5033 lines
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Entry
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- *612222 - GALACTOSAMINE-6-SULFATE SULFATASE; GALNS
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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">*612222</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/612222">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<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=ENSG00000141012;t=ENST00000268695" 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=2588" 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=612222" 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=ENSG00000141012;t=ENST00000268695" 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_000512,NM_001323543,NM_001323544,XM_005256301,XM_011522982,XM_017023112,XM_017023113,XM_047433889,XM_047433890,XM_047433891,XM_047433892" 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_000512" 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=612222" 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=08357&isoform_id=08357_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/GALNS" 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/462148,618426,870751,4503899,10432682,33440495,34366423,34526537,37547451,37589093,39645009,119587161,119587162,119587163,189069200,221039980,530424707,767989687,1021311727,1021311951,1034594209,1034594211,1036292072,1240501959,1328385895,1859044113,1859044115,1859044117,2217305387,2217305390,2217305393,2217305395,2462548339,2462548341,2462548343,2462548345,2462548347,2462548349,2462548351,2462548353" 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/P34059" 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=2588" 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=ENSG00000141012;t=ENST00000268695" 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=GALNS" 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=GALNS" 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+2588" 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/GALNS" 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:2588" 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/2588" 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=chr16&hgg_gene=ENST00000268695.10&hgg_start=88813734&hgg_end=88856947&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:4122" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:4122" 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/galns" 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=612222[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=612222[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000141012" 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=GALNS" 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=GALNS" 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=GALNS" 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=GALNS&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/PA28535" 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:4122" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1355303" 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/GALNS#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:1355303" 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/2588/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=2588" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00006309;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070112-1152" 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:2588" 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=GALNS&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> 130197005, 7259005<br />
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<strong>ICD10CM:</strong> E76.210<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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612222
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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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GALACTOSAMINE-6-SULFATE SULFATASE; GALNS
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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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N-ACETYLGALACTOSAMINE-SULFATE SULFATASE
|
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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=GALNS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GALNS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/16/739?start=-3&limit=10&highlight=739">16q24.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:88813734-88856947&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'})">16:88,813,734-88,856,947</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
|
|
Location
|
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</th>
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<th>
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Phenotype
|
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</th>
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
|
|
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<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/16/739?start=-3&limit=10&highlight=739">
|
|
16q24.3
|
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</a>
|
|
</span>
|
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</td>
|
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|
|
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<td>
|
|
<span class="mim-font">
|
|
Mucopolysaccharidosis IVA
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/253000"> 253000 </a>
|
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/612222" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>The GALNS gene encodes N-acetylgalactosamine-sulfate sulfatase (<a href="https://enzyme.expasy.org/EC/3.1.6.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.1.6.4</a>), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate.</p>
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<p><a href="#5" class="mim-tip-reference" title="Gibson, G. J., Saccone, G. T. P., Brooks, D. A., Clements, P. R., Hopwood, J. J. <strong>Human N-acetylgalactosamine-4-sulphate sulphatase: purification, monoclonal antibody production and native and subunit M(r) values.</strong> Biochem. J. 248: 755-764, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3435483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3435483</a>] [<a href="https://doi.org/10.1042/bj2480755" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3435483">Gibson et al. (1987)</a> purified and characterized the GALNS enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3435483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Fukao, T., Yamagishi, A., Hori, T., Iwata, H., Ogawa, T., Nakashima, Y., Hanyu, Y., Hashimoto, T., Titani, K., Oyama, R., Suzuki, M., Yagi, K., Hayashi, Y., Orii, T. <strong>Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase.</strong> Biochem. Biophys. Res. Commun. 181: 677-683, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1755850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1755850</a>] [<a href="https://doi.org/10.1016/0006-291x(91)91244-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1755850">Tomatsu et al. (1991)</a> cloned and sequenced a full-length cDNA of human placental N-acetylgalactosamine-6-sulfate sulfatase. The deduced 522-residue protein is composed of a 26-amino acid N-terminal signal peptide and a mature polypeptide of 496 amino acid residues, including 2 potential asparagine-linked glycosylation sites. Expression of the cDNA in transfected deficient fibroblasts resulted in higher production of the sulfatase activity compared to untransfected cells. The amino acid sequence showed a high degree of homology with those of other sulfatases, including human arylsulfatases A (<a href="/entry/607574">607574</a>), B (<a href="/entry/611542">611542</a>), and C (<a href="/entry/300747">300747</a>), glucosamine-6-sulfatase (<a href="/entry/607664">607664</a>), and iduronate-2-sulfatase (<a href="/entry/300823">300823</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1755850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Nakashima, Y., Tomatsu, S., Hori, T., Fukuda, S., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T. <strong>Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5-prime-flanking region.</strong> Genomics 20: 99-104, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8020961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8020961</a>] [<a href="https://doi.org/10.1006/geno.1994.1132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8020961">Nakashima et al. (1994)</a> determined that the human GALNS gene contains 14 exons and spans approximately 50 kb. By deletion analysis, they found the region -98 to -1 upstream of the ATG codon to be a minimal promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8020961" 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="Morris, C. P., Guo, X.-H., Apostolou, S., Hopwood, J. J., Scott, H. S. <strong>Morquio A syndrome: cloning, sequence, and structure of the human N-acetylgalactosamine 6-sulfatase (GALNS) gene.</strong> Genomics 22: 652-654, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001980</a>] [<a href="https://doi.org/10.1006/geno.1994.1443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001980">Morris et al. (1994)</a> found that the GALNS gene contains 14 exons and spans approximately 40 kb. The potential promoter for GALNS lacks a TATA box but contains GC box consensus sequences, consistent with its role as a housekeeping gene. The GALNS gene contains an Alu repeat in intron 5 and a VNTR-like sequence in intron 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001980" 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="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> demonstrated that the GALNS gene is located on chromosome 16q24 by fluorescence in situ hybridization. <a href="#1" class="mim-tip-reference" title="Baker, E., Guo, X.-H., Orsborn, A. M., Sutherland, G. R., Callen, D. F., Hopwood, J. J., Morris, C. P. <strong>The Morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3.</strong> Am. J. Hum. Genet. 52: 96-98, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434612</a>]" pmid="8434612">Baker et al. (1993)</a>, also using fluorescence in situ hybridization, mapped the gene to 16q24.3. The authors also confirmed the localization to this band by PCR analysis of the somatic cell hybrid panel used for fine mapping of chromosome 16. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In patients with mucopolysaccharidosis type IVA (<a href="/entry/253000">253000</a>), also known as Morquio syndrome A, <a href="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> identified 4 different mutations in the GALNS gene (<a href="#0001">612222.0001</a>-<a href="#0004">612222.0004</a>).</p><p>In 5 unrelated Japanese patients with MPS IVA, <a href="#6" class="mim-tip-reference" title="Hori, T., Tomatsu, S., Nakashima, Y., Uchiyama, A., Fukuda, S., Sukegawa, K., Shimozawa, N., Suzuki, Y., Kondo, N., Horiuchi, T., Ogura, S., Orii, T. <strong>Mucopolysaccharidosis type IVA: common double deletion in the N-acetylgalactosamine-6-sulfatase gene (GALNS).</strong> Genomics 26: 535-542, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7607677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7607677</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80172-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7607677">Hori et al. (1995)</a> found, in heteroallelic state, 2 separate deletions of nearly 8.0 and 6.0 kb in the GALNS gene. There were Alu repetitive elements near the breakpoints of the 8.0-kb deletion; this deletion had clearly resulted from an Alu-Alu recombination. The 6.0-kb deletion involved illegitimate recombinational events between incomplete short direct repeats of 8 bp at the deletion breakpoints. This was the first documentation of a frequently occurring double deletion in a gene that is not a member of a gene cluster. One of the patients was homozygous for the double deletion, and the others were heterozygous. In the 4 who were heterozygous, <a href="#18" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Yamagishi, A., Cooper, A., Wraith, J. E., Hori, T., Kato, Z., Yamada, N., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T. <strong>Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.</strong> Am. J. Hum. Genet. 