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Entry
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- *606882 - ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B
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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">*606882</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</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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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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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/606882">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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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=ENSG00000123191;t=ENST00000242839" 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=540" 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=606882" 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=ENSG00000123191;t=ENST00000242839" 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_000053,NM_001005918,NM_001243182,NM_001330578,NM_001330579,NM_001406511,NM_001406512,NM_001406513,NM_001406514,NM_001406515,NM_001406516,NM_001406517,NM_001406518,NM_001406519,NM_001406520,NM_001406521,NM_001406522,NM_001406523,NM_001406524,NM_001406525,NM_001406526,NM_001406527,NM_001406528,NM_001406530,NM_001406531,NM_001406532,NM_001406534,NM_001406535,NM_001406536,NM_001406537,NM_001406538,NM_001406539,NM_001406540,NM_001406541,NM_001406542,NM_001406543,NM_001406544,NM_001406545,NM_001406546,NM_001406547,NM_001406548" 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_000053" 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=606882" 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=06050&isoform_id=06050_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/ATP7B" 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/409358,452075,452076,551502,957353,957355,1947035,4104338,4262839,6707655,6746629,6752899,7001392,7001394,7689040,7689042,7689044,9587125,9587126,11037261,11037263,11037265,11037267,11037269,11037271,55743071,55743073,62088502,62510242,62510246,62510248,62510253,62510255,64174737,109658984,119629297,119629298,119629299,119629300,119629301,119722350,148767911,151303110,151303113,154818216,156076380,194378596,194379618,219518083,219519483,219520121,224812797,239938919,256028970,284927860,284927862,339516609,339516611,339516613,339516615,339516617,339516619,342187274,354683507,526482177,1060085920,1060085922,1423658844,1423658846,1423658848,1423658850,1423658852,1423658854,1423658856,1777420219,1777420221,1777420223,1777420225,1777420227,1777420229,1777420231,1777420233,1777420235,1777420237,1777420239,1777420241,1896097968,1896097970,1896097972,1896097974,1896097976,1896097978,1896097980,1896097982,1896097984,1896097986,1896097988,1896097990,1896097992,1896097994,1896097996,1896097998,1896098000,1896098002,1896098004,1896098006,1896098008,1896098010,1896098012,1896098014,1896098016,1896098018,1896098020,1896098022,1896098024,1896098026,1896098028,1896098030,1896098032,1896098034,1896098036,1896098038,1896098040,1896098042,1896098044,1896098046,1896098048,1896098050,1896098052,1896098054,1896098056,1896098058,1896098060,1896098062,1896098064,1896098066,1896098068,1896098070,1896098072,1896098074,1896098076,1896098078,1896098080,1896098082,1896098084,1896098086,1896098088,1896098090,1896098092,1896098094,1896098096,1896098098,1896098100,1896098102,1896098104,1896098106,1896098108,1896098110,2131581230,2131581232,2131581234,2131581236,2131581238,2240200033,2240200035,2240200037,2240200041,2240200050,2240200065,2240200072,2240200082,2240200084,2240200089,2240200101,2240200109,2240200118,2240200121,2240200128,2240200131,2240200133,2240200135,2240200139,2240200141,2240200148,2240200159,2240200167,2240200169,2240200171,2240200178,2240200188,2240200190,2240200194,2240200196,2240200198,2240200204,2240200206,2240200216,2240200219,2240207793" 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/P35670" 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=540" 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=ENSG00000123191;t=ENST00000242839" 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=ATP7B" 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=ATP7B" 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+540" 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/ATP7B" 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:540" 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/540" 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=chr13&hgg_gene=ENST00000242839.10&hgg_start=51932669&hgg_end=52012132&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:870" 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:870" 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/atp7b" 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=606882[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=606882[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/ATP7B/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000123191" 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=ATP7B" 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=ATP7B" 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=ATP7B" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.umd.be/ATP7B/" title="The UMD ATP7B mutations database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The UMD ATP7B mutations da…</a></div><div style="margin-left: 0.5em;"><a href="http://www.wilsondisease.med.ualberta.ca/database.asp" title="Wilson Disease Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Wilson Disease Mutation Da…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ATP7B&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/PA73" 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:870" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0030343.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:103297" 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/ATP7B#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:103297" 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/540/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA001071/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=540" 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=WBGene00000834;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-061220-5" 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:540" 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=ATP7B&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> 190823004, 88518009<br />
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<strong>ICD10CM:</strong> E83.01<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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606882
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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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ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B
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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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ATPase COPPER TRANSPORTING BETA<br />
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WND
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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=ATP7B" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ATP7B</a></em></strong>
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</span>
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</p>
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</div>
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Cytogenetic location: <a href="/geneMap/13/192?start=-3&limit=10&highlight=192">13q14.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:51932669-52012132&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'})">13:51,932,669-52,012,132</a> </span>
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Wilson disease
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<a href="/entry/277900"> 277900 </a>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/606882" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/606882" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>The ATP7B gene encodes a polypeptide that acts as a plasma membrane copper-transport protein (summary by <a href="#15" class="mim-tip-reference" title="Harris, E. D. <strong>Cellular copper transport and metabolism.</strong> Annu. Rev. Nutr. 20: 291-310, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10940336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10940336</a>] [<a href="https://doi.org/10.1146/annurev.nutr.20.1.291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10940336">Harris, 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10940336" 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>On YACs from the 13q14.3 region, <a href="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a> identified a sequence similar to that coding for the proposed copper-binding regions of the putative ATPase gene defective in Menkes disease (MNK; <a href="/entry/309400">309400</a>). They showed that this sequence forms part of a P-type ATPase gene that is very similar to MNK, with 6 putative metal-binding regions similar to those found in prokaryotic heavy metal transporters. The gene, designated ATP7B, is expressed in liver and kidney, and was found to lie within a 300-kb region likely to include the Wilson disease locus (WND; <a href="/entry/277900">277900</a>). The identity between MNK and the newly identified ATP7B gene was 78% in the transduction region, 89% in the channel/phosphorylation regions, and 79% in the ATP-binding region. The predicted length of the gene product was 1,411 amino acids for ATP7B compared with 1,500 amino acids for MNK. The overall identity between the two was 57%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" 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="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> used consensus DNA sequences for heavy metal binding motifs to identify homologous cDNA clones. One of these was mapped by PCR amplification and Southern blotting to contiguous YAC and cosmid clones that span the WND locus at chromosome 13q14.3. The cDNA detected a 7.5-kb RNA transcript expressed most strongly in liver and brain. Sequence analysis indicated several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. The deduced protein showed 62% amino acid homology to the Menkes disease gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" 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="#48" class="mim-tip-reference" title="Yang, X.-L., Miura, N., Kawarada, Y., Terada, K., Petrukhin, K., Gilliam, T. C., Sugiyama, T. <strong>Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.</strong> Biochem. J. 326: 897-902, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9307043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9307043</a>] [<a href="https://doi.org/10.1042/bj3260897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9307043">Yang et al. (1997)</a> stated that the full-length ATP7B protein contains 1,465 amino acids. They cloned a splice variant of ATP7B lacking exons 6, 7, 8, and 12 from a human brain cDNA library. The deduced protein contains 1,258 amino acids. Immunofluorescence localization and fractionation of a hepatoma cell line revealed that the full-length protein was associated with the Golgi apparatus and the shorter isoform was cytosolic. Full-length ATP7B did not redistribute in response to elevated copper levels, and it did not associate with the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9307043" 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="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> noted that the protein encoded by the ATP7B gene had the characteristics of a copper-transporting ATPase. They suggested that it may serve a function in the export of copper from cells, whereas the Menkes gene product has a role in the import of copper. <a href="#5" class="mim-tip-reference" title="Dijkstra, M., In't Veld, G., van den Berg, G. J., Muller, M., Kuipers, F., Vonk, R. J. <strong>Adenosine triphosphate-dependent copper transport in isolated rat liver plasma membranes.</strong> J. Clin. Invest. 95: 412-416, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7814642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7814642</a>] [<a href="https://doi.org/10.1172/JCI117670" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7814642">Dijkstra et al. (1995)</a> studied copper transport in rat liver plasma membranes and suggested that the ATP7B protein functions to transport copper across these membranes in the presence of ATP. <a href="#15" class="mim-tip-reference" title="Harris, E. D. <strong>Cellular copper transport and metabolism.</strong> Annu. Rev. Nutr. 20: 291-310, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10940336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10940336</a>] [<a href="https://doi.org/10.1146/annurev.nutr.20.1.291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10940336">Harris (2000)</a> reviewed cellular copper transport and metabolism and stated that the ATP7B protein resides within internal compartments of the cell, where it may function to incorporate copper into apo-ceruloplasmin, and to release copper into bile. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7814642+10940336+8298641" 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="Lim, C. M., Cater, M. A., Mercer, J. F. B., La Fontaine, S. <strong>Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A.</strong> J. Biol. Chem. 281: 14006-14014, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554302</a>] [<a href="https://doi.org/10.1074/jbc.M512745200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16554302">Lim et al. (2006)</a> stated that ATP7B localizes to the trans-Golgi network, where it transports copper to apoceruloplasmin (CP; <a href="/entry/117700">117700</a>). When copper levels are in excess, ATP7B redistributes to a vesicular compartment near the biliary canalicular membranes for elimination of excess copper into bile. Using a yeast 2-hybrid screen of a human liver cDNA library, <a href="#20" class="mim-tip-reference" title="Lim, C. M., Cater, M. A., Mercer, J. F. B., La Fontaine, S. <strong>Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A.