitution. The T689S mutation appeared to be a polymorphism, as it was detected in 5 alleles of 26 healthy Japanese individuals. The T689S mutation was thought not to be pathologic because it was located in the C-terminal intracellular portion of the protein, involved amino acids with similar characteristics, and was found in homozygous state in 1 healthy Japanese individual. Both substitutions were found in heterozygous state in the 2 parents and a healthy brother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9637425" 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 DIASTROPHIC DYSPLASIA, BROAD BONE-PLATYSPONDYLIC VARIANT</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">rs104893921 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893921;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=rs104893921" 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=rs104893921" 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=RCV000004311 OR RCV000055758" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004311, RCV000055758" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004311...</a>
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<p><a href="#19" class="mim-tip-reference" title="Megarbane, A., Haddad, F. A., Haddad-Zebouni, S., Achram, M., Eich, G., Le Merrer, M., Superti-Furga, A. <strong>Homozygosity for a novel DTDST mutation in a child with a 'broad bone-platyspondylic' variant of diastrophic dysplasia.</strong> Clin. Genet. 56: 71-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466420</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560110.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10466420">Megarbane et al. (1999)</a> reported a 1-year-old Lebanese girl, born of second-cousin parents, who had clinical features suggesting diastrophic dysplasia (<a href="/entry/222600">222600</a>) but with unusual radiographic features, including severe platyspondyly, wide metaphyses, and fibular overgrowth, which were partially reminiscent of metatropic dysplasia (see <a href="/entry/156550">156550</a>). Molecular analysis of the DTD gene (SLC26A2) revealed homozygosity for a l1388A-C transversion in exon 2, leading to a gln454-to-pro (Q454P) substitution in the tenth transmembrane domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10466420" 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="#18" class="mim-tip-reference" title="Megarbane, A., Farkh, I., Haddad-Zebouni, S. <strong>How many phenotypes in the DTDST family chondrodysplasias? (Letter)</strong> Clin. Genet. 62: 189-190, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220459</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620214.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12220459">Megarbane et al. (2002)</a> reported an aborted female fetus, the third child in the Lebanese family, presenting with almost the same clinical features as those observed in the girl reported by <a href="#19" class="mim-tip-reference" title="Megarbane, A., Haddad, F. A., Haddad-Zebouni, S., Achram, M., Eich, G., Le Merrer, M., Superti-Furga, A. <strong>Homozygosity for a novel DTDST mutation in a child with a 'broad bone-platyspondylic' variant of diastrophic dysplasia.</strong> Clin. Genet. 56: 71-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466420</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560110.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10466420">Megarbane et al. (1999)</a>. As marked variability within a sibship had been previously reported (<a href="#12" class="mim-tip-reference" title="Horton, W. A., Rimoin, D. L., Lachman, R. S., Skovby, F., Hollister, D. W., Spranger, J., Scott, C. I., Hall, J. G. <strong>The phenotype variability of diastrophic dysplasia.</strong> J. Pediat. 93: 609-613, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/702237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">702237</a>] [<a href="https://doi.org/10.1016/s0022-3476(78)80896-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="702237">Horton et al., 1978</a>; <a href="#7" class="mim-tip-reference" title="Hall, B. D. <strong>Diastrophic dysplasia: extreme variability within a sibship.</strong> Am. J. Med. Genet. 63: 28-33, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723083</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<28::AID-AJMG8>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8723083">Hall, 1996</a>), this was thought to account for the first affected baby of the family. The birth of a second, identically affected sib, suggested that this represents a distinctive form of the DTDST chondrodysplasia that presents a clinical variant between a mild form of atelosteogenesis type II (<a href="/entry/256050">256050</a>) and a severe form of diastrophic dysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12220459+10466420+8723083+702237" 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> rs386833492 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386833492;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/rs386833492?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=rs386833492" 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=rs386833492" 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=RCV000004312 OR RCV000597319 OR RCV000724163 OR RCV000763135 OR RCV000779466 OR RCV000780711 OR RCV000991163 OR RCV001030744 OR RCV001030745" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004312, RCV000597319, RCV000724163, RCV000763135, RCV000779466, RCV000780711, RCV000991163, RCV001030744, RCV001030745" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004312...</a>
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<p><a href="#9" class="mim-tip-reference" title="Hastbacka, J., Kerrebrock, A., Mokkala, K., Clines, G., Lovett, M., Kaitila, I., de la Chapelle, A., Lander, E. S. <strong>Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).</strong> Europ. J. Hum. Genet. 7: 664-670, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482955</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482955">Hastbacka et al. (1999)</a> identified the founder mutation underlying the high frequency of diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>) in Finland: a GT-to-GC transition in the splice donor site of the previously undescribed 5-prime untranslated exon of the DTDST gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482955" 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 7 Finnish individuals with diastrophic dysplasia, <a href="#2" class="mim-tip-reference" title="Bonafe, L., Hastbacka, J., de la Chapelle, A., Campos-Xavier, A. B., Chiesa, C., Forlino, A., Superti-Furga, A., Rossi, A. <strong>A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. (Letter)</strong> J. Med. Genet. 45: 827-831, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18708426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18708426</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18708426[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/10.1136/jmg.2007.057158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18708426">Bonafe et al. (2008)</a> found compound heterozygosity for the common Finnish mutation, IVS1+2T-C, and the T512K mutation (<a href="#0013">606718.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18708426" 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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<strong>.0011 EPIPHYSEAL DYSPLASIA, MULTIPLE, 4</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> rs104893924 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893924;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/rs104893924?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=rs104893924" 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=rs104893924" 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=RCV000004313 OR RCV000055760 OR RCV000224702 OR RCV000409936 OR RCV000411019 OR RCV000477884 OR RCV000780712 OR RCV001030750 OR RCV001813733 OR RCV002276531" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004313, RCV000055760, RCV000224702, RCV000409936, RCV000411019, RCV000477884, RCV000780712, RCV001030750, RCV001813733, RCV002276531" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004313...</a>
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<p><a href="#17" class="mim-tip-reference" title="Makitie, O., Savarirayan, R., Bonafe, L., Robertson, S., Susic, M., Superti-Furga, A., Cole, W.G. <strong>Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.</strong> Am. J. Med. Genet. 122A: 187-192, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966518</a>] [<a href="https://doi.org/10.1002/ajmg.a.20282" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12966518">Makitie et al. (2003)</a> identified a homozygous cys653-to-ser (C653S) mutation in 3 patients with early childhood-onset hip dysplasia, recurrent patella dislocation, and normal stature (EDM4; <a href="/entry/226900">226900</a>). Abnormal patella ossification was characteristic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966518" 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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<strong>.0012 ATELOSTEOGENESIS, TYPE II</strong>
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</h4>
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SLC26A2, 1-BP DEL, 418C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200881 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200881;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=rs786200881" 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=rs786200881" 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=RCV000004304 OR RCV000409927 OR RCV000410549 OR RCV000411386 OR RCV001851639" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004304, RCV000409927, RCV000410549, RCV000411386, RCV001851639" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004304...</a>
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<p>For discussion of the 1-bp deletion of cytosine-418 in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; <a href="/entry/256050">256050</a>) by <a href="#22" class="mim-tip-reference" title="Rossi, A., van der Harten, H. J., Beemer, F. A., Kleijer, W. J., Gitzelmann, R., Steinmann, B., Superti-Furga, A. <strong>Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.</strong> Hum. Genet. 98: 657-661, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931695</a>] [<a href="https://doi.org/10.1007/s004390050279" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8931695">Rossi et al. (1996)</a>, see <a href="#0002">606718.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8931695" 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="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 DE LA CHAPELLE DYSPLASIA</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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DIASTROPHIC DYSPLASIA, INCLUDED