58: 950-962, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651279</a>]" pmid="8651279">Tomatsu et al. (1996)</a> identified novel mutations in the GALNS gene on the other allele: 1 nonsense and 3 missense. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8651279+7607677" 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="Wang, Z., Zhang, W., Wang, Y., Meng, Y., Su, L., Shi, H., Huang, S. <strong>Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.</strong> J. Hum. Genet. 55: 534-540, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20574428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20574428</a>] [<a href="https://doi.org/10.1038/jhg.2010.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20574428">Wang et al. (2010)</a> identified 27 GALNS mutations, including 16 novel mutations, among 24 Chinese patients with MPS IVA. Approximately 63% of the mutations found among the Chinese patients were not observed in other countries, suggesting that a different mutational spectrum may exist in the Chinese population. The most common mutation G340D (<a href="#0018">612222.0018</a>) was present in 8 (16.7%) of 48 mutant alleles and was found only in 5 patients from central eastern China. Haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20574428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Caciotti, A., Tonin, R., Rigoldi, M., Ferri, L., Catarzi, S., Cavicchi, C., Procopio, E., Donati, M. A., Ficcadenti, A., Fiumara, A., Barone, R., Garavelli, L., and 16 others. <strong>Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio--A syndrome-associated mutations.</strong> Hum. Mutat. 36: 357-368, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25545067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25545067</a>] [<a href="https://doi.org/10.1002/humu.22751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25545067">Caciotti et al. (2015)</a> studied 37 Italian MPS IVA patients and found that standard sequencing procedures failed to characterize the second disease-causing mutation in 16 percent of patients. Searching for large rearrangements and mRNA defects in this 16% identified splicing defects or large deletions on the other allele in 67% of these. <a href="#3" class="mim-tip-reference" title="Caciotti, A., Tonin, R., Rigoldi, M., Ferri, L., Catarzi, S., Cavicchi, C., Procopio, E., Donati, M. A., Ficcadenti, A., Fiumara, A., Barone, R., Garavelli, L., and 16 others. <strong>Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio--A syndrome-associated mutations.</strong> Hum. Mutat. 36: 357-368, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25545067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25545067</a>] [<a href="https://doi.org/10.1002/humu.22751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25545067">Caciotti et al. (2015)</a> reported 14 novel mutations in GALNS among the 37 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25545067" 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="#12" class="mim-tip-reference" title="Sukegawa, K., Nakamura, H., Kato, Z., Tomatsu, S., Montano, A. M., Fukao, T., Toietta, G., Tortora, P., Orii, T., Kondo, N. <strong>Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.</strong> Hum. Molec. Genet. 9: 1283-1290, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814710</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814710">Sukegawa et al. (2000)</a> studied 15 missense mutations and 2 newly engineered active site mutations (C79S, C79T) in the GALNS gene by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms, while the C79S and C79T mutants were of a soluble mature size. Mutations identified in patients with the severe phenotype had no activity, whereas mutations identified in patients with the mild phenotype had a considerable residual activity (1.3-13.3% of wildtype GALNS activity). <a href="#12" class="mim-tip-reference" title="Sukegawa, K., Nakamura, H., Kato, Z., Tomatsu, S., Montano, A. M., Fukao, T., Toietta, G., Tortora, P., Orii, T., Kondo, N. <strong>Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.</strong> Hum. Molec. Genet. 9: 1283-1290, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814710</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814710">Sukegawa et al. (2000)</a> also constructed a tertiary structural model of human GALNS from the x-ray crystal structure of homologous sulfatases and investigated 32 missense mutations. The authors proposed 3 different biochemical models for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10814710" 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="#19" class="mim-tip-reference" title="Tomatsu, S., Orii, K. O., Vogler, C., Nakayama, J., Levy, B., Grubb, J. H., Gutierrez, M. A., Shim, S., Yamaguchi, S., Nishioka, T., Montano, A. M., Noguchi, A., Orii, T., Kondo, N., Sly, W. S. <strong>Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease.</strong> Hum. Molec. Genet. 12: 3349-3358, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14583446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14583446</a>] [<a href="https://doi.org/10.1093/hmg/ddg366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14583446">Tomatsu et al. (2003)</a> generated transgenic mice homozygous for a disruption in exon 2 of the Galns gene. These mice had no detectable GALNS enzyme activity, showed increased urinary glycosaminoglycan levels, and accumulated glycosaminoglycans in multiple tissues including liver, kidney, spleen, heart, brain, and bone marrow. At 2 months old, lysosomal storage was present primarily within reticuloendothelial cells. By 12 months old, vacuolar change was observed in glomeruli and heart valves. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage, and keratan sulfate and chondroitin-6-sulfate were more abundant in corneal epithelial cells of Galns -/- mice. Surprisingly, radiographs revealed no change in the skeletal bones of mice up to 12 months old. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=612222[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118204435 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204435;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=rs118204435" 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=rs118204435" 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=RCV000000733" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000733" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000733</a>
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<p>In 2 brothers with a mild form of Morquio syndrome A (<a href="/entry/253000">253000</a>), <a href="#4" class="mim-tip-reference" title="Fukuda, S., Tomatsu, S., Masue, M., Sukegawa, K., Iwata, H., Ogawa, T., Nakashima, Y., Hori, T., Yamagishi, A., Hanyu, Y., Morooka, K., Kiman, T., Hashimoto, T., Orii, T. <strong>Mucopolysaccharidosis type IVA: N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.</strong> J. Clin. Invest. 90: 1049-1053, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1522213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1522213</a>] [<a href="https://doi.org/10.1172/JCI115919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1522213">Fukuda et al. (1992)</a> and <a href="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> identified a homozygous 667C-G transversion in the GALNS gene, resulting in an asn204-to-lys (N204K) substitution. Both unaffected parents were heterozygous for the mutation. Transient expression of the mutant allele in GALNS-deficient fibroblasts showed markedly decreased enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1522213" 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 MUCOPOLYSACCHARIDOSIS, TYPE IVA</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">rs118204436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204436;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=rs118204436" 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=rs118204436" 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=RCV000000734" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000734" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000734</a>
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<p>In a patient with a severe form of Morquio syndrome A (<a href="/entry/253000">253000</a>), <a href="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> identified a homozygous 468T-C transition in the GALNS gene, resulting in an ala138-to-val (A138V) substitution.</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> rs118204437 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204437;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/rs118204437?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=rs118204437" 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=rs118204437" 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=RCV000000735 OR RCV000079019 OR RCV000781397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000735, RCV000079019, RCV000781397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000735...</a>
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<p>In a patient with severe Morquio syndrome A (<a href="/entry/253000">253000</a>), <a href="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> identified a 386C-T transition in the GALNS gene, resulting in an arg386-to-cys (R386C) substitution. A PCR method was used for complete cDNA sequencing.</p><p>In a study of 20 MPS IVA patients from Latin America, including 16 with a severe phenotype and 4 with an attenuated phenotype, <a href="#13" class="mim-tip-reference" title="Tomatsu, S., Dieter, T., Schwartz, I. V., Sarmient, P., Giugliani, R., Barrera, L. A., Guelbert, N., Kremer, R., Repetto, G. M., Gutierrez, M. A., Nishioka, T., Serrato, O. P., Montano, A. M., Yamaguchi, S., Noguchi, A. <strong>Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate.</strong> J. Hum. Genet. 49: 490-494, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15309681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15309681</a>] [<a href="https://doi.org/10.1007/s10038-004-0178-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15309681">Tomatsu et al. (2004)</a> identified 12 different mutations in the GALNS gene, 9 of which were previously unreported. The R386C mutation accounted for 32.5% of the unrelated mutant alleles. It was identified in all the Latin American populations studied and was associated with a severe form of the disorder. MPS IVA patients had increased urine and plasma keratan sulfate concentrations compared to normal controls. Keratan sulfate concentrations were higher in patients with a severe phenotype than in those with the attenuated form of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15309681" 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">rs2142992359 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2142992359;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=rs2142992359" 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=rs2142992359" 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=RCV001578607" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001578607" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001578607</a>
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<p>In a Japanese patient, born of consanguineous parents, with a severe form of Morquio syndrome A (<a href="/entry/253000">253000</a>), <a href="#4" class="mim-tip-reference" title="Fukuda, S., Tomatsu, S., Masue, M., Sukegawa, K., Iwata, H., Ogawa, T., Nakashima, Y., Hori, T., Yamagishi, A., Hanyu, Y., Morooka, K., Kiman, T., Hashimoto, T., Orii, T. <strong>Mucopolysaccharidosis type IVA: N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.</strong> J. Clin. Invest. 90: 1049-1053, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1522213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1522213</a>] [<a href="https://doi.org/10.1172/JCI115919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1522213">Fukuda et al. (1992)</a> and <a href="#17" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T. <strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A178, 1992."None>Tomatsu et al. (1992)</a> identified a homozygous 2-bp deletion in the GALNS gene (1343delCA). <a href="#4" class="mim-tip-reference" title="Fukuda, S., Tomatsu, S., Masue, M., Sukegawa, K., Iwata, H., Ogawa, T., Nakashima, Y., Hori, T., Yamagishi, A., Hanyu, Y., Morooka, K., Kiman, T., Hashimoto, T., Orii, T. <strong>Mucopolysaccharidosis type IVA: N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.</strong> J. Clin. Invest. 90: 1049-1053, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1522213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1522213</a>] [<a href="https://doi.org/10.1172/JCI115919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1522213">Fukuda et al. (1992)</a> referred to the mutation as 1342delCA. This mutation was revealed by TaqI restriction analysis of a cDNA fragment amplified by the polymerase chain reaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1522213" 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="0005" class="mim-anchor"></a>