</strong> J. Biol. Chem. 281: 14006-14014, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554302</a>] [<a href="https://doi.org/10.1074/jbc.M512745200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16554302">Lim et al. (2006)</a> found that the N-terminal domain of ATP7B, which contains 6 metal-binding motifs, interacted with the C-terminal domain of the p62 dynactin subunit (DCTN4; <a href="/entry/614758">614758</a>). Coimmunoprecipitation analysis revealed that ATP7B, but not ATP7A (<a href="/entry/300011">300011</a>), interacted with endogenous p62 in a human fibroblast line. Depletion of copper reduced interaction of ATP7B with p62. Mutation analysis revealed that the metal-binding CxxC motifs of ATP7B were required for interaction with p62, predominantly CxxC motifs 4 through 6. <a href="#20" class="mim-tip-reference" title="Lim, C. M., Cater, M. A., Mercer, J. F. B., La Fontaine, S. <strong>Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A.</strong> J. Biol. Chem. 281: 14006-14014, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554302</a>] [<a href="https://doi.org/10.1074/jbc.M512745200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16554302">Lim et al. (2006)</a> concluded that ATP7B is transported along liver cell microtubules in a copper-dependent manner via interaction with the p62 dynactin subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16554302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Variant Proteins</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Forbes, J. R., Cox, D. W. <strong>Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.</strong> Hum. Molec. Genet. 9: 1927-1935, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942420</a>] [<a href="https://doi.org/10.1093/hmg/9.13.1927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10942420">Forbes and Cox (2000)</a> analyzed the intracellular localization of ATP7B variant proteins using transient transfection and triple-label immunofluorescence microscopy. Two human WND ATP7B variants, asp765 to asn (<a href="#0012">606882.0012</a>) and leu776 to val, which have normal copper transport activity in yeast, retained partial normal Golgi network localization, but were predominantly mislocalized throughout the cell and were capable of only partial copper-dependent redistribution. Variant protein arg778 to leu (R778L; <a href="#0009">606882.0009</a>), which has defective function in yeast, was extensively mislocalized, presumably to the endoplasmic reticulum. Variant proteins gly943 to ser (<a href="#0013">606882.0013</a>), which has nearly normal function in yeast, and cys-pro-cys/ser (mutation of the conserved cys-pro-cys motif to ser-pro-ser), which is inactive in yeast, were localized normally but were unable to redistribute in response to copper. The authors hypothesized that mislocalization and/or deficient copper transport are defects seen in some mutant proteins, and that the nature of the malfunction(s) may explain, in part, the variable biochemical features of WND, in particular the normal holoceruloplasmin levels observed in some patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="La Fontaine, S., Theophilos, M. B., Firth, S. D., Gould, R., Parton, R. G., Mercer, J. F. B. <strong>Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase.</strong> Hum. Molec. Genet. 10: 361-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11157799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11157799</a>] [<a href="https://doi.org/10.1093/hmg/10.4.361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11157799">La Fontaine et al. (2001)</a> generated cDNA constructs encoding the wildtype (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) and expressed them in Chinese hamster ovary (CHO) cells. The tx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, colocalization experiments demonstrated that while Wnd and MNK (<a href="/entry/309400">309400</a>) are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell. Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multivesicular structures resembling late endosomes that may represent a novel compartment for copper transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11157799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Luoma, L. M., Deeb, T. M., Macintyre, G., Cox, D. W. <strong>Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.</strong> Hum. Mutat. 31: 569-577, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20333758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20333758</a>] [<a href="https://doi.org/10.1002/humu.21228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20333758">Luoma et al. (2010)</a> generated yeast deficient in Ccc2, the ortholog of ATP7B, and used the Ccc2-deficient yeast model system to test the functional effect of 12 ATP7B missense variants that localize to the ATP loop of the protein. These variants may affect binding of ATP, autophosphorylation, or folding of the protein. Variants L1043P, G1000R, G1101R, I1102T, V1239G, and D1267V were found to be deleterious; G1176E and G1287S were intermediate; E1173G were temperature-sensitive; and T991M and I1148T were mild. The R1228T variant functioned similar to wildtype protein. Comparison of the functional data from the yeast model system with 3 predictive programs indicated that SIFT was most accurate (92%) followed by PolyPhen (83%) and Align-GVGD (67%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20333758" 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="#48" class="mim-tip-reference" title="Yang, X.-L., Miura, N., Kawarada, Y., Terada, K., Petrukhin, K., Gilliam, T. C., Sugiyama, T. <strong>Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.</strong> Biochem. J. 326: 897-902, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9307043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9307043</a>] [<a href="https://doi.org/10.1042/bj3260897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9307043">Yang et al. (1997)</a> determined that the ATP7B gene contains 21 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9307043" 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="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a> identified the ATP7B gene in the Wilson disease critical region on chromosome 13q14.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" 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="#35" class="mim-tip-reference" title="Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N. <strong>The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.</strong> Biochem. Biophys. Res. Commun. 202: 512-518, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8037756</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8037756">Sasaki et al. (1994)</a> identified the rat homolog of the human Wilson disease gene as the gene responsible for hepatitis (hts) in the Long Evans Cinnamon rat. They mapped the rat Wnd gene to 16q12.23-q12.3 by fluorescence in situ hybridization and mouse/rat somatic cell hybrid analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8037756" 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="#34" class="mim-tip-reference" title="Reed, V., Williamson, P., Bull, P. C., Cox, D. W., Boyd, Y. <strong>Mapping of the mouse homologue of the Wilson disease gene to mouse chromosome 8.</strong> Genomics 28: 573-575, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490097</a>] [<a href="https://doi.org/10.1006/geno.1995.1191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490097">Reed et al. (1995)</a> mapped the homolog of ATP7B to mouse chromosome 8 by somatic cell hybrid analysis. Interspecific backcross analysis showed that Atp7b is close to D8Mit3 and Atp4b, another ATPase gene. Interestingly, human ATP7B occurs in a region of conserved synteny with mouse chromosome 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490097" 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="#11" class="mim-tip-reference" title="Gourdon, P., Liu, X.-Y., Skjorringe, T., Morth, J. P., Moller, L. B., Pedersen, B. P., Nissen, P. <strong>Crystal structure of a copper-transporting PIB-type ATPase.</strong> Nature 475: 59-64, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21716286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21716286</a>] [<a href="https://doi.org/10.1038/nature10191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21716286">Gourdon et al. (2011)</a> presented the structure of a P-type class IB (PIB) ATPase, a Legionella pneumophila CopA copper ATPase, in a copper-free form, as determined by x-ray crystallography at 3.2-angstrom resolution. The structure indicates a 3-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to calcium ATPase suggested an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. <a href="#11" class="mim-tip-reference" title="Gourdon, P., Liu, X.-Y., Skjorringe, T., Morth, J. P., Moller, L. B., Pedersen, B. P., Nissen, P. <strong>Crystal structure of a copper-transporting PIB-type ATPase.</strong> Nature 475: 59-64, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21716286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21716286</a>] [<a href="https://doi.org/10.1038/nature10191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21716286">Gourdon et al. (2011)</a> suggested that their structure will provide a framework for analysis of missense mutations in human ATP7A and ATP7B proteins associated with Menkes disease and Wilson disease, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21716286" 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="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a> reported 2 patients with Wilson disease (WND; <a href="/entry/277900">277900</a>) who were found to be homozygous for a 7-bp deletion within the coding region of the ATP7B gene (<a href="#0001">606882.0001</a>). <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> noted that a lysine-to-arginine mutation near the phosphorylation site of the ATPase occurred in 85% of all WND chromosomes analyzed and in only 15% of 'normal' chromosomes in diverse populations. <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> identified 4 mutations in unrelated persons with Wilson disease: 2 missense mutations and 2 frameshift mutations resulting in a truncated gene product (<a href="#0002">606882.0002</a>-<a href="#0005">606882.0005</a>). The mutations were found among 50 unrelated families derived predominantly from the United States, 18 unrelated families from Russia, and 5 presumably unrelated families from Sicily. Clearly, <a href="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a> and <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> had independently isolated the same gene which was convincingly the one mutant in Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8298641+8298639" 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="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> reviewed the mutations found in the ATP7B gene. In 58 patients with Wilson disease, they found 20 new mutations as well as 3 of the 5 previously published mutations: 11 small insertions and deletions, 7 missense mutations, 2 nonsense mutations, and 3 splice site mutations. Two of the mutations, his1070 to gly (<a href="#0006">606882.0006</a>) and gly1267 to arg (<a href="#0007">606882.0007</a>), are relatively frequent, together accounting for 38% of mutations in patients of European origin. Their findings suggested a wide span in the age of onset of Wilson disease, perhaps wider than previously considered typical. Mutations that completely disrupt the gene can produce liver disease in early childhood at a time when Wilson disease may not be considered in the differential diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" 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>Given the difficulties of searching for mutations in a gene spanning more than 80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. <a href="#42" class="mim-tip-reference" title="Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>Haplotypes and mutations in Wilson disease.</strong> Am. J. Hum. Genet. 56: 1315-1319, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762553</a>]" pmid="7762553">Thomas et al. (1995)</a> did haplotyping of the Wilson disease gene region in 58 families. These haplotypes, combining 3 markers (D13S314, D13S316, and D13S301), were usually specific for each different mutation. The haplotype data suggested that as many as 20 mutations might still be unidentified; a total of 25 disease-causing mutations had been identified at that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. <strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong> Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>]" pmid="8533760">Figus et al. (1995)</a> identified 16 novel mutations in 127 affected patients of Mediterranean descent: 8 frameshifts, 7 missense mutations, and 1 splicing defect. In addition, they detected 5 previously described mutations, e.g., his1070-to-gln (<a href="#0006">606882.0006</a>), which accounted for 13% of the mutations in WND chromosomes in non-Sardinian Mediterranean populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533760" 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="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A. <strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong> Hum. Mutat. 14: 294-303, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502776</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<294::AID-HUMU4>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502776">Loudianos et al. (1999)</a> characterized the putative promoter and 5-prime untranslated region of the WD gene and carried out mutation analysis in this region in Sardinian WD patients with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion (<a href="#0010">606882.0010</a>) in all chromosomes with this common haplotype. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M. <strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong> Hum. Mutat. 12: 89-94, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9671269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9671269</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:2<89::AID-HUMU3>3.0.CO;2-G" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9671269">Loudianos et al. (1998)</a> performed a mutation screen on the WND gene in 59 patients of Mediterranean origin: 26 Continental Italians, 22 Sardinians, 9 Turkish, and 2 Albanians. They found 31 novel and 3 known mutations. Most of the patients were compound heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9671269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H. <strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong> Hum. Mutat. 