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SLC26A2, THR512LYS
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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> rs121908078 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908078;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/rs121908078?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=rs121908078" 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=rs121908078" 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=RCV000004314 OR RCV000004315 OR RCV002512749 OR RCV004700186" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004314, RCV000004315, RCV002512749, RCV004700186" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004314...</a>
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<p>In affected members of the original family with de la Chapelle dysplasia (DLCD; see <a href="/entry/256050">256050</a>) (<a href="#5" class="mim-tip-reference" title="de la Chapelle, A., Maroteaux, P., Havu, N., Granroth, G. <strong>Une rare dysplasie osseuse letale de transmission recessive autosomique.</strong> Arch. Franc. Pediat. 29: 759-770, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4644462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4644462</a>]" pmid="4644462">de la Chapelle et al., 1972</a>), <a href="#2" class="mim-tip-reference" title="Bonafe, L., Hastbacka, J., de la Chapelle, A., Campos-Xavier, A. B., Chiesa, C., Forlino, A., Superti-Furga, A., Rossi, A. <strong>A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. (Letter)</strong> J. Med. Genet. 45: 827-831, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18708426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18708426</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18708426[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/10.1136/jmg.2007.057158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18708426">Bonafe et al. (2008)</a> identified a homozygous 1535C-A transversion in the SLC26A2 gene, resulting in a thr512-to-lys (T512K) substitution in the sixth cytoplasmic domain. In 7 Finnish individuals with diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>), <a href="#2" class="mim-tip-reference" title="Bonafe, L., Hastbacka, J., de la Chapelle, A., Campos-Xavier, A. B., Chiesa, C., Forlino, A., Superti-Furga, A., Rossi, A. <strong>A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. (Letter)</strong> J. Med. Genet. 45: 827-831, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18708426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18708426</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18708426[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/10.1136/jmg.2007.057158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18708426">Bonafe et al. (2008)</a> found compound heterozygosity for the T512K mutation and the common Finnish mutation (<a href="#0010">606718.0010</a>). In vitro functional expression studies in Chinese hamster ovary cells showed that the T512K-mutant protein had no sulfate uptake. The T512K mutation was not identified in 200 unrelated Finnish controls and 150 non-Finnish Caucasian controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4644462+18708426" 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="0014" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0014 DIASTROPHIC DYSPLASIA</strong>
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</span>
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</h4>
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SLC26A2, ALA133VAL
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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> rs267607055 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607055;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/rs267607055?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=rs267607055" 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=rs267607055" 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=RCV000004316 OR RCV004526589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004316, RCV004526589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004316...</a>
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<p>In a girl with features suggesting diastrophic dysplasia (DTD; <a href="/entry/222600">222600</a>) but with other features usually observed in Desbuquois dysplasia (<a href="/entry/251450">251450</a>), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), <a href="#20" class="mim-tip-reference" title="Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M. <strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong> Am. J. Med. Genet. 146A: 2920-2924, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925670</a>] [<a href="https://doi.org/10.1002/ajmg.a.32543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925670">Panzer et al. (2008)</a> identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation (<a href="#0005">606718.0005</a>) and a novel A133V mutation. <a href="#20" class="mim-tip-reference" title="Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M. <strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong> Am. J. Med. Genet. 146A: 2920-2924, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925670</a>] [<a href="https://doi.org/10.1002/ajmg.a.32543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925670">Panzer et al. (2008)</a> noted that the A133V mutation occurs at a boundary between one of the transmembrane and extracellular regions and that the changed amino acid remains hydrophobic and fairly small. They suggested that the A133V substitution is likely to create only a subtle effect on the functionality of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925670" 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="0015" class="mim-anchor"></a>
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<strong>.0015 EPIPHYSEAL DYSPLASIA, MULTIPLE, 4</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">rs1561822760 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1561822760;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=rs1561822760" 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=rs1561822760" 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=RCV000761587" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000761587" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000761587</a>
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<p>For discussion of the c.1565C-T transition (c.1565C-T, NM_00112.3) in the SLC26A2 gene, resulting in a ser522-to-phe (S522F) substitution, that was found in compound heterozygous state in a patient with multiple epiphyseal dysplasia-4 (EDM4; <a href="/entry/226900">226900</a>) by <a href="#1" class="mim-tip-reference" title="Barreda-Bonis, A. C., Barraza-Garcia, J., Parron, M., Pastor, I., Heath, K. E., Gonzalez-Casado, I. <strong>Multiple SLC26A2 mutations occurring in a three-generational family.</strong> Europ. J. Med. Genet. 61: 24-28, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29024831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29024831</a>] [<a href="https://doi.org/10.1016/j.ejmg.2017.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29024831">Barreda-Bonis et al. (2018)</a>, see <a href="#0002">606718.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29024831" 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="Barreda-Bonis2018" class="mim-anchor"></a>
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Barreda-Bonis, A. C., Barraza-Garcia, J., Parron, M., Pastor, I., Heath, K. E., Gonzalez-Casado, I.
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<strong>Multiple SLC26A2 mutations occurring in a three-generational family.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29024831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29024831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29024831" 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.ejmg.2017.10.007" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2007.057158" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11565064[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=11565064" 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/10.1086/324023" target="_blank">Full Text</a>]
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Forlino, A., Piazza, R., Tiveron, C., Della Torre, S., Tatangelo, L., Bonafe, L., Gualeni, B., Romano, A., Pecora, F., Superti-Furga, A., Cetta, G., Rossi, A.
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<strong>A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.</strong>
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[<a href="https://doi.org/10.1093/hmg/ddi079" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<28::AID-AJMG8>3.0.CO;2-O" target="_blank">Full Text</a>]
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Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S.
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[<a href="https://doi.org/10.1016/0092-8674(94)90281-x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200361" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(78)80896-8" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.38.3.191" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/10.14.1485" target="_blank">Full Text</a>]
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Karniski, L. P.
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<strong>Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.</strong>
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Hum. Molec. Genet. 13: 2165-2171, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15294877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15294877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15294877" 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/ddh242" target="_blank">Full Text</a>]
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Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P.