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<strong>.0005 MUCOPOLYSACCHARIDOSIS, TYPE IVA</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> rs118204438 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204438;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/rs118204438?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=rs118204438" 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=rs118204438" 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=RCV000000738 OR RCV000295527 OR RCV000723431" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000738, RCV000295527, RCV000723431" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000738...</a>
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<p>In Caucasian patients with Morquio syndrome A (<a href="/entry/253000">253000</a>), <a href="#14" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Rezvi, G. M. M., Yamagishi, A., Yamada, N., Kato, Z., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T. <strong>Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-acetylgalactosamine-6-sulfate sulfatase gene.</strong> Am. J. Hum. Genet. 57: 556-563, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668283</a>]" pmid="7668283">Tomatsu et al. (1995)</a> identified a 393A-T transversion in the GALNS gene, resulting in an ile113-to-phe (I113F) substitution. Allele-specific oligonucleotide (ASO) or SSCP analysis indicated that this mutation accounted for 9 (22.5%) of 40 unrelated mutant chromosomes from 23 Caucasian patients, including 6 consanguineous cases. It was not found among 20 Japanese patients. In addition to this common mutation, 10 different point mutations and 2 small deletions were detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668283" 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>Among 23 Australian or Irish patients with Morquio syndrome A and various clinical phenotypes, <a href="#22" class="mim-tip-reference" title="Yamada, N., Fukuda, S., Tomatsu, S., Muller, V., Hopwood, J. J., Nelson, J., Kato, Z., Yamagishi, A., Sukegawa, K., Kondo, N., Orii, T. <strong>Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.</strong> Hum. Mutat. 11: 202-208, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9521421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9521421</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9521421">Yamada et al. (1998)</a> found that the I113F mutation was associated with a severe phenotype. The relative frequency of the I113F mutation in Australia corresponded to that observed in Northern Ireland, suggesting that both mutations were probably introduced to Australia by Irish migrants during the 19th century. Haplotype analysis provided additional data that the I113F mutation originated from a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9521421" 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 MUCOPOLYSACCHARIDOSIS, TYPE IVA</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> rs118204439 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204439;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/rs118204439?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=rs118204439" 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=rs118204439" 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=RCV000000739" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000739" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000739</a>
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<p>In a patient with severe Morquio disease (<a href="/entry/253000">253000</a>), <a href="#15" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Yamada, N., Isogai, K., Kato, Z., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T. <strong>Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease).</strong> Hum. Mutat. 6: 195-196, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581409</a>] [<a href="https://doi.org/10.1002/humu.1380060218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581409">Tomatsu et al. (1995)</a> identified compound heterozygosity for 2 mutations in exon 13 of the GALNS gene: a C-to-T transition resulting in a gln473-to-ter (Q473X) substitution, and an A-to-G transition resulting in an asn487-to-ser substitution (N487S; <a href="#0007">612222.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581409" 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 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
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GALNS, ASN487SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118204440 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204440;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=rs118204440" 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=rs118204440" 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=RCV000000736" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000736" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000736</a>
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<p>See <a href="#0006">612222.0006</a> and <a href="#15" class="mim-tip-reference" title="Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Yamada, N., Isogai, K., Kato, Z., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T. <strong>Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease).</strong> Hum. Mutat. 6: 195-196, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581409</a>] [<a href="https://doi.org/10.1002/humu.1380060218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581409">Tomatsu et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581409" 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 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
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GALNS, ARG94GLY
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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> rs118204441 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204441;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/rs118204441?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=rs118204441" 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=rs118204441" 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=RCV000000740" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000740" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000740</a>
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<p>In 2 Polish sibs with Morquio syndrome (<a href="/entry/253000">253000</a>), <a href="#2" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Tylki-Szymanska, A., Steglich, C., Beck, M., Tomatsu, S., Fukuda, S., Poorthuis, B. J. H. M., Czartoryska, B., Orii, T., Gal, A. <strong>Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.</strong> Hum. Mutat. 10: 223-232, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298823</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298823">Bunge et al. (1997)</a> identified compound heterozygosity for 2 mutations in the GALNS gene: an arg94-to-gly (R94G) substitution inherited from the father and an arg259-to-gln (R259Q; <a href="#0009">612222.0009</a>) substitution inherited from the mother. The sibs were diagnosed at 5 and 6 years of age, respectively. At ages 13 and 14, they were still considered to be mildly affected, with mild thoracolumbar kyphosis, slight prominence of the sternum, hypermobility of ligaments, hip hypoplasia in the boy only, no corneal clouding, and normal height. Their mother, who was homozygous for the R259Q mutation, was found to have greatly reduced enzymatic activity, but only limited manifestations of MPS IVA: short trunk with slight prominence of sternum, and hoarse voice. She had no corneal clouding and was 1.60 m tall. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 MUCOPOLYSACCHARIDOSIS, TYPE IVA</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> rs118204442 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204442;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/rs118204442?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=rs118204442" 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=rs118204442" 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=RCV000000741 OR RCV004777560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000741, RCV004777560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000741...</a>
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<p>See <a href="#0008">612222.0008</a> and <a href="#2" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Tylki-Szymanska, A., Steglich, C., Beck, M., Tomatsu, S., Fukuda, S., Poorthuis, B. J. H. M., Czartoryska, B., Orii, T., Gal, A. <strong>Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.</strong> Hum. Mutat. 10: 223-232, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298823</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298823">Bunge et al. (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Tylki-Szymanska, A., Czartoryska, B., Bunge, S., van Diggelen, O. P., Kleijer, W. J., Poorthuis, B. J. H. M., Huijmans, J. G. M., Gorska, D. <strong>Clinical, biochemical and molecular findings in a two-generation Morquio A family.</strong> Clin. Genet. 53: 369-374, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9660054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9660054</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02747.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9660054">Tylki-Szymanska et al. (1998)</a> described a 2-generation Morquio A (<a href="/entry/253000">253000</a>) family with 2 distinct clinical phenotypes. The 2 probands from the second generation showed intermediate signs of the disease, whereas their affected mother, aunt, and 2 uncles had only very mild symptoms. Galactose-6-sulfatase activity in leukocytes and fibroblasts of the affected family members was clearly deficient. Molecular genetic analysis of the GALNS gene showed that 2 different point mutations segregated in the family and correlated well with the clinical phenotype. The probands with intermediate severity of symptoms were compound heterozygous for the R94G mutation (<a href="#0008">612222.0008</a>), which was inherited from the unaffected father, and for R259Q. The mother and her affected sibs with the unusually mild phenotype were homozygous for the R259Q mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9660054" 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> rs118204443 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204443;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/rs118204443?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=rs118204443" 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=rs118204443" 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=RCV000000743 OR RCV000781400 OR RCV000790840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000743, RCV000781400, RCV000790840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000743...</a>
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<p><a href="#7" class="mim-tip-reference" title="Kato, Z., Fukuda, S., Tomatsu, S., Vega, H., Yasunaga, T., Yamagishi, A., Yamada, N., Valencia, A., Barrera, L. A., Sukegawa, K., Orii, T., Kondo, N. <strong>A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.</strong> Hum. Genet. 101: 97-101, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385378</a>] [<a href="https://doi.org/10.1007/s004390050594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385378">Kato et al. (1997)</a> identified 3 novel missense mutations in 16 of 19 Colombian Morquio syndrome A unrelated alleles (84.2%). A gly301-to-cys (G301C) mutation and a S162F (<a href="#0011">612222.0011</a>) mutation accounted for 68.4% and 10.5% of mutations, respectively, whereas the third mutation, F69V, (<a href="#0012">612222.0012</a>), was limited to a single allele. The skewed prevalence of G301C in Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggested that G301C originated from a common ancestor. Investigation of a genetic background by means of mtDNA lineages indicated that all of the Colombian patients were probably of Native American descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385378" 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> rs118204444 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204444;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/rs118204444?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=rs118204444" 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=rs118204444" 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=RCV000000744 OR RCV000723452" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000744, RCV000723452" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000744...</a>