11: 275-278, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554743</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<275::AID-HUMU4>3.0.CO;2-L" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554743">Kim et al. (1998)</a> identified 3 novel mutations in the ATP7B gene in Korean patients with Wilson disease. One of these, arg778 to leu (R778L; <a href="#0009">606882.0009</a>), was found in 6 of 8 unrelated patients, giving an allele frequency of 37.5%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Duc, H.-H., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G. <strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong> Europ. J. Hum. Genet. 6: 616-623, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887381</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887381">Duc et al. (1998)</a> performed mutation analysis in 33 German and 10 Cuban unrelated Wilson disease patients. The common his1069-to-gln (<a href="#0006">606882.0006</a>) mutation accounted for 42% of all WND chromosomes in the German series and haplotype C was found to be highly predictive for this mutation. Six previously undescribed WND gene mutations were identified. In 15 German WND index patients and 3 sibs, both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the his1069-to-gln mutation showed almost a complete range of clinical presentations; thus, in this study, the his1069-to-gln mutation was not associated with a late neurologic presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H. <strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.</strong> Hum. Mutat. 15: 454-462, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790207</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<454::AID-HUMU7>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790207">Okada et al. (2000)</a> analyzed the ATP7B gene in 41 unrelated Japanese Wilson disease families, including 47 patients. They identified 21 mutations, 9 of which were novel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 84 Chinese patients with Wilson disease from 65 unrelated families, <a href="#47" class="mim-tip-reference" title="Wu, Z.-Y., Wang, N., Lin, M.-T., Fang, L., Murong, S.-X., Yu, L. <strong>Mutation analysis and the correlation between genotype and phenotype of arg778leu mutation in Chinese patients with Wilson disease.</strong> Arch. Neurol. 58: 971-976, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11405812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11405812</a>] [<a href="https://doi.org/10.1001/archneur.58.6.971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11405812">Wu et al. (2001)</a> identified 18 mutations (7 novel) and 11 polymorphisms (3 novel) in the ATB7B gene. The most common mutations were R778L and T935M, which were present at a frequency of 37.7% and 10.0%, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11405812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Loudianos, G., Lovicu, M., Dessi, V., Tzetis, M., Kanavakis, E., Zancan, L., Zelante, L., Galvez-Galvez, C., Cao, A. <strong>Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B.</strong> Hum. Mutat. 20: 260-266, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12325021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12325021</a>] [<a href="https://doi.org/10.1002/humu.10121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12325021">Loudianos et al. (2002)</a> stated that more than 200 Wilson disease-causing mutations had been defined, most of which were missense mutations, while splice site mutations were limited in number. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12325021" 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="#49" class="mim-tip-reference" title="Yoo, H. W. <strong>Identification of novel mutations and the 3 most common mutations in the human ATP7B gene of Korean patients with Wilson disease.</strong> Genet. Med. 4: 43S-48S, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12544487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12544487</a>] [<a href="https://doi.org/10.1097/00125817-200211001-00009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12544487">Yoo (2002)</a> studied 37 patients from 33 unrelated Korean families with Wilson disease and identified 12 different mutations, of which 6 were novel. The R778L mutation, which is known to be highly prevalent in Asian patients, was found with a frequency of 37.9% among the Korean population, which is significantly higher than that among the Japanese and Taiwanese. The N1270S mutation (<a href="/entry/606682#0017">606682.0017</a>), which is presumed to disrupt the ATP hinge domain of the ATP7B protein, was the next most common mutation in Korean patients, with an allele frequency of 12.1%. The A874V mutation (<a href="/entry/606682#0016">606682.0016</a>) was the third most common, accounting for 9.4%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12544487" 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="#28" class="mim-tip-reference" title="Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E. <strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong> Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523622</a>] [<a href="https://doi.org/10.1002/ajmg.a.30345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523622">Panagiotakaki et al. (2004)</a> analyzed the results of molecular analysis on a cohort that included 93 index patients with Wilson disease from 69 unrelated families in Greece. Detailed phenotypic evaluation was added to the findings reported previously by Loudianos et al. (<a href="#22" class="mim-tip-reference" title="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M. <strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong> Hum. Mutat. 12: 89-94, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9671269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9671269</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:2<89::AID-HUMU3>3.0.CO;2-G" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9671269">1998</a>, <a href="#24" class="mim-tip-reference" title="Loudianos, G., Lovicu, M., Solinas, P., Kanavakis, E., Tzetis, M., Manolaki, N., Panagiotakaki, E., Karpathios, T., Cao, A. <strong>Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.</strong> Genet. Test. 4: 399-402, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11216666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11216666</a>] [<a href="https://doi.org/10.1089/109065700750065162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11216666">2000</a>). Twenty different mutations accounted for 86% of the WND chromosomes. The 2 most common mutations were H1069Q (<a href="#0006">606882.0006</a>), found in 35% of WND chromosomes, and R969Q (<a href="#0018">606882.0018</a>), found in 12%. Homozygosity for H1069Q was found in 13 patients and for R969Q in 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9671269+15523622+11216666" 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="#26" class="mim-tip-reference" title="Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F. <strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong> Clin. Genet. 68: 61-68, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952988</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00439.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15952988">Margarit et al. (2005)</a> analyzed 40 unrelated Spanish patients with Wilson disease and identified 21 different mutations in the ATP7B gene in 35 (87%) patients. The M645R (<a href="#0020">606882.0020</a>) mutation was particularly prevalent and was found in 22 patients (55%), who were all compound heterozygotes for mutation in the ATP7B gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Dedoussis, G. V. Z., Genschel, J., Sialvera, T.-E., Bochow, B., Manolaki, N., Manios, Y., Tsafantakis, E., Schmidt, H. <strong>Wilson disease: high prevalence in a mountaineous (sic) area of Crete.</strong> Ann. Hum. Genet. 69: 268-274, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15845031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15845031</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2005.00171.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15845031">Dedoussis et al. (2005)</a> observed an increased number of WD patients on the island of Crete and studied the spectrum of mutations in a small village close to the city of Heraklion. Of 90 births in the village since 1978, 6 were found to have WD. Analysis of the entire gene in 3 WD patients and in relatives of a boy who died from WD led to the detection of 4 different mutations. Two missense mutations (see <a href="#0021">606882.0021</a>) cosegregated in cis in the same patient. The other allele of this patient carried a nonsense mutation (<a href="#0022">606882.0022</a>). This was said to have been the first report of 3 mutations cosegregating in the same WD patient. The fourth mutation identified was a novel frameshift mutation with documented cosegregation with WD. A screen of 200 inhabitants originating from the same area demonstrated that 18 were carriers of one of these mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15845031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K. <strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong> Hum. Genet. 118: 49-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133174</a>] [<a href="https://doi.org/10.1007/s00439-005-0007-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16133174">Gupta et al. (2005)</a> analyzed Indian patients with Wilson disease from 62 unrelated families and their first-degree relatives and identified a total of 9 mutations, 5 novel, in the ATP7B gene. The authors noted that homozygotes for different mutations that would be expected to produce similar defective proteins showed significant disparity in terms of organ involvement and severity of disease; in 1 family, 2 sibs with the same pair of mutant chromosomes had remarkably different phenotypes. <a href="#14" class="mim-tip-reference" title="Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K. <strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong> Hum. Genet. 118: 49-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133174</a>] [<a href="https://doi.org/10.1007/s00439-005-0007-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16133174">Gupta et al. (2005)</a> suggested that there may be as yet unidentified modifying loci that account for the observed phenotypic heterogeneity among patients with Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16133174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 120 unrelated Korean patients with Wilson disease, <a href="#30" class="mim-tip-reference" title="Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W. <strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong> Hum. Mutat. 28: 1108-1113, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17587212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17587212</a>] [<a href="https://doi.org/10.1002/humu.20574" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17587212">Park et al. (2007)</a> identified 28 different mutations, including 6 novel mutations, in the ATP7B gene. R778L was the most common mutation, occurring in 39.2% of mutant alleles. Functional studies of some of the mutant proteins in yeast cells and COS-7 cells showed impaired copper transport and aberrant cellular localization of mutant ATP7B proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17587212" 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="#44" class="mim-tip-reference" title="Wallace, D. F., Dooley, J. S. <strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong> Hum. Genet. 139: 1065-1075, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32248359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32248359</a>] [<a href="https://doi.org/10.1007/s00439-020-02161-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32248359">Wallace and Dooley (2020)</a> found that of the 732 Wilson disease-associated ATP7B mutations reported by 2017, most (55%) were missense mutations. Of the 732 mutations, 231 were present in the gnomAD database, giving an initial estimated population prevalence of 1 in 2,400. <a href="#44" class="mim-tip-reference" title="Wallace, D. F., Dooley, J. S. <strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong> Hum. Genet. 139: 1065-1075, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32248359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32248359</a>] [<a href="https://doi.org/10.1007/s00439-020-02161-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32248359">Wallace and Dooley (2020)</a> assessed the penetrance/pathogenicity of ATP7B mutations by comparing gnomAD allele frequencies with the number of reports of each mutation and then using a variant effect prediction algorithm. When the authors reassessed the pathogenic allele frequency of ATP7B mutations excluding those likely to have low penetrance, they calculated the population prevalence of Wilson disease to be 1 in 20,000 individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32248359" 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="#28" class="mim-tip-reference" title="Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E. <strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong> Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523622</a>] [<a href="https://doi.org/10.1002/ajmg.a.30345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523622">Panagiotakaki et al. (2004)</a> studied a Wilson disease cohort that included 93 Greek index patients from 69 unrelated families and reported that the H1069Q and R969Q mutations appeared to confer a milder disease as patients showed disease onset at a later age and also were associated with milder severity when found in trans (compound heterozygosity) with severe mutations. Predicted nonsense and frameshift mutations were associated with severe phenotypic expression with earlier disease onset and lower ceruloplasmin values. <a href="#28" class="mim-tip-reference" title="Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E. <strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong> Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523622</a>] [<a href="https://doi.org/10.1002/ajmg.a.30345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523622">Panagiotakaki et al. (2004)</a> noted that their findings on the phenotypic effect of predicted nonsense and frameshift mutations were especially important for early medical intervention in presymptomatic infants and children with these genotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A. <strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.