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<strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong>
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Am. J. Med. Genet. 129A: 190-192, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15316973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15316973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15316973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30149" target="_blank">Full Text</a>]
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Makitie, O., Savarirayan, R., Bonafe, L., Robertson, S., Susic, M., Superti-Furga, A., Cole, W.G.
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<strong>Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.</strong>
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Am. J. Med. Genet. 122A: 187-192, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20282" target="_blank">Full Text</a>]
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Megarbane, A., Farkh, I., Haddad-Zebouni, S.
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<strong>How many phenotypes in the DTDST family chondrodysplasias? (Letter)</strong>
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Clin. Genet. 62: 189-190, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220459" 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/10.1034/j.1399-0004.2002.620214.x" target="_blank">Full Text</a>]
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Megarbane, A., Haddad, F. A., Haddad-Zebouni, S., Achram, M., Eich, G., Le Merrer, M., Superti-Furga, A.
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<strong>Homozygosity for a novel DTDST mutation in a child with a 'broad bone-platyspondylic' variant of diastrophic dysplasia.</strong>
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Clin. Genet. 56: 71-76, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10466420" 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/10.1034/j.1399-0004.1999.560110.x" target="_blank">Full Text</a>]
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Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M.
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<strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong>
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Am. J. Med. Genet. 146A: 2920-2924, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32543" target="_blank">Full Text</a>]
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Rossi, A., Superti-Furga, A.
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<strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance.</strong>
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Hum. Mutat. 17: 159-171, 2001. Note: Erratum: Hum. Mutat. 18: 82 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241838" 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.1" target="_blank">Full Text</a>]
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Rossi, A., van der Harten, H. J., Beemer, F. A., Kleijer, W. J., Gitzelmann, R., Steinmann, B., Superti-Furga, A.
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<strong>Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.</strong>
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Hum. Genet. 98: 657-661, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8931695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004390050279" target="_blank">Full Text</a>]
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<a id="Satoh1998" class="mim-anchor"></a>
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Satoh, H., Susaki, M., Shukunami, C., Iyama, K., Negoro, T., Hiraki, Y.
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<strong>Functional analysis of diastrophic dysplasia sulfate transporter: its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.</strong>
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J. Biol. Chem. 273: 12307-12315, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9575183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9575183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9575183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.273.20.12307" target="_blank">Full Text</a>]
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Superti-Furga, A., Hastbacka, J., Cohn, D. H., Wilcox, W., van der Harten, H. J., Rimoin, D. L., Lander, E. S., Steinmann, B., Gitzelmann, R.
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<strong>Defective sulfation of proteoglycans in achondrogenesis type 1B is caused by mutations in the DTDST gene: the disorder is allelic to diastrophic dysplasia. (Abstract)</strong>
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Am. J. Hum. Genet. 57: A48, 1995.
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Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R.
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<strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong>
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Nature Genet. 12: 100-102, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528239" 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/ng0196-100" target="_blank">Full Text</a>]
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Superti-Furga, A., Neumann, L., Riebel, T., Eich, G., Steinmann, B., Spranger, J., Kunze, J.
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<strong>Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.</strong>
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J. Med. Genet. 36: 621-624, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10465113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10465113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10465113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Superti-Furga, A., Rossi, A., Steinmann, B., Gitzelmann, R.
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<strong>A chondrodysplasia family produced by mutations in the diastrophic dysplasia sulfate transporter gene: genotype/phenotype correlations.</strong>
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Am. J. Med. Genet. 63: 144-147, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723100</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723100" 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/(SICI)1096-8628(19960503)63:1<144::AID-AJMG25>3.0.CO;2-N" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 03/22/2019
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Nara Sobreira - updated : 3/26/2010<br>Cassandra L. Kniffin - updated : 2/11/2009<br>George E. Tiller - updated : 4/25/2008<br>George E. Tiller - updated : 4/5/2007<br>Marla J. F. O'Neill - updated : 10/25/2006<br>Marla J. F. O'Neill - updated : 10/13/2006<br>Marla J. F. O'Neill - updated : 10/7/2004<br>Felicity Collins - updated : 12/5/2003<br>Victor A. McKusick - updated : 11/20/2002<br>Michael J. Wright - updated : 6/28/2002
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Ada Hamosh : 2/25/2002
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carol : 03/22/2019
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carol : 04/06/2015<br>mcolton : 3/30/2015<br>carol : 5/8/2014<br>carol : 12/12/2012<br>terry : 1/27/2012<br>terry : 11/3/2010<br>carol : 3/29/2010<br>terry : 3/26/2010<br>wwang : 4/20/2009<br>wwang : 4/6/2009<br>ckniffin : 2/11/2009<br>carol : 2/3/2009<br>wwang : 4/30/2008<br>terry : 4/25/2008<br>alopez : 4/10/2007<br>terry : 4/5/2007<br>carol : 10/26/2006<br>carol : 10/25/2006<br>terry : 10/13/2006<br>carol : 10/11/2004<br>carol : 10/11/2004<br>terry : 10/7/2004<br>carol : 12/10/2003<br>carol : 12/5/2003<br>cwells : 11/26/2002<br>terry : 11/20/2002<br>alopez : 6/28/2002<br>carol : 3/8/2002<br>terry : 3/8/2002<br>carol : 2/28/2002<br>carol : 2/27/2002<br>terry : 2/27/2002<br>terry : 2/27/2002<br>carol : 2/25/2002
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SOLUTE CARRIER FAMILY 26 (SULFATE TRANSPORTER), MEMBER 2; SLC26A2
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DTD SULFATE TRANSPORTER; DTDST
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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: SLC26A2</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> 14870002, 254055004, 58561002, 715672007;
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<strong>ICD10CM:</strong> Q77.5;
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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: 5q32
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:149,960,758-149,987,400 </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">
|
|
<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
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>
|
|
Inheritance
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
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|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
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<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
5q32
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|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Achondrogenesis Ib
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600972
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Atelosteogenesis, type II