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<p>See <a href="#0010">612222.0010</a> and <a href="#7" class="mim-tip-reference" title="Kato, Z., Fukuda, S., Tomatsu, S., Vega, H., Yasunaga, T., Yamagishi, A., Yamada, N., Valencia, A., Barrera, L. A., Sukegawa, K., Orii, T., Kondo, N. <strong>A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.</strong> Hum. Genet. 101: 97-101, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385378</a>] [<a href="https://doi.org/10.1007/s004390050594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385378">Kato et al. (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385378" 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">rs118204445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204445;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=rs118204445" 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=rs118204445" 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=RCV000000745" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000745" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000745</a>
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<p>See <a href="#0010">612222.0010</a> and <a href="#7" class="mim-tip-reference" title="Kato, Z., Fukuda, S., Tomatsu, S., Vega, H., Yasunaga, T., Yamagishi, A., Yamada, N., Valencia, A., Barrera, L. A., Sukegawa, K., Orii, T., Kondo, N. <strong>A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.</strong> Hum. Genet. 101: 97-101, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385378</a>] [<a href="https://doi.org/10.1007/s004390050594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385378">Kato et al. (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385378" 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> rs118204446 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204446;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/rs118204446?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=rs118204446" 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=rs118204446" 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=RCV000000748 OR RCV001193737" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000748, RCV001193737" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000748...</a>
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<p>Studies of patients from the British-Irish population have shown that the I113F (<a href="#0005">612222.0005</a>) mutation in the GALNS gene is the most common single mutation among Morquio syndrome A patients and produces a severe clinical phenotype. <a href="#22" class="mim-tip-reference" title="Yamada, N., Fukuda, S., Tomatsu, S., Muller, V., Hopwood, J. J., Nelson, J., Kato, Z., Yamagishi, A., Sukegawa, K., Kondo, N., Orii, T. <strong>Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.</strong> Hum. Mutat. 11: 202-208, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9521421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9521421</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9521421">Yamada et al. (1998)</a> studied mutations in the GALNS gene from 23 additional patients (15 from Australia, 8 from Northern Ireland) with various clinical phenotypes (severe, 16 cases; intermediate, 4 cases; mild, 3 cases). They found 2 common mutations that together accounted for 32% of the 44 unrelated alleles in these patients. One was a thr312-to-ser (T312S) substitution, found exclusively in milder patients, and the other was I113F, which produced a severe phenotype. Relatively high residual GALNS activity seen when the T312S mutant cDNA was overexpressed in mutant cells provided an explanation for the mild phenotype in patients with this mutation. The disruption and relative frequency of the I113F and T312S mutations in Australia corresponded to those observed in Northern Ireland and were unique to these 2 populations, suggesting that both mutations were probably introduced to Australia by Irish migrants during the 19th century. Haplotype analysis provided additional data that the I113F mutation originated from a common ancestor. The other 9 novel mutations identified in these 23 patients were each limited to a single family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9521421" 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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GALNS, ASP60ASN
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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> rs118204447 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204447;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/rs118204447?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=rs118204447" 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=rs118204447" 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=RCV000000749" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000749" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000749</a>
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<p><a href="#9" class="mim-tip-reference" title="Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N. <strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong> Hum. Genet. 113: 162-169, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12721840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12721840</a>] [<a href="https://doi.org/10.1007/s00439-003-0959-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12721840">Montano et al. (2003)</a> described the clinical phenotype of 5 patients from 3 unrelated Finnish families with Morquio A disease and characterized the disease-causing mutations in GALNS. In all 3 families the affected individuals were compound heterozygous for an asp60-to-asn (D60N) mutation and a second mutation: A291T (<a href="#0015">612222.0015</a>) and W230X (<a href="#0016">612222.0016</a>) in 2 of the families, and 1374delT (<a href="#0017">612222.0017</a>) causing premature termination in a third. W230X and A291T had no residual GALNS activity when overexpressed in cultured cells, whereas D60N had 12.2% residual activity compared with wildtype. The tertiary structural model of the GALNS protein showed that asp60 is located on the surface of the molecule, away from the active site. On the other hand, ala291 and trp230 are localized near the active site. The molecular characteristics of the D60N mutation explained the attenuated clinical phenotype of the patients. The oldest patient was 9 years of age, and the youngest 3 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12721840" 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">rs118204448 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204448;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=rs118204448" 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=rs118204448" 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=RCV000000742 OR RCV003234884" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000742, RCV003234884" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000742...</a>
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<p>See <a href="#0014">612222.0014</a> and <a href="#9" class="mim-tip-reference" title="Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N. <strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong> Hum. Genet. 113: 162-169, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12721840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12721840</a>] [<a href="https://doi.org/10.1007/s00439-003-0959-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12721840">Montano et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12721840" 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">rs118204449 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204449;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=rs118204449" 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=rs118204449" 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=RCV000000746 OR RCV001193132" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000746, RCV001193132" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000746...</a>
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<p>See <a href="#0014">612222.0014</a> and <a href="#9" class="mim-tip-reference" title="Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N. <strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong> Hum. Genet. 113: 162-169, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12721840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12721840</a>] [<a href="https://doi.org/10.1007/s00439-003-0959-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12721840">Montano et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12721840" 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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GALNS, 1-BP DEL, 1374T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1567517083 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567517083;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=rs1567517083" 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=rs1567517083" 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=RCV001578608" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001578608" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001578608</a>
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<p>See <a href="#0014">612222.0014</a> and <a href="#9" class="mim-tip-reference" title="Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N. <strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong> Hum. Genet. 113: 162-169, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12721840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12721840</a>] [<a href="https://doi.org/10.1007/s00439-003-0959-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12721840">Montano et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12721840" 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">rs267606838 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606838;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=rs267606838" 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=rs267606838" 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=RCV000000750 OR RCV003155036" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000750, RCV003155036" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000750...</a>
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<p>In 5 of 24 Chinese patients with MPS IVA (<a href="/entry/253000">253000</a>), <a href="#21" class="mim-tip-reference" title="Wang, Z., Zhang, W., Wang, Y., Meng, Y., Su, L., Shi, H., Huang, S. <strong>Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.</strong> J. Hum. Genet. 55: 534-540, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20574428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20574428</a>] [<a href="https://doi.org/10.1038/jhg.2010.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20574428">Wang et al. (2010)</a> identified a 1019G-A transition in exon 10 of the GALNS gene, resulting in a gly340-to-asp (G340D) substitution. Three patients were homozygous, and 2 patients were compound heterozygous for G340D and another mutation. G340D was the most common mutant allele, accounting for 16.7% of the total number of mutant alleles. Haplotype analysis indicated a founder effect, and all 5 patients were residents of or emigrants from central eastern China. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20574428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Masuno1993" class="mim-tip-reference" title="Masuno, M., Tomatsu, S., Nakashima, Y., Hori, T., Fukuda, S., Masue, M., Sukegawa, K., Orii, T. <strong>Mucopolysaccharidosis IV A: assignment of the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene to chromosome 16q24.</strong> Genomics 16: 777-778, 1993.">Masuno et al. (1993)</a>
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Baker, E., Guo, X.-H., Orsborn, A. M., Sutherland, G. R., Callen, D. F., Hopwood, J. J., Morris, C. P.