</strong> Clin. Genet. 68: 524-532, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16283883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16283883</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00528.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16283883">Gromadzka et al. (2005)</a> studied 142 Polish patients with Wilson disease and identified 26 mutations in the ATP7B gene: 11 truncating, 14 missense, and 1 splice site mutation. Patients with 1 or 2 truncating mutations had lower serum copper and ceruloplasmin levels and were younger when the first symptoms of the disease appeared compared with individuals with 2 missense mutations, and the effect of truncating mutations on phenotype was dose-dependent. <a href="#12" class="mim-tip-reference" title="Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A. <strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.</strong> Clin. Genet. 68: 524-532, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16283883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16283883</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00528.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16283883">Gromadzka et al. (2005)</a> found no association between type of ATP7B mutation and mode of initial disease presentation (neurologic, hepatic, or mixed). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16283883" 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="#39" class="mim-tip-reference" title="Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T. <strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong> J. Biol. Chem. 273: 1815-1820, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430732</a>] [<a href="https://doi.org/10.1074/jbc.273.3.1815" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430732">Terada et al. (1998)</a> introduced human ATP7B cDNA into the LEC rat using recombinant adenovirus-mediated gene delivery. An immunofluorescence study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LEC rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of ATP7B protein with respect to copper transport. Holoceruloplasmin was found in plasma of LEC rats who received ATP7B cDNA. <a href="#39" class="mim-tip-reference" title="Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T. <strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong> J. Biol. Chem. 273: 1815-1820, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430732</a>] [<a href="https://doi.org/10.1074/jbc.273.3.1815" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430732">Terada et al. (1998)</a> concluded that introduced ATP7B protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for ATP7B protein to manifest its function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430732" 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=606882[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"><span class="text-primary">●</span> rs779904655 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs779904655;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/rs779904655?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=rs779904655" 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=rs779904655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>To confirm the conclusion that the gene they identified in a YAC from the 13q14.3 region and referred to as Wc1 was indeed the gene mutated in Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a> studied 30 patients with the disorder selected to represent 29 different haplotypes based on 3 close markers. Using 3 cDNA fragments and 3 restriction enzymes, they found no altered fragments or dosage differences indicative of gross deletions. Single-strand conformation polymorphism analysis and heteroduplex analysis were performed in 27 patients. Both methods revealed a particular band shift, which on sequencing was found to represent homozygosity for the same 7-bp deletion, removing bases 1950-1956 of their sequence, causing a frameshift that resulted in an immediate stop codon at position 639 in the amino acid sequence, and removing the entire C-terminal half of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The name of the 7-bp deletion (1950del7), originally described by <a href="#2" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. <strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong> Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>] [<a href="https://doi.org/10.1038/ng1293-327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298639">Bull et al. (1993)</a>, was changed to 2010del7 to be consistent with the position of the ATG start codon identified by <a href="#33" class="mim-tip-reference" title="Petrukhin, K. E., Lutsenko, S., Chernov, I., Ross, B. M., Kaplan, J. H., Gilliam, T. C. <strong>Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions.</strong> Hum. Molec. Genet. 3: 1647-1656, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7833924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7833924</a>] [<a href="https://doi.org/10.1093/hmg/3.9.1647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7833924">Petrukhin et al. (1994)</a>. The same mutation was found by <a href="#41" class="mim-tip-reference" title="Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W. <strong>Wilson disease in Iceland: a clinical and genetic study.</strong> Am. J. Hum. Genet. 56: 1140-1146, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726170</a>]" pmid="7726170">Thomas et al. (1995)</a> in affected members of 2 large kindreds in Iceland. Haplotype data and the nature of the mutation supported the existence of a founder chromosome. Although the protein function was predicted to be completely abolished by the deletion, predicting early-onset liver disease, <a href="#41" class="mim-tip-reference" title="Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W. <strong>Wilson disease in Iceland: a clinical and genetic study.</strong> Am. J. Hum. Genet. 56: 1140-1146, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726170</a>]" pmid="7726170">Thomas et al. (1995)</a> found that the patients presented with later-onset neurologic and psychiatric symptoms. They showed that alternative splicing of the transcript in the region of the deletion may have contributed to later onset, suggesting that alternative isoforms of the protein may have functional significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7833924+7726170+8298639" 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> rs76151636 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs76151636;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/rs76151636?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=rs76151636" 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=rs76151636" 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=RCV000004052 OR RCV000078049 OR RCV002321470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004052, RCV000078049, RCV002321470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004052...</a>
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<p>In 31% of Wilson disease (WND; <a href="/entry/277900">277900</a>) chromosomes in 50 unrelated Americans and in 22% of Wilson disease chromosomes in 18 unrelated Russian families, <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> found a C-to-A transversion at nucleotide 2142 in the ATP7B gene, causing a substitution of glutamine for histidine-714 in the phosphorylation domain of the protein. <a href="#16" class="mim-tip-reference" title="Houwen, R. H. J., Juyn, J., Hoogenraad, T. U., Ploos van Amstel, J. K., Berger, R. <strong>H714Q mutation in Wilson disease is associated with late, neurological presentation.</strong> J. Med. Genet. 32: 480-482, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7666402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7666402</a>] [<a href="https://doi.org/10.1136/jmg.32.6.480" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7666402">Houwen et al. (1995)</a> analyzed 38 Dutch symptomatic Wilson disease patients for the H714Q mutation. Ten patients homozygous for the mutation presented at a mean age of 20.3 (SD 6.1) years, with either neurologic symptoms or a Kayser-Fleischer ring. Six patients with the H714Q mutation in one chromosome and an unknown mutation in the other chromosome presented at a mean age of 17.8 (SD 5.8) years, with either neurologic or hepatic symptoms. With the exception of 1, all 22 patients with an uncharacterized mutation in both chromosomes presented with liver involvement at a mean age of 9.9 (SD 2.4) years. The findings suggest that the H714Q mutation is a relatively mild one, possibly with some residual function in the copper transporting protein, resulting in a slower build-up of copper. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7666402+8298641" 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>.0003 WILSON DISEASE</strong>
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ATP7B, ASN915SER
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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> rs121907990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907990;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/rs121907990?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=rs121907990" 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=rs121907990" 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=RCV000004063 OR RCV000196058 OR RCV000504595 OR RCV000595271 OR RCV002354147 OR RCV003904803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004063, RCV000196058, RCV000504595, RCV000595271, RCV002354147, RCV003904803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004063...</a>
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<p>In a Sicilian case of Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> found an A-to-G transition at nucleotide 2744, resulting in substitution of serine for asparagine-915 in the hinge region of the ATP-binding site. This region is highly conserved in all P-type ATPases. The Sicilian patient was homozygous for the mutation and was also homozygous for a 6-marker haplotype that had not been observed in other individuals in their sample of 115 Wilson disease families. Thus, it appears to be a rare mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 WILSON DISEASE</strong>
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ATP7B, 1-BP DEL, 2337C
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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> rs137853281 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853281;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/rs137853281?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=rs137853281" 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=rs137853281" 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=RCV000169026 OR RCV000523051 OR RCV004965273" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169026, RCV000523051, RCV004965273" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169026...</a>
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<p>In 2 Russian patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> found homozygosity for a single basepair deletion, a cytosine at position 2337. This resulted in a frameshift at amino acid 779. In both families, the parents were heterozygous for the mutation, as was a single unaffected sib. The mutation accounted for approximately 20% of Wilson disease chromosomes in a sample of 18 unrelated Russian families. It was found once in an American sample of 50 unrelated families. It was predicted that the mutation would truncate the Wilson disease protein within the phosphorylation region, thereby disabling its function in persons homozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" 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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ATP7B, 1-BP INS, NT2487
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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> rs748924063 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs748924063;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/rs748924063?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=rs748924063" 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=rs748924063" 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=RCV000169520" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169520" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169520</a>
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<p>On 1 chromosome of an American patient with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#38" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. <strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong> Nature Genet. 5: 344-350, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>] [<a href="https://doi.org/10.1038/ng1293-344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8298641">Tanzi et al. (1993)</a> found insertion of an extra thymine residue after thymine 2487, resulting in a frameshift at amino acid 829. The change in the protein was in the amphiphilic helix between the phosphorylation and ATP-binding domains. The second disease allele in this patient had not been identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" 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> rs76151636 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs76151636;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/rs76151636?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=rs76151636" 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=rs76151636" 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=RCV000004052 OR RCV000078049 OR RCV002321470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004052, RCV000078049, RCV002321470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004052...</a>