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256050
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
De la Chapelle dysplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256050
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diastrophic dysplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
222600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diastrophic dysplasia, broad bone-platyspondylic variant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
222600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epiphyseal dysplasia, multiple, 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
226900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
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|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Hastbacka et al. (1994) reported the positional cloning of the gene mutated in diastrophic dysplasia (DTD; 222600) by fine-structure linkage disequilibrium mapping. The gene was found to encode a novel sulfate transporter, and was thus symbolized DTDST. Impaired function of DTDST product would be expected to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause a clinical phenotype such as diastrophic dysplasia. A defect in sulfate transport was demonstrable in fibroblasts from a DTD patient. The full transcript was expected to be 8.4 kb. </p><p>Satoh et al. (1998) cloned a rat osteoblastic cell DTDST cDNA encoding a 739-amino acid protein that is 73% identical to the human coding sequence. Northern blot analysis suggested that expression is predominantly in cartilage and intestine. The rat gene contains at least 5 exons. Injection of rat and human DTDST cRNA into frog oocytes induces Na(+)-independent sulfate transport that can be inhibited by extracellular chloride and bicarbonate. Satoh et al. (1998) observed a similar activity profile in chondrocytes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By positional cloning, Hastbacka et al. (1994) mapped the DTDST gene approximately 70 kb proximal to CSF1R on 5q32-q33.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hastbacka et al. (1994) identified point mutations in non-Finnish patients with DTD. Three patients from 3 different countries, Germany, the Netherlands, and France, were found to be heterozygous for a single base deletion in codon 575 (AAG to AG; 606718.0001). An American patient was found to have a 3-prime splice acceptor site mutation from AG to AC in heterozygous state. A third mutation, found in a Canadian patient, involved a deletion of 1 nucleotide in codon 661 (ACA to AC). This deletion was predicted to lead to a premature translational stop after 5 codons with truncation of the last 10% of the protein, including half of the highly conserved region in the C-terminal cytoplasmic tail. </p><p>Superti-Furga et al. (1995, 1996) described mutations in the DTDST gene (see 606718.0001 and 606718.0005-606718.0008) in patients with achondrogenesis type IB (600972). Hastbacka et al. (1995, 1996) identified mutations in the DTDST gene (see 606718.0001-606718.0004) in atelosteogenesis type II (256050). Thus, both of these disorders are allelic to diastrophic dysplasia. </p><p>Hastbacka et al. (1999) reported identification of a Finnish DTD founder mutation, a GT-to-GC transition in the splice donor site of the previously undescribed 5-prime untranslated exon of the DTDST gene (606718.0010). The mutation acts by severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried 2 copies of the mutation in 69 families, 1 copy in 14 families, and no copies in 1 family. Thus, roughly 90% of the Finnish DTD chromosomes carried the splice site mutation, which Hastbacka et al. (1999) designated DTDST(Fin). Unexpectedly, they found that 9 of the DTD chromosomes having the apparently ancestral haplotype did not carry the Finnish mutation but rather 2 other mutations. Eight of these chromosomes had an R279W mutation (606718.0002) and 1 had a V340 deletion (606718.0008). One possible explanation was that the 3 DTD mutations arose in a population in which this 'rare' haplotype was in fact common and conferred a heterozygote advantage in this population, resulting in an excess of DTD mutations on this haplotype which were then admixed with a larger population in which the haplotype was rare. There was, however, no evidence to support the existence of such an ancestral population or of a heterozygote advantage conferred by DTD chromosomes. A second possibility was that the chromosomes with the rare haplotype are more prone to mutation, although again there was no evidence to support such a hypothesis. Finally, a third possibility was, of course, that the presence of multiple mutations on a rare haplotype are simply a matter of chance. </p><p>Karniski (2001) compared the sulfate transport activity of 11 reported DTDST mutations upon expression in Xenopus oocytes. Five mutations, including G255E (606718.0003), delta-A1751 (606718.0001), R178X (606718.0005), and N425D (606718.0006) exhibited minimal sulfate transport function. Two mutations, delta-V340 (606718.0008) and R279W (606718.0002), transported sulfate at rates of 17% and 32%, respectively, of wildtype DTDST. Four mutations, including A715V (606718.0004), Q454P (606718.0009), and G678V (606718.0007), had rates of sulfate transport nearly equal to that of wildtype DTDST. In the Xenopus oocyte expression system, the correlation between residual transport function and the severity of human phenotype was not absolute, suggesting that factors in addition to the intrinsic sulfate transport properties of the DTDST protein may influence the phenotype in individuals with DTDST mutations. </p><p>Rossi and Superti-Furga (2001) stated that over 30 mutations in the SLC26A2 gene had been observed, including 22 novel mutations that they reported. </p><p>Karniski (2004) expressed DTDST-mediated sulfate transport in human embryonic kidney (HEK) cells and determined that the wildtype protein was glycosylated and localized to the cell plasma membrane. Four mutations, R279W (606718.0002), A715V (606718.0004), Q454P (606718.0009), and C653S (606718.0011), stimulated sulfate transport at rates only 39 to 62% of wildtype DTDST and were properly localized, but were underexpressed compared to wildtype DTDST. The Q454P mutant was unique in that it was not properly glycosylated in HEK cells, and the G678V (606718.0007) mutant was trapped within the cytoplasm. There was no difference in sulfate transport activity between cells transfected with either the delta-V340 or the G678V mutations and control HEK cells. Individuals with severe achondrogenesis 1B phenotype had null mutations on both DTDST alleles. Heterozygotes for both a null mutation and a partial-function mutation exhibited either atelosteogenesis type 2 or DTD, whereas those homozygous for partial-function mutations exhibited the milder, recessive multiple epiphyseal dysplasia phenotype. In contrast to previous studies in Xenopus laevis oocytes (Karniski, 2001), there was a strong correlation between the severity of the phenotype and the level of residual transport function in mammalian cells. </p><p>In affected members of the original family with de la Chapelle dysplasia (DLCD; see 256050 and de la Chapelle et al., 1972), Bonafe et al. (2008) identified a homozygous mutation in the SLC26A2 gene (606718.0013). The findings confirmed that de la Chapelle dysplasia is allelic to other SLC26A2 disorders. </p><p>Using a targeted next-generation sequencing skeletal dysplasia panel, Barreda-Bonis et al. (2018) identified mutations in the SLC26A2 gene in a 14-year-old-girl and her maternal grandfather with EDM4. The girl was compound heterozygous for the common R279W mutation (606718.0002), inherited from her mother, and a S522F mutation (606718.0015), inherited from her father. Her grandfather was homozygous for the R279W mutation. The girl's mother was short (-3.53 SD), but was only a carrier of the R279W mutation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Comparing the severity of ACG IB to that of DTD, Superti-Furga et al. (1996) noted that ACG IB patients appeared to have structural DTDST mutations on both chromosomes, whereas no DTD patient had been found to that time with 2 structural mutations in DTDST. Rather, there appeared to be a DTD-specific allele, present at a frequency approaching 1% in the Finnish population, having an intact coding region. This allele gives no detectable mRNA by Northern blot analysis, or at the most a very small amount. They noted that the 1751A deletion mutation (606718.0001) results in diastrophic dysplasia when compounded with the presumed reduced-expression allele frequent in Finland (606718.0010), but produces ACG IB when compounded with a second structural mutation on the other chromosome, such as N425D (606718.0006). </p><p>Superti-Furga et al. (1996) reviewed the 3 recessively inherited chondrodysplasias of decreasing severity caused by mutations in the DTDST gene: diastrophic dysplasia, atelosteogenesis type II, and achondrogenesis type IB. Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory mutations usually result in one of the less severe phenotypes. The chondrodysplasias arising at the DTDST locus all have recessive inheritance. </p><p>In a Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II, Macias-Gomez et al. (2004) identified compound heterozygosity for the R279W and R178X (606718.0005) mutations in the SLC26A2 gene. Macias-Gomez et al. (2004) concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. </p><p>In a girl with features suggesting diastrophic dysplasia but with other features usually observed in Desbuquois dysplasia (see 251450), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), Panzer et al. (2008) identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation and a novel A133V mutation (606718.0014). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Forlino et al. (2005) generated Slc26a2-knockin mice with a partial loss of function of the sulfate transporter resulting from abnormal splicing. Homozygous mutant mice were characterized by growth retardation, skeletal dysplasia and joint contractures, recapitulating essential aspects of the human DTD phenotype. The skeletal phenotype included reduced toluidine blue staining of cartilage, chondrocytes of irregular size, delay in the formation of the secondary ossification center and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts. In spite of the generalized nature of the sulfate uptake defect, significant proteoglycan undersulfation was detected only in cartilage. Chondrocyte proliferation and apoptosis studies suggested that reduced proliferation and/or lack of terminal chondrocyte differentiation might contribute to reduced bone growth. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>15 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DIASTROPHIC DYSPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
ACHONDROGENESIS, TYPE IB, INCLUDED<br />
|
|
ATELOSTEOGENESIS, TYPE II, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A2, 1-BP DEL, 1751A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs386833498,
|
|
|
|
|
|
gnomAD: rs386833498,
|
|
|
|
|
|
ClinVar: RCV000004302, RCV000004303, RCV000023567, RCV000586135, RCV000817526, RCV002276529
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 patients with diastrophic dysplasia (DTD; 222600) from Germany, the Netherlands, and France, respectively, Hastbacka et al. (1994) identified heterozygosity for a deletion of 1 nucleotide in codon 575 of the DTD gene (SLC26A2), converting AAG to AG; this mutation resulted in a frameshift, causing a premature translational stop after 9 codons that would eliminate the last 20% of the protein. The deletion destroyed a DdeI site and created a BfaI site, providing a simple assay for the presence of the mutation. The patients presumably carried a different DTD mutation on the other homolog. Examination of 100 normal chromosomes confirmed that the deletion was not a polymorphism. </p><p>Superti-Furga et al. (1996) found that this mutation, which they called the 1751A deletion, results in diastrophic dysplasia when compounded with the presumed reduced-expression allele frequent in Finland (606718.0010), but produces achondrogenesis type IB (ACG1B; 600972) when compounded with a second structural mutation on the other chromosome, such as N425D (606718.0006). </p><p>In a patient with atelosteogenesis type II (AO2; 256050), Hastbacka et al. (1996) identified compound heterozygosity for 1751delA and an 862C-T transition resulting in an R279W substitution (606718.0002) in the third extracellular loop. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ATELOSTEOGENESIS, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DIASTROPHIC DYSPLASIA, INCLUDED<br />
|
|
EPIPHYSEAL DYSPLASIA, MULTIPLE, 4, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A2, ARG279TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893915,
|
|
|
|
|
|
gnomAD: rs104893915,
|
|
|
|
|
|
ClinVar: RCV000004305, RCV000004306, RCV000004307, RCV000266165, RCV000275762, RCV000586600, RCV000624686, RCV000641290, RCV000999764, RCV001030752, RCV001030753, RCV002276530
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
|
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<p><strong><em>Atelosteogeneis Type II and Diastrophic Dysplasia</em></strong></p><p>
|
|
For discussion of the arg279-to-trp (R279W) mutation in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; 256050) by Hastbacka et al. (1996), see 606718.0001. </p><p>Hastbacka et al. (1996) also found the R279W substitution in compound heterozygous state in 4 patients with diastrophic dysplasia (DTD; 222600). </p><p>Rossi et al. (1996) studied fibroblast cultures of 3 new patients with mutations in the DTDST gene: one with diastrophic dysplasia (the least severe of the conditions caused by DTDST mutations), one with the more severe atelosteogenesis type II, and one with an intermediate phenotype designated AO2/DTD. Reduced incorporation of inorganic sulfate into macromolecules was found in all 3. Each of the 3 patients was found to be heterozygous for R279W. In 2 patients (DTD and OA2/DTD), no other structural mutation was found, but PCR amplification and SSCP analysis of fibroblast cDNA showed reduced mRNA levels of the wildtype DTDST allele. Rossi et al. (1996) stated that these 2 patients may be compound heterozygotes for the 'Finnish' mutation which had as yet not been characterized at the DNA level and which was known to cause reduced expression of DTDST. The third patient (with AO2) had the R279W mutation compounded with a novel mutation, the deletion of cytosine-418 (606718.0012), predicting a frameshift with premature termination. This allele was underrepresented in the cDNA, in accordance with previous observations that premature stop codons reduce mRNA levels. The presence of the DTDST R297W mutation in a total of 11 patients with AO2 or DTD emphasized the overlap between these conditions. This mutation was not found in 8 analyzed patients with achondrogenesis type IB (ACG IB), the clinically most severe member of this family of chondrodysplasias, suggesting that the R279W mutation allows some residual activity of the sulfate transporter. </p><p>In a Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II, Macias-Gomez et al. (2004) identified compound heterozygosity for the R279W and R178X (606718.0005) mutations in the SLC26A2 gene. Macias-Gomez et al. (2004) concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. </p><p><strong><em>Multiple Epiphyseal Dysplasia 4</em></strong></p><p>
|
|
Superti-Furga et al. (1999) reported a 36-year-old man with a recessively inherited form of multiple epiphyseal dysplasia (EDM4; 226900) characterized by tall-normal stature, clubfoot, and an unusual double-layered patella. This man was found to have a homozygous R279W mutation in the DTDST gene product. Both healthy parents were heterozygous for this mutation. Analysis of the proband's fibroblasts showed a sulfate incorporation defect typical of disorders caused by DTDST mutations. </p><p>Huber et al. (2001) found the R279W mutation in homozygosity in affected members of 2 unrelated sibships with multiple epiphyseal dysplasia, who were initially thought to have isolated clubfoot. </p><p>Czarny-Ratajczak et al. (2001) identified the homozygous R279W mutation in 2 probands with multiple epiphyseal dysplasia and multipartite patella (see 226900). </p><p>Using a targeted next-generation sequencing skeletal dysplasia panel, Barreda-Bonis et al. (2018) identified mutations in the SLC26A2 gene in a 14-year-old girl and her maternal grandfather with EDM4. The girl was compound heterozygous for the R279W mutation, inherited from her mother, and a c.1565C-T transition, resulting in a ser522-to-phe (S522F; 606718.0015) substitution, inherited from her father. Her grandfather was homozygous for the R279W mutation. The girl's mother was short (-3.53 SD), but was only a carrier for the R279W mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ATELOSTEOGENESIS, TYPE II</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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SLC26A2, GLY255GLU
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<br />
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SNP: rs104893917,
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gnomAD: rs104893917,
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ClinVar: RCV000004308, RCV000675076, RCV001851640, RCV003230347
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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>Patient 3 with atelosteogenesis type II (AO2; 256050) investigated by Hastbacka et al. (1996) was a compound heterozygote for a 791G-A transition in the SLC26A2 gene, leading to a G255E substitution that introduced a negative charge in the highly conserved fifth putative transmembrane domain of the protein, and a 2171C-T transition, leading to an A715V substitution (606718.0004) close to the C terminus of the protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 ATELOSTEOGENESIS, TYPE II</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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SLC26A2, ALA715VAL
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<br />
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SNP: rs104893918,
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gnomAD: rs104893918,