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<strong>The Morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3.</strong>
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Am. J. Hum. Genet. 52: 96-98, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
<a id="Bunge1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bunge, S., Kleijer, W. J., Tylki-Szymanska, A., Steglich, C., Beck, M., Tomatsu, S., Fukuda, S., Poorthuis, B. J. H. M., Czartoryska, B., Orii, T., Gal, A.
|
|
<strong>Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.</strong>
|
|
Hum. Mutat. 10: 223-232, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Caciotti2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caciotti, A., Tonin, R., Rigoldi, M., Ferri, L., Catarzi, S., Cavicchi, C., Procopio, E., Donati, M. A., Ficcadenti, A., Fiumara, A., Barone, R., Garavelli, L., and 16 others.
|
|
<strong>Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio--A syndrome-associated mutations.</strong>
|
|
Hum. Mutat. 36: 357-368, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25545067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25545067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25545067" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.22751" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Fukuda1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fukuda, S., Tomatsu, S., Masue, M., Sukegawa, K., Iwata, H., Ogawa, T., Nakashima, Y., Hori, T., Yamagishi, A., Hanyu, Y., Morooka, K., Kiman, T., Hashimoto, T., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.</strong>
|
|
J. Clin. Invest. 90: 1049-1053, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1522213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1522213</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1522213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115919" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gibson1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gibson, G. J., Saccone, G. T. P., Brooks, D. A., Clements, P. R., Hopwood, J. J.
|
|
<strong>Human N-acetylgalactosamine-4-sulphate sulphatase: purification, monoclonal antibody production and native and subunit M(r) values.</strong>
|
|
Biochem. J. 248: 755-764, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3435483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3435483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3435483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/bj2480755" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Hori1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hori, T., Tomatsu, S., Nakashima, Y., Uchiyama, A., Fukuda, S., Sukegawa, K., Shimozawa, N., Suzuki, Y., Kondo, N., Horiuchi, T., Ogura, S., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: common double deletion in the N-acetylgalactosamine-6-sulfatase gene (GALNS).</strong>
|
|
Genomics 26: 535-542, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7607677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7607677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7607677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(95)80172-i" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Kato1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kato, Z., Fukuda, S., Tomatsu, S., Vega, H., Yasunaga, T., Yamagishi, A., Yamada, N., Valencia, A., Barrera, L. A., Sukegawa, K., Orii, T., Kondo, N.
|
|
<strong>A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.</strong>
|
|
Hum. Genet. 101: 97-101, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s004390050594" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Masuno1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Masuno, M., Tomatsu, S., Nakashima, Y., Hori, T., Fukuda, S., Masue, M., Sukegawa, K., Orii, T.
|
|
<strong>Mucopolysaccharidosis IV A: assignment of the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene to chromosome 16q24.</strong>
|
|
Genomics 16: 777-778, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8325655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8325655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8325655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1266" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Montano2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N.
|
|
<strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong>
|
|
Hum. Genet. 113: 162-169, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12721840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12721840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12721840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-003-0959-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Morris1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morris, C. P., Guo, X.-H., Apostolou, S., Hopwood, J. J., Scott, H. S.
|
|
<strong>Morquio A syndrome: cloning, sequence, and structure of the human N-acetylgalactosamine 6-sulfatase (GALNS) gene.</strong>
|
|
Genomics 22: 652-654, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1443" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Nakashima1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakashima, Y., Tomatsu, S., Hori, T., Fukuda, S., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5-prime-flanking region.</strong>
|
|
Genomics 20: 99-104, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8020961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8020961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8020961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1132" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Sukegawa2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sukegawa, K., Nakamura, H., Kato, Z., Tomatsu, S., Montano, A. M., Fukao, T., Toietta, G., Tortora, P., Orii, T., Kondo, N.
|
|
<strong>Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.</strong>
|
|
Hum. Molec. Genet. 9: 1283-1290, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814710</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10814710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.9.1283" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Tomatsu2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Dieter, T., Schwartz, I. V., Sarmient, P., Giugliani, R., Barrera, L. A., Guelbert, N., Kremer, R., Repetto, G. M., Gutierrez, M. A., Nishioka, T., Serrato, O. P., Montano, A. M., Yamaguchi, S., Noguchi, A.
|
|
<strong>Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate.</strong>
|
|
J. Hum. Genet. 49: 490-494, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15309681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15309681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15309681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10038-004-0178-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Tomatsu1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Rezvi, G. M. M., Yamagishi, A., Yamada, N., Kato, Z., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-acetylgalactosamine-6-sulfate sulfatase gene.</strong>
|
|
Am. J. Hum. Genet. 57: 556-563, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Tomatsu1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Yamada, N., Isogai, K., Kato, Z., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease).</strong>
|
|
Hum. Mutat. 6: 195-196, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380060218" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Tomatsu1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Fukao, T., Yamagishi, A., Hori, T., Iwata, H., Ogawa, T., Nakashima, Y., Hanyu, Y., Hashimoto, T., Titani, K., Oyama, R., Suzuki, M., Yagi, K., Hayashi, Y., Orii, T.
|
|
<strong>Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 677-683, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1755850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1755850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1755850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)91244-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Tomatsu1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A178, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Tomatsu1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Yamagishi, A., Cooper, A., Wraith, J. E., Hori, T., Kato, Z., Yamada, N., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.</strong>
|
|
Am. J. Hum. Genet. 58: 950-962, 1996.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<a id="19" class="mim-anchor"></a>
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<a id="Tomatsu2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tomatsu, S., Orii, K. O., Vogler, C., Nakayama, J., Levy, B., Grubb, J. H., Gutierrez, M. A., Shim, S., Yamaguchi, S., Nishioka, T., Montano, A. M., Noguchi, A., Orii, T., Kondo, N., Sly, W. S.
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<strong>Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease.</strong>
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Hum. Molec. Genet. 12: 3349-3358, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14583446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14583446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583446" 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/ddg366" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Tylki-Szymanska1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tylki-Szymanska, A., Czartoryska, B., Bunge, S., van Diggelen, O. P., Kleijer, W. J., Poorthuis, B. J. H. M., Huijmans, J. G. M., Gorska, D.
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<strong>Clinical, biochemical and molecular findings in a two-generation Morquio A family.</strong>
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Clin. Genet. 53: 369-374, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9660054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9660054</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9660054" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02747.x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Wang2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, Z., Zhang, W., Wang, Y., Meng, Y., Su, L., Shi, H., Huang, S.
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<strong>Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.</strong>
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J. Hum. Genet. 55: 534-540, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20574428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20574428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20574428" 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/jhg.2010.65" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Yamada1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamada, N., Fukuda, S., Tomatsu, S., Muller, V., Hopwood, J. J., Nelson, J., Kato, Z., Yamagishi, A., Sukegawa, K., Kondo, N., Orii, T.