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<p>In a study of 58 patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> found that 28% had a mutation that they referred to as H1070Q (HIS1070GLN), located in the loop motif and disrupting ATP binding. The patients (19 in number) were of Eastern European, German, French, and British extraction. This mutation was homozygous in 6 families; there was variation in age of onset within these families and an equal number of hepatic and neurologic cases. The average age of onset of symptoms in patients homozygous for the mutation was 16.8 years. The same mutation was found in heterozygous state (compound heterozygotes) in 9 families with a total of 11 patients, with an average age of onset of 17.3 years. <a href="#7" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. <strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong> Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>]" pmid="8533760">Figus et al. (1995)</a> concluded that this mutation is probably the most common molecular defect of the WND gene and may have arisen as a single and very ancient mutation event. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8533760+7626145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Payne, A. S., Kelly, E. J., Gitlin, J. D. <strong>Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation.</strong> Proc. Nat. Acad. Sci. 95: 10854-10859, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9724794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9724794</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9724794[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.18.10854" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9724794">Payne et al. (1998)</a> stated that the H1069Q mutation represents up to 37% of Wilson disease alleles in patients of Eastern European descent and studied the function of the ATP7B protein by expressing wildtype and mutant ATP7B cDNAs in a Menkes copper transporter-deficient 'mottled' fibroblast cell line defective in copper export. Expression of the wildtype cDNA demonstrated trans-Golgi network localization and copper-dependent trafficking of the ATP7B protein identical to previous observations for the endogenously expressed protein in hepatocytes. Furthermore, expression of the ATP7B cDNA rescued the 'mottled' phenotype as evidenced by a reduction in copper accumulation and restoration of cell liability. In contrast, expression of an H1069Q mutant ATP7B cDNA did not rescue the 'mottled' phenotype, and immunofluorescence studies showed that this mutant ATP7B protein was localized in the endoplasmic reticulum. Pulse-chase analysis demonstrated a 5-fold decrease in the half-life of the H1069Q mutant as compared with the wildtype protein. Maintenance of these transfected cell lines at 28 degrees C resulted in localization of the H1069Q protein in the trans-Golgi network, suggesting that a temperature-sensitive defect in protein folding followed by degradation constitutes the molecular basis of Wilson disease in patients harboring the H1069Q mutation. The results provided compelling evidence that the ATP7B protein can functionally substitute for the Menkes disease protein, ATP7A, supporting the concept that these proteins use common biochemical mechanisms to effect cellular copper homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9724794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Duc, H.-H., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G. <strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong> Europ. J. Hum. Genet. 6: 616-623, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887381</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887381">Duc et al. (1998)</a> found this mutation in 42% of WND chromosomes in a series of 33 German cases of Wilson disease. Haplotype C was highly predictive for this mutation. Patients homozygous for the mutation showed almost a complete range of clinical presentations; in this series, the his1069-to-gln mutation was not associated with a late neurologic presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Firneisz, G., Lakatos, P. L., Szalay, F., Polli, C., Glant, T. T., Ferenci, P. <strong>Common mutations of ATP7B in Wilson disease patients from Hungary.</strong> Am. J. Med. Genet. 108: 23-28, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857545</a>] [<a href="https://doi.org/10.1002/ajmg.10220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11857545">Firneisz et al. (2002)</a> found the H1069Q mutation in 27 Hungarian patients with Wilson disease, 64.3% of their series. In 9 of the 27 patients, H1069Q was homozygous. They found that H1069Q-positive patients from various European countries had the same haplotype pattern. Thus the H1069Q mutation appears to have originated from a single founder, at least in Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857545" 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 80 unrelated Bulgarian families with Wilson disease, <a href="#43" class="mim-tip-reference" title="Todorov, T., Savov, A., Jelev, H., Panteleeva, E., Konstantinova, D., Krustev, Z., Mihaylova, V., Tournev, I., Tankova, L., Tzolova, N., Kremensky, I. <strong>Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. (Letter)</strong> Clin. Genet. 68: 474-476, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16207219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16207219</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00516.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16207219">Todorov et al. (2005)</a> found that the H1069Q mutation was the most common mutation with an allelic frequency of 58.75%. All 15 families of the Roma ethnic group had the H1069Q mutation, consistent with the Roma being a genetic isolate with frequent consanguinity and endogamy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16207219" 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> rs121907992 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907992;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/rs121907992?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=rs121907992" 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=rs121907992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a series of 58 patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> found that 7 (10%), of French and British extraction, had a gly1267-to-arg mutation. Located in the ATP hinge domain, the mutation disrupted the hinge. (The article by <a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> listed this mutation as GLY1267LYS; a published correction provided the proper amino acid substitution.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a series of 58 patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> found 4 with mutations predicted to destroy the function of the gene (insertion, deletion, nonsense, or frameshift). The average age of onset in these cases was 7 years. Most striking was the age of onset of a patient homozygous for a G-to-C transversion at nucleotide 1711. The patient, of American Indian extraction, presented with liver disease at 3 years of age. The mutation at the acceptor splice site of intron 4 resulted in the deletion of exon 5 and the removal of 54 amino acids, including the last copper-binding domain, from the protein product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" 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="#46" class="mim-tip-reference" title="Wilson, D. C., Phillips, M. J., Cox, D. W., Roberts, E. A. <strong>Severe hepatic Wilson's disease in preschool-aged children.</strong> J. Pediat. 137: 719-722, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11060541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11060541</a>] [<a href="https://doi.org/10.1067/mpd.2000.108569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11060541">Wilson et al. (2000)</a> reported a 3-year-old Indo-Pakistani girl, born to consanguineous parents, who was diagnosed with Wilson disease after presenting with hemolytic anemia, hepatosplenomegaly, ascites, and evidence of decompensated chronic liver disease. DNA analysis revealed that she was homozygous for the IVS4-1G-C mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11060541" 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> rs28942074 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28942074;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/rs28942074?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=rs28942074" 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=rs28942074" 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=RCV000004056 OR RCV000389880 OR RCV002444420 OR RCV003398441" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004056, RCV000389880, RCV002444420, RCV003398441" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004056...</a>
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<p><a href="#17" class="mim-tip-reference" title="Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H. <strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong> Hum. Mutat. 11: 275-278, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554743</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<275::AID-HUMU4>3.0.CO;2-L" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554743">Kim et al. (1998)</a> found a CGG-to-CTG transversion in exon 8 of the ATP7B gene, leading to an arg778-to-leu (R778L) amino acid substitution in 6 of 8 unrelated Korean patients with Wilson disease (WND; <a href="/entry/277900">277900</a>). They cited the allele frequency as 37.5% and quoted previous findings indicating a considerable frequency of this allele in Japanese (27.7%), Taiwanese (27%), and Chinese (11.1%) Wilson disease patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kusuda, Y., Hamaguchi, K., Mori, T., Shin, R., Seike, M., Sakata, T. <strong>Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.</strong> J. Hum. Genet. 45: 86-91, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10721669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10721669</a>] [<a href="https://doi.org/10.1007/s100380050017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10721669">Kusuda et al. (2000)</a> described the R788L mutation in compound heterozygous state with an in-frame deletion, 3892delGTC (<a href="#0011">606882.0011</a>), in a Japanese patient. Likewise, they commented on the high frequency of this mutation in Asians and stated that it has not been reported in Caucasian patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10721669" 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="#47" class="mim-tip-reference" title="Wu, Z.-Y., Wang, N., Lin, M.-T., Fang, L., Murong, S.-X., Yu, L. <strong>Mutation analysis and the correlation between genotype and phenotype of arg778leu mutation in Chinese patients with Wilson disease.</strong> Arch. Neurol. 58: 971-976, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11405812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11405812</a>] [<a href="https://doi.org/10.1001/archneur.58.6.971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11405812">Wu et al. (2001)</a> reported the frequency of the R788L mutation in Chinese patients to be 37.7%, which represented the most common mutation found in 84 patients with Wilson disease. The authors also found that homozygosity for the mutation was associated with a significantly earlier age of disease onset, lower levels of ceruloplasmin, and hepatic symptoms at presentation as compared to heterozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11405812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Gu, Y.-H., Kodama, H., Du, S.-L., Gu, Q.-J., Sun, H.-J., Ushijima, H. <strong>Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.</strong> Clin. Genet. 64: 479-484, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14986826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14986826</a>] [<a href="https://doi.org/10.1046/j.1399-0004.2003.00179.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14986826">Gu et al. (2003)</a> likewise found the R778L mutation in 55% of Chinese Han and Hui patients in at least 1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14986826" 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="#30" class="mim-tip-reference" title="Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W. <strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong> Hum. Mutat. 28: 1108-1113, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17587212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17587212</a>] [<a href="https://doi.org/10.1002/humu.20574" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17587212">Park et al. (2007)</a> found that the R778L mutation had an allele frequency of 39.2% among 120 unrelated Korean patients with Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17587212" 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="#29" class="mim-tip-reference" title="Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W. <strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong> Clin. Genet. 75: 405-407, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19419418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19419418</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01132.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19419418">Park et al. (2009)</a> found heterozygosity for the R778L allele in 6 of 500 healthy Korean individuals, yielding a carrier frequency of 0.6% in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" 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="#45" class="mim-tip-reference" title="Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M. <strong>Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.</strong> J. Hum. Genet. 56: 660-665, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21796144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21796144</a>] [<a href="https://doi.org/10.1038/jhg.2011.76" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21796144">Wang et al. (2011)</a> found that the R778L mutation was the most common mutation among 69 Chinese patients with Wilson disease, accounting for 23.29% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21796144" 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">rs1484840087 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1484840087;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=rs1484840087" 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=rs1484840087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#21" class="mim-tip-reference" title="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A. <strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong> Hum. Mutat. 