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ClinVar: RCV000004309, RCV000675095, RCV000797878, RCV003472968
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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>For discussion of the ala715-to-val (A715V) mutation in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; 256050) by Hastbacka et al. (1996), see 606718.0003. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 ACHONDROGENESIS, TYPE IB</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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DIASTROPHIC DYSPLASIA, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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SLC26A2, ARG178TER
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<br />
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SNP: rs104893919,
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gnomAD: rs104893919,
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ClinVar: RCV000004310, RCV000023568, RCV000175526, RCV000411745, RCV000412934, RCV000590163, RCV000690242, RCV000779467, RCV001030754
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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 3 patients with achondrogenesis type IB (ACG1B; 600972), Superti-Furga et al. (1996) found compound heterozygosity for a 559C-T transition in the SLC26A2 gene, resulting in an R178X amino substitution. The nonsense mutation resulted in truncation of approximately 75% of the protein. In each of the 3 cases the other mutant allele was a structural mutation (see, e.g., 606718.0007). </p><p>In a Mexican girl with diastrophic dysplasia (DTD; 222600) presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II (AO2; 256050), Macias-Gomez et al. (2004) identified compound heterozygosity for the R279W (606718.0002) and R178X mutations in the SLC26A2 gene; see 606718.0002. Macias-Gomez et al. (2004) concluded that the combination of a mild and a severe mutation led to an intermediate clinical picture, representing an apparent genotype-phenotype correlation. </p><p>In a girl with features suggesting diastrophic dysplasia but with other features usually observed in Desbuquois dysplasia (251450), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), Panzer et al. (2008) identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation and a novel A133V mutation (606718.0014). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 ACHONDROGENESIS, TYPE IB</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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SLC26A2, ASN425ASP
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<br />
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SNP: rs104893920,
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ClinVar: RCV000023569, RCV000055757, RCV001851641
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with achondrogenesis type IB (ACG1B; 600972), Superti-Furga et al. (1996) found compound heterozygosity for 2 structural mutations in the DTDST gene: a 1300A-G transition resulting in an asn425-to-asp (N425D) substitution in the ninth transmembrane domain, and a deletion of 1751A (606718.0001). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 ACHONDROGENESIS, TYPE IB</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
SLC26A2, GLY678VAL
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<br />
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|
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SNP: rs104893916,
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|
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gnomAD: rs104893916,
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|
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ClinVar: RCV000023570, RCV000055761, RCV000169017, RCV003234891
|
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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 fetus with achondrogenesis type IB (ACG1B; 600972), Superti-Furga et al. (1996) identified a 2060G-T transversion in the SLC26A2 gene, resulting in a gly678-to-val (G678V) substitution in the cytoplasmic C terminus. The mutation was in compound heterozygosity with the R178X mutation (606718.0005). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ACHONDROGENESIS, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A2, VAL340DEL
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|
<br />
|
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|
|
SNP: rs121908077,
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|
|
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|
|
|
|
ClinVar: RCV000023571, RCV000055756, RCV000355352, RCV000586327, RCV001004172, RCV001050109, RCV001810418
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Superti-Furga et al. (1996) found homozygosity for deletion of val340 of the SLC26A2 gene in 2 patients with achondrogenesis type IB (ACG1B; 600972). In 1 family, the parents were Turkish and consanguineous; in the other family, the parents were Hispanic and nonconsanguineous. </p><p>In a Japanese male fetus with ACG1B, Cai et al. (1998) identified homozygosity for deletion of val340. The mutation involves deletion of 1 of 3 GTT repeats at nucleotides 1039-1047. The GTT repeat may represent a deletion hotspot, thus explaining the occurrence of the deletion in different ethnic groups. The fetus was also homozygous for a thr689-to-ser (T689S) substitution. The T689S mutation appeared to be a polymorphism, as it was detected in 5 alleles of 26 healthy Japanese individuals. The T689S mutation was thought not to be pathologic because it was located in the C-terminal intracellular portion of the protein, involved amino acids with similar characteristics, and was found in homozygous state in 1 healthy Japanese individual. Both substitutions were found in heterozygous state in the 2 parents and a healthy brother. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DIASTROPHIC DYSPLASIA, BROAD BONE-PLATYSPONDYLIC VARIANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A2, GLN454PRO
|
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|
|
<br />
|
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|
|
SNP: rs104893921,
|
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|
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|
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ClinVar: RCV000004311, RCV000055758
|
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|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Megarbane et al. (1999) reported a 1-year-old Lebanese girl, born of second-cousin parents, who had clinical features suggesting diastrophic dysplasia (222600) but with unusual radiographic features, including severe platyspondyly, wide metaphyses, and fibular overgrowth, which were partially reminiscent of metatropic dysplasia (see 156550). Molecular analysis of the DTD gene (SLC26A2) revealed homozygosity for a l1388A-C transversion in exon 2, leading to a gln454-to-pro (Q454P) substitution in the tenth transmembrane domain. </p><p>Megarbane et al. (2002) reported an aborted female fetus, the third child in the Lebanese family, presenting with almost the same clinical features as those observed in the girl reported by Megarbane et al. (1999). As marked variability within a sibship had been previously reported (Horton et al., 1978; Hall, 1996), this was thought to account for the first affected baby of the family. The birth of a second, identically affected sib, suggested that this represents a distinctive form of the DTDST chondrodysplasia that presents a clinical variant between a mild form of atelosteogenesis type II (256050) and a severe form of diastrophic dysplasia. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DIASTROPHIC DYSPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A2, IVS1DS, T-C, +2
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs386833492,
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|
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|
|
|
gnomAD: rs386833492,
|
|
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|
|
|
ClinVar: RCV000004312, RCV000597319, RCV000724163, RCV000763135, RCV000779466, RCV000780711, RCV000991163, RCV001030744, RCV001030745
|
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|
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|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Hastbacka et al. (1999) identified the founder mutation underlying the high frequency of diastrophic dysplasia (DTD; 222600) in Finland: a GT-to-GC transition in the splice donor site of the previously undescribed 5-prime untranslated exon of the DTDST gene. </p><p>In 7 Finnish individuals with diastrophic dysplasia, Bonafe et al. (2008) found compound heterozygosity for the common Finnish mutation, IVS1+2T-C, and the T512K mutation (606718.0013). </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EPIPHYSEAL DYSPLASIA, MULTIPLE, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
SLC26A2, CYS653SER
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<br />
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SNP: rs104893924,
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|