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<strong>Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.</strong>
|
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Hum. Mutat. 11: 202-208, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9521421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9521421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9521421" 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)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/28/2015
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 11/1/2010
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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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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Cassandra L. Kniffin : 8/4/2008
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/30/2018
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 09/28/2015<br>mcolton : 2/12/2014<br>wwang : 1/10/2011<br>wwang : 12/9/2010<br>wwang : 12/8/2010<br>ckniffin : 11/1/2010<br>carol : 9/1/2010<br>carol : 10/31/2008<br>carol : 8/28/2008<br>carol : 8/27/2008<br>ckniffin : 8/22/2008
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 612222
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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GALACTOSAMINE-6-SULFATE SULFATASE; GALNS
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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N-ACETYLGALACTOSAMINE-SULFATE SULFATASE
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</h4>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GALNS</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 130197005, 7259005;
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<strong>ICD10CM:</strong> E76.210;
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</span>
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</p>
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<br />
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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: 16q24.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 16:88,813,734-88,856,947 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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16q24.3
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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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Mucopolysaccharidosis IVA
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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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253000
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The GALNS gene encodes N-acetylgalactosamine-sulfate sulfatase (EC 3.1.6.4), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gibson et al. (1987) purified and characterized the GALNS enzyme. </p><p>Tomatsu et al. (1991) cloned and sequenced a full-length cDNA of human placental N-acetylgalactosamine-6-sulfate sulfatase. The deduced 522-residue protein is composed of a 26-amino acid N-terminal signal peptide and a mature polypeptide of 496 amino acid residues, including 2 potential asparagine-linked glycosylation sites. Expression of the cDNA in transfected deficient fibroblasts resulted in higher production of the sulfatase activity compared to untransfected cells. The amino acid sequence showed a high degree of homology with those of other sulfatases, including human arylsulfatases A (607574), B (611542), and C (300747), glucosamine-6-sulfatase (607664), and iduronate-2-sulfatase (300823). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nakashima et al. (1994) determined that the human GALNS gene contains 14 exons and spans approximately 50 kb. By deletion analysis, they found the region -98 to -1 upstream of the ATG codon to be a minimal promoter. </p><p>Morris et al. (1994) found that the GALNS gene contains 14 exons and spans approximately 40 kb. The potential promoter for GALNS lacks a TATA box but contains GC box consensus sequences, consistent with its role as a housekeeping gene. The GALNS gene contains an Alu repeat in intron 5 and a VNTR-like sequence in intron 6. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Tomatsu et al. (1992) demonstrated that the GALNS gene is located on chromosome 16q24 by fluorescence in situ hybridization. Baker et al. (1993), also using fluorescence in situ hybridization, mapped the gene to 16q24.3. The authors also confirmed the localization to this band by PCR analysis of the somatic cell hybrid panel used for fine mapping of chromosome 16. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In patients with mucopolysaccharidosis type IVA (253000), also known as Morquio syndrome A, Tomatsu et al. (1992) identified 4 different mutations in the GALNS gene (612222.0001-612222.0004).</p><p>In 5 unrelated Japanese patients with MPS IVA, Hori et al. (1995) found, in heteroallelic state, 2 separate deletions of nearly 8.0 and 6.0 kb in the GALNS gene. There were Alu repetitive elements near the breakpoints of the 8.0-kb deletion; this deletion had clearly resulted from an Alu-Alu recombination. The 6.0-kb deletion involved illegitimate recombinational events between incomplete short direct repeats of 8 bp at the deletion breakpoints. This was the first documentation of a frequently occurring double deletion in a gene that is not a member of a gene cluster. One of the patients was homozygous for the double deletion, and the others were heterozygous. In the 4 who were heterozygous, Tomatsu et al. (1996) identified novel mutations in the GALNS gene on the other allele: 1 nonsense and 3 missense. </p><p>Wang et al. (2010) identified 27 GALNS mutations, including 16 novel mutations, among 24 Chinese patients with MPS IVA. Approximately 63% of the mutations found among the Chinese patients were not observed in other countries, suggesting that a different mutational spectrum may exist in the Chinese population. The most common mutation G340D (612222.0018) was present in 8 (16.7%) of 48 mutant alleles and was found only in 5 patients from central eastern China. Haplotype analysis indicated a founder effect. </p><p>Caciotti et al. (2015) studied 37 Italian MPS IVA patients and found that standard sequencing procedures failed to characterize the second disease-causing mutation in 16 percent of patients. Searching for large rearrangements and mRNA defects in this 16% identified splicing defects or large deletions on the other allele in 67% of these. Caciotti et al. (2015) reported 14 novel mutations in GALNS among the 37 patients. </p>
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|
</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
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</span>
|
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Sukegawa et al. (2000) studied 15 missense mutations and 2 newly engineered active site mutations (C79S, C79T) in the GALNS gene by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms, while the C79S and C79T mutants were of a soluble mature size. Mutations identified in patients with the severe phenotype had no activity, whereas mutations identified in patients with the mild phenotype had a considerable residual activity (1.3-13.3% of wildtype GALNS activity). Sukegawa et al. (2000) also constructed a tertiary structural model of human GALNS from the x-ray crystal structure of homologous sulfatases and investigated 32 missense mutations. The authors proposed 3 different biochemical models for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. </p>
|
|
</span>
|
|
<div>
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|
<br />
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|
</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Tomatsu et al. (2003) generated transgenic mice homozygous for a disruption in exon 2 of the Galns gene. These mice had no detectable GALNS enzyme activity, showed increased urinary glycosaminoglycan levels, and accumulated glycosaminoglycans in multiple tissues including liver, kidney, spleen, heart, brain, and bone marrow. At 2 months old, lysosomal storage was present primarily within reticuloendothelial cells. By 12 months old, vacuolar change was observed in glomeruli and heart valves. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage, and keratan sulfate and chondroitin-6-sulfate were more abundant in corneal epithelial cells of Galns -/- mice. Surprisingly, radiographs revealed no change in the skeletal bones of mice up to 12 months old. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>18 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
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|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
GALNS, ASN204LYS
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|
<br />
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|
SNP: rs118204435,
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|
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|
|
ClinVar: RCV000000733
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|
|
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|
</span>
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|
</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In 2 brothers with a mild form of Morquio syndrome A (253000), Fukuda et al. (1992) and Tomatsu et al. (1992) identified a homozygous 667C-G transversion in the GALNS gene, resulting in an asn204-to-lys (N204K) substitution. Both unaffected parents were heterozygous for the mutation. Transient expression of the mutant allele in GALNS-deficient fibroblasts showed markedly decreased enzyme activity. </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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|
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|
<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
GALNS, ALA138VAL
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|
<br />
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|
SNP: rs118204436,
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|
|
ClinVar: RCV000000734
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a severe form of Morquio syndrome A (253000), Tomatsu et al. (1992) identified a homozygous 468T-C transition in the GALNS gene, resulting in an ala138-to-val (A138V) substitution.</p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
<div>
|
|
<span class="mim-text-font">
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|
|
|
GALNS, ARG386CYS
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|
<br />
|
|
|
|
SNP: rs118204437,
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|
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|
|
|
gnomAD: rs118204437,
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|
|
|
|
|
ClinVar: RCV000000735, RCV000079019, RCV000781397
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe Morquio syndrome A (253000), Tomatsu et al. (1992) identified a 386C-T transition in the GALNS gene, resulting in an arg386-to-cys (R386C) substitution. A PCR method was used for complete cDNA sequencing.</p><p>In a study of 20 MPS IVA patients from Latin America, including 16 with a severe phenotype and 4 with an attenuated phenotype, Tomatsu et al. (2004) identified 12 different mutations in the GALNS gene, 9 of which were previously unreported. The R386C mutation accounted for 32.5% of the unrelated mutant alleles. It was identified in all the Latin American populations studied and was associated with a severe form of the disorder. MPS IVA patients had increased urine and plasma keratan sulfate concentrations compared to normal controls. Keratan sulfate concentrations were higher in patients with a severe phenotype than in those with the attenuated form of the disorder. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, 2-BP DEL, 1343CA
|
|
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|
|
<br />
|
|
|
|
SNP: rs2142992359,
|
|
|
|
|
|
|
|
ClinVar: RCV001578607
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient, born of consanguineous parents, with a severe form of Morquio syndrome A (253000), Fukuda et al. (1992) and Tomatsu et al. (1992) identified a homozygous 2-bp deletion in the GALNS gene (1343delCA). Fukuda et al. (1992) referred to the mutation as 1342delCA. This mutation was revealed by TaqI restriction analysis of a cDNA fragment amplified by the polymerase chain reaction. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, ILE113PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204438,