14: 294-303, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502776</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<294::AID-HUMU4>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502776">Loudianos et al. (1999)</a> characterized the putative promoter and 5-prime untranslated region of the WND gene and carried out mutation analysis in this region in Sardinian patients with Wilson disease (WND; <a href="/entry/277900">277900</a>) with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion from position -441 to position -427, 5-prime to the translation start site within the 5-prime UTR in all chromosomes with this common haplotype. Expression assays demonstrated a 75% reduction in the transcriptional activity of the mutated sequence compared to that of the normal sequence. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502776" 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="Cullen, L. M., Prat, L., Cox, D. W. <strong>Genetic variation in the promoter and 5-prime UTR of the copper transporter, ATP7B, in patients with Wilson disease.</strong> Clin. Genet. 64: 429-432, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14616767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14616767</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00160.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14616767">Cullen et al. (2003)</a> examined genetic variation in the promoter and 5-prime UTR of the ATP7B gene in patients with Wilson disease. Three of 37 patients were heterozygous for the 15-bp deletion between nucleotides -424 and -441. In addition, 2 novel single-nucleotide changes were identified within the 5-prime UTR and promoter of ATP7B, but these were found at a similar frequency in control chromosomes and were apparently normal variants. The results suggested that mutations in regulatory elements of ATP7B are uncommon in patients of European ancestry, except in Sardinia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14616767" 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">rs2138570625 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2138570625;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=rs2138570625" 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=rs2138570625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Japanese patient with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#18" class="mim-tip-reference" title="Kusuda, Y., Hamaguchi, K., Mori, T., Shin, R., Seike, M., Sakata, T. <strong>Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.</strong> J. Hum. Genet. 45: 86-91, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10721669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10721669</a>] [<a href="https://doi.org/10.1007/s100380050017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10721669">Kusuda et al. (2000)</a> found compound heterozygosity for an in-frame GTC deletion (3892delGTC), predicted to remove a valine residue, and the frequent Asian mutation R778L (<a href="#0009">606882.0009</a>), which apparently has not been observed in Caucasians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10721669" 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> rs28942075 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28942075;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/rs28942075?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=rs28942075" 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=rs28942075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#7" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. <strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong> Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>]" pmid="8533760">Figus et al. (1995)</a> identified a GAC-to-AAC change in the ATP7B gene, resulting in an asp765-to-asn substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533760" 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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ATP7B, GLY943SER
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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> rs28942076 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28942076;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/rs28942076?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=rs28942076" 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=rs28942076" 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=RCV000004060 OR RCV001091638" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004060, RCV001091638" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004060...</a>
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<p>In patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> identified a GGT-to-AGT change in the ATP7B gene, resulting in a gly943-to-ser mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0014" class="mim-anchor"></a>
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<strong>.0014 WILSON DISEASE</strong>
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ATP7B, ARG919GLY
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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> rs121907993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907993;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/rs121907993?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=rs121907993" 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=rs121907993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004061 OR RCV001818123 OR RCV004678595" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004061, RCV001818123, RCV004678595" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004061...</a>
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<p>In 3 sibs with disparate clinical phenotypes of Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#37" class="mim-tip-reference" title="Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T. <strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong> J. Hum. Genet. 47: 543-547, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376745</a>] [<a href="https://doi.org/10.1007/s100380200082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376745">Takeshita et al. (2002)</a> found compound heterozygosity for 2 ATP7B mutations: R778L (<a href="#0009">606882.0009</a>) and R919G. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0015" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0015 WILSON DISEASE</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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ATP7B, 1-BP DEL, 2511A
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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> rs777362050 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs777362050;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/rs777362050?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=rs777362050" 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=rs777362050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000169035" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169035" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169035</a>
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<span class="mim-text-font">
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<p>In a family in which 2 sibs had disparate Wilson disease (WND; <a href="/entry/277900">277900</a>) phenotypes, <a href="#37" class="mim-tip-reference" title="Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T. <strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong> J. Hum. Genet. 47: 543-547, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376745</a>] [<a href="https://doi.org/10.1007/s100380200082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376745">Takeshita et al. (2002)</a> found that each had compound heterozygosity for 2 ATP7B mutations: 2511delA and A874V (<a href="#0016">606882.0016</a>). In this family, the second male child showed neurologic symptoms at 32 years of age and was found to have the hepatoneurologic type of Wilson disease; on subsequent family screening, the 35-year-old first female sib was found to have the hepatic form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" 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="0016" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0016 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, ALA874VAL
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</div>
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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> rs121907994 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907994;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/rs121907994?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=rs121907994" 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=rs121907994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004055 OR RCV001091639" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004055, RCV001091639" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004055...</a>
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</span>
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<span class="mim-text-font">
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<p>For discussion of the ala874-to-val (A874V) mutation in the ATP7B gene that was found in compound heterozygous state in 2 sibs with Wilson disease (WND; <a href="/entry/277900">277900</a>) by <a href="#37" class="mim-tip-reference" title="Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T. <strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong> J. Hum. Genet. 47: 543-547, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376745</a>] [<a href="https://doi.org/10.1007/s100380200082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376745">Takeshita et al. (2002)</a>, see <a href="#0015">606882.0015</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" 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="#29" class="mim-tip-reference" title="Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W. <strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong> Clin. Genet. 75: 405-407, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19419418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19419418</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01132.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19419418">Park et al. (2009)</a> found heterozygosity for the A874V allele in 2 of 500 healthy Korean individuals, yielding a carrier frequency of 0.2% in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" 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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</span>
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<div>
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<a id="0017" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0017 WILSON DISEASE</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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ATP7B, ASN1270SER
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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> rs121907990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907990;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/rs121907990?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=rs121907990" 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=rs121907990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004063 OR RCV000196058 OR RCV000504595 OR RCV000595271 OR RCV002354147 OR RCV003904803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004063, RCV000196058, RCV000504595, RCV000595271, RCV002354147, RCV003904803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004063...</a>
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<div>
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<span class="mim-text-font">
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<p><a href="#40" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. <strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong> Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>] [<a href="https://doi.org/10.1038/ng0295-210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626145">Thomas et al. (1995)</a> identified an asn1270-to-ser (N1270S) mutation, which they referred to as asn1271-to-ser (N1271S), in the ATP7B gene in an Italian patient with Wilson disease (WND; <a href="/entry/277900">277900</a>). This mutation was found to account for 61% of all mutations in Costa Rican patients and 4.9% in Japanese patients (<a href="#27" class="mim-tip-reference" title="Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H. <strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.</strong> Hum. Mutat. 15: 454-462, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790207</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<454::AID-HUMU7>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790207">Okada et al., 2000</a>; <a href="#36" class="mim-tip-reference" title="Shah, A. B., Chernov, I., Zhang, H. T., Ross, B. M., Das, K., Lutsenko, S., Parano, E., Pavone, L., Evgrafov, O., Ivanova-Smolenskaya, I. A., Anneren, G., Westermark, K., Urrutia, F. H., Penchaszadeh, G. K., Sternlieb, I., Scheinberg, I. H., Gilliam, T. C., Petrukhin, K. <strong>Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation and functional analyses.</strong> Am. J. Hum. Genet. 61: 317-328, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311736</a>] [<a href="https://doi.org/10.1086/514864" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311736">Shah et al., 1997</a>). <a href="#49" class="mim-tip-reference" title="Yoo, H. W. <strong>Identification of novel mutations and the 3 most common mutations in the human ATP7B gene of Korean patients with Wilson disease.</strong> Genet. Med. 4: 43S-48S, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12544487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12544487</a>] [<a href="https://doi.org/10.1097/00125817-200211001-00009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12544487">Yoo (2002)</a> found this mutation in 12.1% of Korean patients with Wilson disease. In most cases it was found in compound heterozygosity with the R778L mutation (<a href="#0009">606882.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9311736+12544487+10790207+7626145" 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="#29" class="mim-tip-reference" title="Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W. <strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong> Clin. Genet. 75: 405-407, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19419418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19419418</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01132.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19419418">Park et al. (2009)</a> found heterozygosity for the N1270S allele in 2 of 500 healthy Korean individuals, yielding a carrier frequency of 0.2% in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0018 WILSON DISEASE</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> rs121907996 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907996;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/rs121907996?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=rs121907996" 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=rs121907996" 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=RCV000004064 OR RCV000270891 OR RCV003904804" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004064, RCV000270891, RCV003904804" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004064...</a>