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gnomAD: rs104893924,
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|
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ClinVar: RCV000004313, RCV000055760, RCV000224702, RCV000409936, RCV000411019, RCV000477884, RCV000780712, RCV001030750, RCV001813733, RCV002276531
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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>Makitie et al. (2003) identified a homozygous cys653-to-ser (C653S) mutation in 3 patients with early childhood-onset hip dysplasia, recurrent patella dislocation, and normal stature (EDM4; 226900). Abnormal patella ossification was characteristic. </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>.0012 ATELOSTEOGENESIS, TYPE II</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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|
SLC26A2, 1-BP DEL, 418C
|
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<br />
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|
|
SNP: rs786200881,
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|
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ClinVar: RCV000004304, RCV000409927, RCV000410549, RCV000411386, RCV001851639
|
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|
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</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion of cytosine-418 in the SLC26A2 gene that was found in compound heterozygous state in a patient with atelosteogenesis type II (AO2; 256050) by Rossi et al. (1996), see 606718.0002. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<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>.0013 DE LA CHAPELLE DYSPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DIASTROPHIC DYSPLASIA, 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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SLC26A2, THR512LYS
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<br />
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SNP: rs121908078,
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gnomAD: rs121908078,
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ClinVar: RCV000004314, RCV000004315, RCV002512749, RCV004700186
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of the original family with de la Chapelle dysplasia (DLCD; see 256050) (de la Chapelle et al., 1972), Bonafe et al. (2008) identified a homozygous 1535C-A transversion in the SLC26A2 gene, resulting in a thr512-to-lys (T512K) substitution in the sixth cytoplasmic domain. In 7 Finnish individuals with diastrophic dysplasia (DTD; 222600), Bonafe et al. (2008) found compound heterozygosity for the T512K mutation and the common Finnish mutation (606718.0010). In vitro functional expression studies in Chinese hamster ovary cells showed that the T512K-mutant protein had no sulfate uptake. The T512K mutation was not identified in 200 unrelated Finnish controls and 150 non-Finnish Caucasian controls. </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>.0014 DIASTROPHIC DYSPLASIA</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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SLC26A2, ALA133VAL
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<br />
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SNP: rs267607055,
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gnomAD: rs267607055,
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ClinVar: RCV000004316, RCV004526589
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a girl with features suggesting diastrophic dysplasia (DTD; 222600) but with other features usually observed in Desbuquois dysplasia (251450), such as neonatal scoliosis, flat acetabular roof, and proximal femur monkey wrench configuration (which was present in early but not later radiographs), Panzer et al. (2008) identified compound heterozygosity for mutations in the SLC26A2 gene: the common R178X mutation (606718.0005) and a novel A133V mutation. Panzer et al. (2008) noted that the A133V mutation occurs at a boundary between one of the transmembrane and extracellular regions and that the changed amino acid remains hydrophobic and fairly small. They suggested that the A133V substitution is likely to create only a subtle effect on the functionality of the protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0015 EPIPHYSEAL DYSPLASIA, MULTIPLE, 4</strong>
|
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</span>
|
|
</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SLC26A2, SER522PHE
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<br />
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SNP: rs1561822760,
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|
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ClinVar: RCV000761587
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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>For discussion of the c.1565C-T transition (c.1565C-T, NM_00112.3) in the SLC26A2 gene, resulting in a ser522-to-phe (S522F) substitution, that was found in compound heterozygous state in a patient with multiple epiphyseal dysplasia-4 (EDM4; 226900) by Barreda-Bonis et al. (2018), see 606718.0002. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Barreda-Bonis, A. C., Barraza-Garcia, J., Parron, M., Pastor, I., Heath, K. E., Gonzalez-Casado, I.
|
|
<strong>Multiple SLC26A2 mutations occurring in a three-generational family.</strong>
|
|
Europ. J. Med. Genet. 61: 24-28, 2018.
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|
[PubMed: 29024831]
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[Full Text: https://doi.org/10.1016/j.ejmg.2017.10.007]
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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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Bonafe, L., Hastbacka, J., de la Chapelle, A., Campos-Xavier, A. B., Chiesa, C., Forlino, A., Superti-Furga, A., Rossi, A.
|
|
<strong>A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. (Letter)</strong>
|
|
J. Med. Genet. 45: 827-831, 2008.
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[PubMed: 18708426]
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[Full Text: https://doi.org/10.1136/jmg.2007.057158]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Cai, G., Nakayama, M., Hiraki, Y., Ozono, K.
|
|
<strong>Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.</strong>
|
|
Am. J. Med. Genet. 78: 58-60, 1998.
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[PubMed: 9637425]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Czarny-Ratajczak, M., Lohiniva, J., Rogala, P., Kozlowski, K., Perala, M., Carter, L., Spector, T. D., Kolodziej, L., Seppanen, U., Glazar, R., Krolewski, J., Latos-Bielenska, A., Ala-Kokko, L.
|
|
<strong>A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity.</strong>
|
|
Am. J. Hum. Genet. 69: 969-980, 2001.
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|
|
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|
|
[PubMed: 11565064]
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[Full Text: https://doi.org/10.1086/324023]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
de la Chapelle, A., Maroteaux, P., Havu, N., Granroth, G.
|
|
<strong>Une rare dysplasie osseuse letale de transmission recessive autosomique.</strong>
|
|
Arch. Franc. Pediat. 29: 759-770, 1972.
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|
|
|
|
|
[PubMed: 4644462]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Forlino, A., Piazza, R., Tiveron, C., Della Torre, S., Tatangelo, L., Bonafe, L., Gualeni, B., Romano, A., Pecora, F., Superti-Furga, A., Cetta, G., Rossi, A.
|
|
<strong>A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.</strong>
|
|
Hum. Molec. Genet. 14: 859-871, 2005.
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[PubMed: 15703192]
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[Full Text: https://doi.org/10.1093/hmg/ddi079]
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, B. D.
|
|
<strong>Diastrophic dysplasia: extreme variability within a sibship.</strong>
|
|
Am. J. Med. Genet. 63: 28-33, 1996.
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|
|
|
|
|
[PubMed: 8723083]
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|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<28::AID-AJMG8>3.0.CO;2-O]
|
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|
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M., Hamilton, B. A., Kusumi, K., Trivedi, B., Weaver, A., Coloma, A., Lovett, M., Buckler, A., Kaitila, I., Lander, E. S.
|
|
<strong>The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.</strong>
|
|
Cell 78: 1073-1087, 1994.
|
|
|
|
|
|
[PubMed: 7923357]
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|
|
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|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90281-x]
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</p>
|
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Hastbacka, J., Kerrebrock, A., Mokkala, K., Clines, G., Lovett, M., Kaitila, I., de la Chapelle, A., Lander, E. S.
|
|
<strong>Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).</strong>
|
|
Europ. J. Hum. Genet. 7: 664-670, 1999.