|
|
|
|
|
|
gnomAD: rs118204438,
|
|
|
|
|
|
ClinVar: RCV000000738, RCV000295527, RCV000723431
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Caucasian patients with Morquio syndrome A (253000), Tomatsu et al. (1995) identified a 393A-T transversion in the GALNS gene, resulting in an ile113-to-phe (I113F) substitution. Allele-specific oligonucleotide (ASO) or SSCP analysis indicated that this mutation accounted for 9 (22.5%) of 40 unrelated mutant chromosomes from 23 Caucasian patients, including 6 consanguineous cases. It was not found among 20 Japanese patients. In addition to this common mutation, 10 different point mutations and 2 small deletions were detected. </p><p>Among 23 Australian or Irish patients with Morquio syndrome A and various clinical phenotypes, Yamada et al. (1998) found that the I113F mutation was associated with a severe phenotype. The relative frequency of the I113F mutation in Australia corresponded to that observed in Northern Ireland, suggesting that both mutations were probably introduced to Australia by Irish migrants during the 19th century. Haplotype analysis provided additional data that the I113F mutation originated from a common ancestor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, GLN473TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204439,
|
|
|
|
|
|
gnomAD: rs118204439,
|
|
|
|
|
|
ClinVar: RCV000000739
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe Morquio disease (253000), Tomatsu et al. (1995) identified compound heterozygosity for 2 mutations in exon 13 of the GALNS gene: a C-to-T transition resulting in a gln473-to-ter (Q473X) substitution, and an A-to-G transition resulting in an asn487-to-ser substitution (N487S; 612222.0007). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, ASN487SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204440,
|
|
|
|
|
|
|
|
ClinVar: RCV000000736
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0006 and Tomatsu et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, ARG94GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204441,
|
|
|
|
|
|
gnomAD: rs118204441,
|
|
|
|
|
|
ClinVar: RCV000000740
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Polish sibs with Morquio syndrome (253000), Bunge et al. (1997) identified compound heterozygosity for 2 mutations in the GALNS gene: an arg94-to-gly (R94G) substitution inherited from the father and an arg259-to-gln (R259Q; 612222.0009) substitution inherited from the mother. The sibs were diagnosed at 5 and 6 years of age, respectively. At ages 13 and 14, they were still considered to be mildly affected, with mild thoracolumbar kyphosis, slight prominence of the sternum, hypermobility of ligaments, hip hypoplasia in the boy only, no corneal clouding, and normal height. Their mother, who was homozygous for the R259Q mutation, was found to have greatly reduced enzymatic activity, but only limited manifestations of MPS IVA: short trunk with slight prominence of sternum, and hoarse voice. She had no corneal clouding and was 1.60 m tall. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, ARG259GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204442,
|
|
|
|
|
|
gnomAD: rs118204442,
|
|
|
|
|
|
ClinVar: RCV000000741, RCV004777560
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0008 and Bunge et al. (1997). </p><p>Tylki-Szymanska et al. (1998) described a 2-generation Morquio A (253000) family with 2 distinct clinical phenotypes. The 2 probands from the second generation showed intermediate signs of the disease, whereas their affected mother, aunt, and 2 uncles had only very mild symptoms. Galactose-6-sulfatase activity in leukocytes and fibroblasts of the affected family members was clearly deficient. Molecular genetic analysis of the GALNS gene showed that 2 different point mutations segregated in the family and correlated well with the clinical phenotype. The probands with intermediate severity of symptoms were compound heterozygous for the R94G mutation (612222.0008), which was inherited from the unaffected father, and for R259Q. The mother and her affected sibs with the unusually mild phenotype were homozygous for the R259Q mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, GLY301CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204443,
|
|
|
|
|
|
gnomAD: rs118204443,
|
|
|
|
|
|
ClinVar: RCV000000743, RCV000781400, RCV000790840
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kato et al. (1997) identified 3 novel missense mutations in 16 of 19 Colombian Morquio syndrome A unrelated alleles (84.2%). A gly301-to-cys (G301C) mutation and a S162F (612222.0011) mutation accounted for 68.4% and 10.5% of mutations, respectively, whereas the third mutation, F69V, (612222.0012), was limited to a single allele. The skewed prevalence of G301C in Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggested that G301C originated from a common ancestor. Investigation of a genetic background by means of mtDNA lineages indicated that all of the Colombian patients were probably of Native American descent. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, SER162PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204444,
|
|
|
|
|
|
gnomAD: rs118204444,
|
|
|
|
|
|
ClinVar: RCV000000744, RCV000723452
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0010 and Kato et al. (1997). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, PHE69VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204445,
|
|
|
|
|
|
|
|
ClinVar: RCV000000745
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0010 and Kato et al. (1997). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</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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GALNS, THR312SER
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<br />
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SNP: rs118204446,
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gnomAD: rs118204446,
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|
|
ClinVar: RCV000000748, RCV001193737
|
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|
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Studies of patients from the British-Irish population have shown that the I113F (612222.0005) mutation in the GALNS gene is the most common single mutation among Morquio syndrome A patients and produces a severe clinical phenotype. Yamada et al. (1998) studied mutations in the GALNS gene from 23 additional patients (15 from Australia, 8 from Northern Ireland) with various clinical phenotypes (severe, 16 cases; intermediate, 4 cases; mild, 3 cases). They found 2 common mutations that together accounted for 32% of the 44 unrelated alleles in these patients. One was a thr312-to-ser (T312S) substitution, found exclusively in milder patients, and the other was I113F, which produced a severe phenotype. Relatively high residual GALNS activity seen when the T312S mutant cDNA was overexpressed in mutant cells provided an explanation for the mild phenotype in patients with this mutation. The disruption and relative frequency of the I113F and T312S mutations in Australia corresponded to those observed in Northern Ireland and were unique to these 2 populations, suggesting that both mutations were probably introduced to Australia by Irish migrants during the 19th century. Haplotype analysis provided additional data that the I113F mutation originated from a common ancestor. The other 9 novel mutations identified in these 23 patients were each limited to a single family. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUCOPOLYSACCHARIDOSIS, TYPE IVA</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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|
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GALNS, ASP60ASN
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<br />
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SNP: rs118204447,
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gnomAD: rs118204447,
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ClinVar: RCV000000749
|
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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>Montano et al. (2003) described the clinical phenotype of 5 patients from 3 unrelated Finnish families with Morquio A disease and characterized the disease-causing mutations in GALNS. In all 3 families the affected individuals were compound heterozygous for an asp60-to-asn (D60N) mutation and a second mutation: A291T (612222.0015) and W230X (612222.0016) in 2 of the families, and 1374delT (612222.0017) causing premature termination in a third. W230X and A291T had no residual GALNS activity when overexpressed in cultured cells, whereas D60N had 12.2% residual activity compared with wildtype. The tertiary structural model of the GALNS protein showed that asp60 is located on the surface of the molecule, away from the active site. On the other hand, ala291 and trp230 are localized near the active site. The molecular characteristics of the D60N mutation explained the attenuated clinical phenotype of the patients. The oldest patient was 9 years of age, and the youngest 3 years. </p>
|
|
</span>
|
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</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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GALNS, ALA291THR
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<br />
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|
|
SNP: rs118204448,
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|
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|
|
ClinVar: RCV000000742, RCV003234884
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0014 and Montano et al. (2003). </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
GALNS, TRP230TER
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<br />
|
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|
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SNP: rs118204449,
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|
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ClinVar: RCV000000746, RCV001193132
|
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|
|
</span>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0014 and Montano et al. (2003). </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>.0017 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, 1-BP DEL, 1374T
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|
|
<br />
|
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|
|
SNP: rs1567517083,
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|
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|
|
|
ClinVar: RCV001578608
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 612222.0014 and Montano et al. (2003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 MUCOPOLYSACCHARIDOSIS, TYPE IVA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALNS, GLY340ASP
|
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|
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|
|
<br />
|
|
|
|
SNP: rs267606838,
|
|
|
|
|
|
|
|
ClinVar: RCV000000750, RCV003155036
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 of 24 Chinese patients with MPS IVA (253000), Wang et al. (2010) identified a 1019G-A transition in exon 10 of the GALNS gene, resulting in a gly340-to-asp (G340D) substitution. Three patients were homozygous, and 2 patients were compound heterozygous for G340D and another mutation. G340D was the most common mutant allele, accounting for 16.7% of the total number of mutant alleles. Haplotype analysis indicated a founder effect, and all 5 patients were residents of or emigrants from central eastern China. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Masuno et al. (1993)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baker, E., Guo, X.-H., Orsborn, A. M., Sutherland, G. R., Callen, D. F., Hopwood, J. J., Morris, C. P.
|
|
<strong>The Morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3.</strong>
|
|
Am. J. Hum. Genet. 52: 96-98, 1993.