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<p>In patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#7" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. <strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong> Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>]" pmid="8533760">Figus et al. (1995)</a> identified a 2906G-A transition in exon 13 of the ATP7B gene, resulting in an arg969-to-gln (R969Q) substitution. <a href="#28" class="mim-tip-reference" title="Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E. <strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong> Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523622</a>] [<a href="https://doi.org/10.1002/ajmg.a.30345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523622">Panagiotakaki et al. (2004)</a> found this mutation in 12% of chromosomes from 93 Greek patients with Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15523622+8533760" 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> rs121907997 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907997;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/rs121907997?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=rs121907997" 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=rs121907997" 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=RCV000004065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004065</a>
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<p>In a patient with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#32" class="mim-tip-reference" title="Pendlebury, S. T., Rothwell, P. M., Dalton, A., Burton, E. A. <strong>Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation.</strong> Neurology 63: 1982-1983, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557537</a>] [<a href="https://doi.org/10.1212/01.wnl.0000144192.30426.38" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557537">Pendlebury et al. (2004)</a> identified a homozygous thr766-to-arg (T766R) substitution in the ATP7B gene within transmembrane domain 4 of the protein. The case was unusual in that the patient presented with sudden onset of slurred speech, dysphagia, and difficulty walking. A preliminary diagnosis of ischemic stroke was made, but a more detailed work-up suggested Wilson disease. Both parents were heterozygous for the mutation and originated from the same small village in central England. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557537" 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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ATP7B, MET645ARG
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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> rs121907998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907998;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/rs121907998?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=rs121907998" 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=rs121907998" 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=RCV000004066 OR RCV001508347 OR RCV002408449 OR RCV003398442" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004066, RCV001508347, RCV002408449, RCV003398442" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004066...</a>
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<p>In 22 of 40 (55%) unrelated Spanish patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#26" class="mim-tip-reference" title="Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F. <strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong> Clin. Genet. 68: 61-68, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952988</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00439.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15952988">Margarit et al. (2005)</a> identified a met645-to-arg (M645R) substitution in exon 6 of the ATP7B gene, between the sixth copper-binding domain and the first transmembrane region. The patients were all compound heterozygotes for mutation in the ATP7B gene, and all had the hepatic form of the disease. In 6 patients in whom M645R was combined with a nonsense mutation, there was early onset of the disease, occurring between 5 and 14 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952988" 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">rs137853279 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853279;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=rs137853279" 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=rs137853279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs60431989 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60431989;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/rs60431989?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=rs60431989" 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=rs60431989" 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=RCV000004067 OR RCV000023582 OR RCV000727509 OR RCV001852911 OR RCV002453275" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004067, RCV000023582, RCV000727509, RCV001852911, RCV002453275" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004067...</a>
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<p>In a patient with Wilson disease (WND; <a href="/entry/277900">277900</a>) from a small village in Crete with an unusually high frequency of the disorder, <a href="#4" class="mim-tip-reference" title="Dedoussis, G. V. Z., Genschel, J., Sialvera, T.-E., Bochow, B., Manolaki, N., Manios, Y., Tsafantakis, E., Schmidt, H. <strong>Wilson disease: high prevalence in a mountaineous (sic) area of Crete.</strong> Ann. Hum. Genet. 69: 268-274, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15845031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15845031</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2005.00171.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15845031">Dedoussis et al. (2005)</a> identified compound heterozygosity involving 3 different mutations in the ATP7B gene. An ile1148-to-thr substitution (I1148T) and a gly1176-to-arg substitution (G1176R) cosegregated in cis in the same patient. The other allele of this patient carried a nonsense mutation (Q289X; <a href="#0022">606882.0022</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15845031" 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>.0022 WILSON DISEASE</strong>
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ATP7B, GLN289TER
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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> rs121907999 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907999;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/rs121907999?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=rs121907999" 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=rs121907999" 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=RCV000004068 OR RCV000421016" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004068, RCV000421016" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004068...</a>
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<p>For discussion of the gln289-to-ter (Q289X) mutation in the ATP7B gene that was found in compound heterozygous state in a patient with Wilson disease (WND; <a href="/entry/277900">277900</a>) by <a href="#4" class="mim-tip-reference" title="Dedoussis, G. V. Z., Genschel, J., Sialvera, T.-E., Bochow, B., Manolaki, N., Manios, Y., Tsafantakis, E., Schmidt, H. <strong>Wilson disease: high prevalence in a mountaineous (sic) area of Crete.</strong> Ann. Hum. Genet. 69: 268-274, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15845031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15845031</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2005.00171.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15845031">Dedoussis et al. (2005)</a>, see <a href="#0021">606882.0021</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15845031" 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>.0023 WILSON DISEASE</strong>
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ATP7B, LEU708PRO
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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> rs121908000 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908000;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/rs121908000?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=rs121908000" 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=rs121908000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004069 OR RCV000507833 OR RCV000597397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004069, RCV000507833, RCV000597397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004069...</a>
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<p>In 18 individuals with Wilson disease (WND; <a href="/entry/277900">277900</a>) from the Canary Islands of Spain, <a href="#10" class="mim-tip-reference" title="Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A. <strong>High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.</strong> Hepatology 32: 1329-1336, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11093740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11093740</a>] [<a href="https://doi.org/10.1053/jhep.2000.20152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11093740">Garcia-Villarreal et al. (2000)</a> identified a T-to-C transition in exon 8 of the ATP7B gene, resulting in a leu708-to-pro (L708P) substitution. Twelve patients were homozygous for the mutation. Homozygous patients tended to have a neurologic presentation at an average age of 16 years. Haplotype analysis indicated a founder effect. The L708P mutation was estimated to have arisen in Gran Canaria over 56 generations ago, in pre-Hispanic times. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11093740" 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>.0024 WILSON DISEASE</strong>
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ATP7B, GLY691ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908001 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908001;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=rs121908001" 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=rs121908001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004070</a>
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<p>In 5 affected members of a consanguineous Lebanese family with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#1" class="mim-tip-reference" title="Barada, K., Nemer, G., ElHajj, I. I., Touma, J., Cortas, N., Boustany, R.-M., Usta, J. <strong>Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease. (Letter)</strong> Clin. Genet. 72: 264-267, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17718866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17718866</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00853.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17718866">Barada et al. (2007)</a> identified a homozygous G-to-A transition in exon 7 of the ATP7B gene, resulting in a gly691-to-arg (G691R) substitution in the TM2 domain. Four SNPs in the ATP7B gene were also inherited homozygously with the G691R substitution and may have contributed to altered protein function. Two patients presented at ages 7 and 9 years, respectively, with advanced hepatic cirrhosis. The 3 other affected individuals, who were asymptomatic, were detected by screening before age 14. Four additional family members, 3 of whom were deceased, were reportedly affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17718866" 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="0025" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0025 WILSON DISEASE</strong>
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ATP7B, ILE1148THR
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004067 OR RCV000023582 OR RCV000727509 OR RCV002453275" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004067, RCV000023582, RCV000727509, RCV002453275" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004067...</a>
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<p>In Chinese patients with Wilson disease (WND; <a href="/entry/277900">277900</a>), <a href="#45" class="mim-tip-reference" title="Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M. <strong>Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.</strong> J. Hum. Genet. 56: 660-665, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21796144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21796144</a>] [<a href="https://doi.org/10.1038/jhg.2011.76" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21796144">Wang et al. (2011)</a> identified a 3443T-C transition in exon 16 of the ATP7B gene, resulting in an ile1148-to-thr (I1148T) substitution in the ATP loop of the protein. The I1148T mutation was the second most common mutation among 69 Chinese patients with Wilson disease, accounting for 9.59% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21796144" 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>REFERENCES</strong>
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<a id="Barada2007" class="mim-anchor"></a>
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Barada, K., Nemer, G., ElHajj, I. I., Touma, J., Cortas, N., Boustany, R.-M., Usta, J.
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<strong>Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease. (Letter)</strong>
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Clin. Genet. 72: 264-267, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17718866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17718866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17718866" 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.1399-0004.2007.00853.x" target="_blank">Full Text</a>]
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Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W.