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|
|
|
|
|
[PubMed: 10482955]
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|
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200361]
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Hastbacka, J., Superti-Furga, A., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Lander, E. S.
|
|
<strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.</strong>
|
|
Am. J. Hum. Genet. 58: 255-262, 1996.
|
|
|
|
|
|
[PubMed: 8571951]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hastbacka, J., Wilcox, W. R., Superti-Furga, A., Rimoin, D. L., Cohn, D. H., Lander, E. S.
|
|
<strong>Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate transporter gene (DTDST). (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A48, 1995.
|
|
|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Rimoin, D. L., Lachman, R. S., Skovby, F., Hollister, D. W., Spranger, J., Scott, C. I., Hall, J. G.
|
|
<strong>The phenotype variability of diastrophic dysplasia.</strong>
|
|
J. Pediat. 93: 609-613, 1978.
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|
|
|
[PubMed: 702237]
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|
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[Full Text: https://doi.org/10.1016/s0022-3476(78)80896-8]
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|
</p>
|
|
</li>
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Huber, C., Odent, S., Rumeur, S., Padovani, P., Penet, C., Cormier-Daire, V., Munnich, A., Le Merrer, M.
|
|
<strong>Sulphate transporter gene mutations in apparently isolated club foot. (Letter)</strong>
|
|
J. Med. Genet. 38: 191-192, 2001.
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|
|
|
|
[PubMed: 11303514]
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|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.38.3.191]
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|
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|
|
</p>
|
|
</li>
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karniski, L. P.
|
|
<strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.</strong>
|
|
Hum. Molec. Genet. 10: 1485-1490, 2001.
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|
|
|
|
[PubMed: 11448940]
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|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.14.1485]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karniski, L. P.
|
|
<strong>Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.</strong>
|
|
Hum. Molec. Genet. 13: 2165-2171, 2004.
|
|
|
|
|
|
[PubMed: 15294877]
|
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|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh242]
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|
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Macias-Gomez, N. M., Megarbane, A., Leal-Ugarte, E., Rodriguez-Rojas, L. X., Barros-Nunez, P.
|
|
<strong>Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.</strong>
|
|
Am. J. Med. Genet. 129A: 190-192, 2004.
|
|
|
|
|
|
[PubMed: 15316973]
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30149]
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Makitie, O., Savarirayan, R., Bonafe, L., Robertson, S., Susic, M., Superti-Furga, A., Cole, W.G.
|
|
<strong>Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.</strong>
|
|
Am. J. Med. Genet. 122A: 187-192, 2003.
|
|
|
|
|
|
[PubMed: 12966518]
|
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|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20282]
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|
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Megarbane, A., Farkh, I., Haddad-Zebouni, S.
|
|
<strong>How many phenotypes in the DTDST family chondrodysplasias? (Letter)</strong>
|
|
Clin. Genet. 62: 189-190, 2002.
|
|
|
|
|
|
[PubMed: 12220459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620214.x]
|
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Megarbane, A., Haddad, F. A., Haddad-Zebouni, S., Achram, M., Eich, G., Le Merrer, M., Superti-Furga, A.
|
|
<strong>Homozygosity for a novel DTDST mutation in a child with a 'broad bone-platyspondylic' variant of diastrophic dysplasia.</strong>
|
|
Clin. Genet. 56: 71-76, 1999.
|
|
|
|
|
|
[PubMed: 10466420]
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|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.1999.560110.x]
|
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Panzer, K. M., Lachman, R., Modaff, P., Pauli, R. M.
|
|
<strong>A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST.</strong>
|
|
Am. J. Med. Genet. 146A: 2920-2924, 2008.
|
|
|
|
|
|
[PubMed: 18925670]
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|
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32543]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rossi, A., Superti-Furga, A.
|
|
<strong>Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance.</strong>
|
|
Hum. Mutat. 17: 159-171, 2001. Note: Erratum: Hum. Mutat. 18: 82 only, 2001.
|
|
|
|
|
|
[PubMed: 11241838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Rossi, A., van der Harten, H. J., Beemer, F. A., Kleijer, W. J., Gitzelmann, R., Steinmann, B., Superti-Furga, A.
|
|
<strong>Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.</strong>
|
|
Hum. Genet. 98: 657-661, 1996.
|
|
|
|
|
|
[PubMed: 8931695]
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|
|
[Full Text: https://doi.org/10.1007/s004390050279]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Satoh, H., Susaki, M., Shukunami, C., Iyama, K., Negoro, T., Hiraki, Y.
|
|
<strong>Functional analysis of diastrophic dysplasia sulfate transporter: its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.</strong>
|
|
J. Biol. Chem. 273: 12307-12315, 1998.
|
|
|
|
|
|
[PubMed: 9575183]
|
|
|
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|
|
[Full Text: https://doi.org/10.1074/jbc.273.20.12307]
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|
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Hastbacka, J., Cohn, D. H., Wilcox, W., van der Harten, H. J., Rimoin, D. L., Lander, E. S., Steinmann, B., Gitzelmann, R.
|
|
<strong>Defective sulfation of proteoglycans in achondrogenesis type 1B is caused by mutations in the DTDST gene: the disorder is allelic to diastrophic dysplasia. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A48, 1995.
|
|
|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Hastbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, H. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., Gitzelmann, R.
|
|
<strong>Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene.</strong>
|
|
Nature Genet. 12: 100-102, 1996.
|
|
|
|
|
|
[PubMed: 8528239]
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|
|
[Full Text: https://doi.org/10.1038/ng0196-100]
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</p>
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Superti-Furga, A., Neumann, L., Riebel, T., Eich, G., Steinmann, B., Spranger, J., Kunze, J.
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<strong>Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.</strong>
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J. Med. Genet. 36: 621-624, 1999.
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[PubMed: 10465113]
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Superti-Furga, A., Rossi, A., Steinmann, B., Gitzelmann, R.
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<strong>A chondrodysplasia family produced by mutations in the diastrophic dysplasia sulfate transporter gene: genotype/phenotype correlations.</strong>
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Am. J. Med. Genet. 63: 144-147, 1996.
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[PubMed: 8723100]
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[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<144::AID-AJMG25>3.0.CO;2-N]
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Sonja A. Rasmussen - updated : 03/22/2019<br>Nara Sobreira - updated : 3/26/2010<br>Cassandra L. Kniffin - updated : 2/11/2009<br>George E. Tiller - updated : 4/25/2008<br>George E. Tiller - updated : 4/5/2007<br>Marla J. F. O'Neill - updated : 10/25/2006<br>Marla J. F. O'Neill - updated : 10/13/2006<br>Marla J. F. O'Neill - updated : 10/7/2004<br>Felicity Collins - updated : 12/5/2003<br>Victor A. McKusick - updated : 11/20/2002<br>Michael J. Wright - updated : 6/28/2002
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Ada Hamosh : 2/25/2002
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