|
|
|
|
|
|
[PubMed: 8434612]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bunge, S., Kleijer, W. J., Tylki-Szymanska, A., Steglich, C., Beck, M., Tomatsu, S., Fukuda, S., Poorthuis, B. J. H. M., Czartoryska, B., Orii, T., Gal, A.
|
|
<strong>Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.</strong>
|
|
Hum. Mutat. 10: 223-232, 1997.
|
|
|
|
|
|
[PubMed: 9298823]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caciotti, A., Tonin, R., Rigoldi, M., Ferri, L., Catarzi, S., Cavicchi, C., Procopio, E., Donati, M. A., Ficcadenti, A., Fiumara, A., Barone, R., Garavelli, L., and 16 others.
|
|
<strong>Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio--A syndrome-associated mutations.</strong>
|
|
Hum. Mutat. 36: 357-368, 2015.
|
|
|
|
|
|
[PubMed: 25545067]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22751]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukuda, S., Tomatsu, S., Masue, M., Sukegawa, K., Iwata, H., Ogawa, T., Nakashima, Y., Hori, T., Yamagishi, A., Hanyu, Y., Morooka, K., Kiman, T., Hashimoto, T., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.</strong>
|
|
J. Clin. Invest. 90: 1049-1053, 1992.
|
|
|
|
|
|
[PubMed: 1522213]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115919]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, G. J., Saccone, G. T. P., Brooks, D. A., Clements, P. R., Hopwood, J. J.
|
|
<strong>Human N-acetylgalactosamine-4-sulphate sulphatase: purification, monoclonal antibody production and native and subunit M(r) values.</strong>
|
|
Biochem. J. 248: 755-764, 1987.
|
|
|
|
|
|
[PubMed: 3435483]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bj2480755]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hori, T., Tomatsu, S., Nakashima, Y., Uchiyama, A., Fukuda, S., Sukegawa, K., Shimozawa, N., Suzuki, Y., Kondo, N., Horiuchi, T., Ogura, S., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: common double deletion in the N-acetylgalactosamine-6-sulfatase gene (GALNS).</strong>
|
|
Genomics 26: 535-542, 1995.
|
|
|
|
|
|
[PubMed: 7607677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80172-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kato, Z., Fukuda, S., Tomatsu, S., Vega, H., Yasunaga, T., Yamagishi, A., Yamada, N., Valencia, A., Barrera, L. A., Sukegawa, K., Orii, T., Kondo, N.
|
|
<strong>A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.</strong>
|
|
Hum. Genet. 101: 97-101, 1997.
|
|
|
|
|
|
[PubMed: 9385378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050594]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Masuno, M., Tomatsu, S., Nakashima, Y., Hori, T., Fukuda, S., Masue, M., Sukegawa, K., Orii, T.
|
|
<strong>Mucopolysaccharidosis IV A: assignment of the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene to chromosome 16q24.</strong>
|
|
Genomics 16: 777-778, 1993.
|
|
|
|
|
|
[PubMed: 8325655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1266]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montano, A. M., Kaitila, I., Sukegawa, K., Tomatsu, S., Kato, Z., Nakamura, H., Fukuda, S., Orii, T., Kondo, N.
|
|
<strong>Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype.</strong>
|
|
Hum. Genet. 113: 162-169, 2003.
|
|
|
|
|
|
[PubMed: 12721840]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-003-0959-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morris, C. P., Guo, X.-H., Apostolou, S., Hopwood, J. J., Scott, H. S.
|
|
<strong>Morquio A syndrome: cloning, sequence, and structure of the human N-acetylgalactosamine 6-sulfatase (GALNS) gene.</strong>
|
|
Genomics 22: 652-654, 1994.
|
|
|
|
|
|
[PubMed: 8001980]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakashima, Y., Tomatsu, S., Hori, T., Fukuda, S., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5-prime-flanking region.</strong>
|
|
Genomics 20: 99-104, 1994.
|
|
|
|
|
|
[PubMed: 8020961]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1132]
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sukegawa, K., Nakamura, H., Kato, Z., Tomatsu, S., Montano, A. M., Fukao, T., Toietta, G., Tortora, P., Orii, T., Kondo, N.
|
|
<strong>Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.</strong>
|
|
Hum. Molec. Genet. 9: 1283-1290, 2000.
|
|
|
|
|
|
[PubMed: 10814710]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.9.1283]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Dieter, T., Schwartz, I. V., Sarmient, P., Giugliani, R., Barrera, L. A., Guelbert, N., Kremer, R., Repetto, G. M., Gutierrez, M. A., Nishioka, T., Serrato, O. P., Montano, A. M., Yamaguchi, S., Noguchi, A.
|
|
<strong>Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate.</strong>
|
|
J. Hum. Genet. 49: 490-494, 2004.
|
|
|
|
|
|
[PubMed: 15309681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-004-0178-8]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Rezvi, G. M. M., Yamagishi, A., Yamada, N., Kato, Z., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-acetylgalactosamine-6-sulfate sulfatase gene.</strong>
|
|
Am. J. Hum. Genet. 57: 556-563, 1995.
|
|
|
|
|
|
[PubMed: 7668283]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Cooper, A., Wraith, J. E., Yamada, N., Isogai, K., Kato, Z., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease).</strong>
|
|
Hum. Mutat. 6: 195-196, 1995.
|
|
|
|
|
|
[PubMed: 7581409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380060218]
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Fukao, T., Yamagishi, A., Hori, T., Iwata, H., Ogawa, T., Nakashima, Y., Hanyu, Y., Hashimoto, T., Titani, K., Oyama, R., Suzuki, M., Yagi, K., Hayashi, Y., Orii, T.
|
|
<strong>Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 677-683, 1991.
|
|
|
|
|
|
[PubMed: 1755850]
|
|
|
|
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[Full Text: https://doi.org/10.1016/0006-291x(91)91244-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
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Tomatsu, S., Fukuda, S., Masue, M., Sukegawa, K., Masuno, M., Orii, T.
|
|
<strong>Mucopolysaccharidosis type IVA: characterization and chromosomal localization of N-acetylgalactosamine-6-sulfate sulfatase gene and genetic heterogeneity. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A178, 1992.
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Tomatsu, S., Fukuda, S., Yamagishi, A., Cooper, A., Wraith, J. E., Hori, T., Kato, Z., Yamada, N., Isogai, K., Sukegawa, K., Kondo, N., Suzuki, Y., Shimozawa, N., Orii, T.
|
|
<strong>Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.</strong>
|
|
Am. J. Hum. Genet. 58: 950-962, 1996.
|
|
|
|
|
|
[PubMed: 8651279]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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Tomatsu, S., Orii, K. O., Vogler, C., Nakayama, J., Levy, B., Grubb, J. H., Gutierrez, M. A., Shim, S., Yamaguchi, S., Nishioka, T., Montano, A. M., Noguchi, A., Orii, T., Kondo, N., Sly, W. S.
|
|
<strong>Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease.</strong>
|
|
Hum. Molec. Genet. 12: 3349-3358, 2003.
|
|
|
|
|
|
[PubMed: 14583446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg366]
|
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</p>
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</li>
|
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|
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<li>
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Tylki-Szymanska, A., Czartoryska, B., Bunge, S., van Diggelen, O. P., Kleijer, W. J., Poorthuis, B. J. H. M., Huijmans, J. G. M., Gorska, D.
|
|
<strong>Clinical, biochemical and molecular findings in a two-generation Morquio A family.</strong>
|
|
Clin. Genet. 53: 369-374, 1998.
|
|
|
|
|
|
[PubMed: 9660054]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1998.tb02747.x]
|
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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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Wang, Z., Zhang, W., Wang, Y., Meng, Y., Su, L., Shi, H., Huang, S.
|
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<strong>Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.</strong>
|
|
J. Hum. Genet. 55: 534-540, 2010.
|
|
|
|
|
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[PubMed: 20574428]
|
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[Full Text: https://doi.org/10.1038/jhg.2010.65]
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</p>
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</li>
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Yamada, N., Fukuda, S., Tomatsu, S., Muller, V., Hopwood, J. J., Nelson, J., Kato, Z., Yamagishi, A., Sukegawa, K., Kondo, N., Orii, T.
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|
<strong>Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.</strong>
|
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Hum. Mutat. 11: 202-208, 1998.
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[PubMed: 9521421]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J]
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