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<strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong>
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Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" 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/ng1293-327" target="_blank">Full Text</a>]
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Cullen, L. M., Prat, L., Cox, D. W.
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<strong>Genetic variation in the promoter and 5-prime UTR of the copper transporter, ATP7B, in patients with Wilson disease.</strong>
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Clin. Genet. 64: 429-432, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14616767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14616767</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14616767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2003.00160.x" target="_blank">Full Text</a>]
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|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Dedoussis2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dedoussis, G. V. Z., Genschel, J., Sialvera, T.-E., Bochow, B., Manolaki, N., Manios, Y., Tsafantakis, E., Schmidt, H.
|
|
<strong>Wilson disease: high prevalence in a mountaineous (sic) area of Crete.</strong>
|
|
Ann. Hum. Genet. 69: 268-274, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15845031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15845031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15845031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1529-8817.2005.00171.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dijkstra1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dijkstra, M., In't Veld, G., van den Berg, G. J., Muller, M., Kuipers, F., Vonk, R. J.
|
|
<strong>Adenosine triphosphate-dependent copper transport in isolated rat liver plasma membranes.</strong>
|
|
J. Clin. Invest. 95: 412-416, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7814642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7814642</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7814642" 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/JCI117670" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Duc1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Duc, H.-H., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G.
|
|
<strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong>
|
|
Europ. J. Hum. Genet. 6: 616-623, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200237" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Figus1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others.
|
|
<strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong>
|
|
Am. J. Hum. Genet. 57: 1318-1324, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533760" 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="8" class="mim-anchor"></a>
|
|
<a id="Firneisz2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Firneisz, G., Lakatos, P. L., Szalay, F., Polli, C., Glant, T. T., Ferenci, P.
|
|
<strong>Common mutations of ATP7B in Wilson disease patients from Hungary.</strong>
|
|
Am. J. Med. Genet. 108: 23-28, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857545" 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/ajmg.10220" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Forbes2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Forbes, J. R., Cox, D. W.
|
|
<strong>Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.</strong>
|
|
Hum. Molec. Genet. 9: 1927-1935, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942420" 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/9.13.1927" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Garcia-Villarreal2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A.
|
|
<strong>High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.</strong>
|
|
Hepatology 32: 1329-1336, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11093740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11093740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11093740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1053/jhep.2000.20152" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gourdon2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gourdon, P., Liu, X.-Y., Skjorringe, T., Morth, J. P., Moller, L. B., Pedersen, B. P., Nissen, P.
|
|
<strong>Crystal structure of a copper-transporting PIB-type ATPase.</strong>
|
|
Nature 475: 59-64, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21716286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21716286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21716286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature10191" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gromadzka2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A.
|
|
<strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.</strong>
|
|
Clin. Genet. 68: 524-532, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16283883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16283883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16283883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2005.00528.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Gu2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gu, Y.-H., Kodama, H., Du, S.-L., Gu, Q.-J., Sun, H.-J., Ushijima, H.
|
|
<strong>Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.</strong>
|
|
Clin. Genet. 64: 479-484, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14986826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14986826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14986826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1399-0004.2003.00179.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gupta2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K.
|
|
<strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong>
|
|
Hum. Genet. 118: 49-57, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16133174" 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/s00439-005-0007-y" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Harris2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harris, E. D.
|
|
<strong>Cellular copper transport and metabolism.</strong>
|
|
Annu. Rev. Nutr. 20: 291-310, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10940336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10940336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10940336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.nutr.20.1.291" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Houwen1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Houwen, R. H. J., Juyn, J., Hoogenraad, T. U., Ploos van Amstel, J. K., Berger, R.
|
|
<strong>H714Q mutation in Wilson disease is associated with late, neurological presentation.</strong>
|
|
J. Med. Genet. 32: 480-482, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7666402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7666402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7666402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.32.6.480" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Kim1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H.
|
|
<strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong>
|
|
Hum. Mutat. 11: 275-278, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554743" 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(1998)11:4<275::AID-HUMU4>3.0.CO;2-L" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kusuda2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kusuda, Y., Hamaguchi, K., Mori, T., Shin, R., Seike, M., Sakata, T.
|
|
<strong>Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.</strong>
|
|
J. Hum. Genet. 45: 86-91, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10721669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10721669</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10721669" 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/s100380050017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="La Fontaine2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
La Fontaine, S., Theophilos, M. B., Firth, S. D., Gould, R., Parton, R. G., Mercer, J. F. B.
|
|
<strong>Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase.</strong>
|
|
Hum. Molec. Genet. 10: 361-370, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11157799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11157799</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11157799" 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/10.4.361" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lim2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lim, C. M., Cater, M. A., Mercer, J. F. B., La Fontaine, S.
|
|
<strong>Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A.</strong>
|
|
J. Biol. Chem. 281: 14006-14014, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16554302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M512745200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Loudianos1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A.
|
|
<strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong>
|
|
Hum. Mutat. 14: 294-303, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502776" 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(199910)14:4<294::AID-HUMU4>3.0.CO;2-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Loudianos1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M.
|
|
<strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong>
|
|
Hum. Mutat. 12: 89-94, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9671269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9671269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9671269" 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(1998)12:2<89::AID-HUMU3>3.0.CO;2-G" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Loudianos2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loudianos, G., Lovicu, M., Dessi, V., Tzetis, M., Kanavakis, E., Zancan, L., Zelante, L., Galvez-Galvez, C., Cao, A.
|
|
<strong>Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B.</strong>
|
|
Hum. Mutat. 20: 260-266, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12325021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12325021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12325021" 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.10121" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Loudianos2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loudianos, G., Lovicu, M., Solinas, P., Kanavakis, E., Tzetis, M., Manolaki, N., Panagiotakaki, E., Karpathios, T., Cao, A.
|
|
<strong>Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.</strong>
|
|
Genet. Test. 4: 399-402, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11216666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11216666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11216666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1089/109065700750065162" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Luoma2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Luoma, L. M., Deeb, T. M., Macintyre, G., Cox, D. W.
|
|
<strong>Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.</strong>
|
|
Hum. Mutat. 31: 569-577, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20333758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20333758</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20333758" 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.21228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Margarit2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F.
|
|
<strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong>
|
|
Clin. Genet. 68: 61-68, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2005.00439.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Okada2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H.
|
|
<strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.</strong>
|
|
Hum. Mutat. 15: 454-462, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790207" 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(200005)15:5<454::AID-HUMU7>3.0.CO;2-J" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Panagiotakaki2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E.
|
|
<strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong>
|
|
Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523622</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523622" 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/ajmg.a.30345" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Park2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W.
|
|
<strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong>
|
|
Clin. Genet. 75: 405-407, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19419418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19419418</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2008.01132.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Park2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W.
|
|
<strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong>
|
|
Hum. Mutat. 28: 1108-1113, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17587212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17587212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17587212" 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.20574" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Payne1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Payne, A. S., Kelly, E. J., Gitlin, J. D.
|
|
<strong>Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 10854-10859, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9724794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9724794</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9724794[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9724794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.95.18.10854" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Pendlebury2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pendlebury, S. T., Rothwell, P. M., Dalton, A., Burton, E. A.
|
|
<strong>Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation.</strong>
|
|
Neurology 63: 1982-1983, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557537</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000144192.30426.38" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Petrukhin1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petrukhin, K. E., Lutsenko, S., Chernov, I., Ross, B. M., Kaplan, J. H., Gilliam, T. C.
|
|
<strong>Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions.</strong>
|
|
Hum. Molec. Genet. 3: 1647-1656, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7833924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7833924</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7833924" 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/3.9.1647" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Reed1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reed, V., Williamson, P., Bull, P. C., Cox, D. W., Boyd, Y.
|
|
<strong>Mapping of the mouse homologue of the Wilson disease gene to mouse chromosome 8.</strong>
|
|
Genomics 28: 573-575, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490097</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490097" 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.1995.1191" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Sasaki1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N.
|
|
<strong>The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 202: 512-518, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8037756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8037756" 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/bbrc.1994.1958" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Shah1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shah, A. B., Chernov, I., Zhang, H. T., Ross, B. M., Das, K., Lutsenko, S., Parano, E., Pavone, L., Evgrafov, O., Ivanova-Smolenskaya, I. A., Anneren, G., Westermark, K., Urrutia, F. H., Penchaszadeh, G. K., Sternlieb, I., Scheinberg, I. H., Gilliam, T. C., Petrukhin, K.
|
|
<strong>Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation and functional analyses.</strong>
|
|
Am. J. Hum. Genet. 61: 317-328, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/514864" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Takeshita2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T.
|
|
<strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong>
|
|
J. Hum. Genet. 47: 543-547, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s100380200082" target="_blank">Full Text</a>]
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|
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|
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|
|
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|
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<a id="38" class="mim-anchor"></a>
|
|
<a id="Tanzi1993" class="mim-anchor"></a>
|
|
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|
|
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Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C.
|
|
<strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong>
|
|
Nature Genet. 5: 344-350, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" 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/ng1293-344" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
|
<a id="39" class="mim-anchor"></a>
|
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<a id="Terada1998" class="mim-anchor"></a>
|
|
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|
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|
|
Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T.
|
|
<strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong>
|
|
J. Biol. Chem. 273: 1815-1820, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.273.3.1815" target="_blank">Full Text</a>]
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<a id="40" class="mim-anchor"></a>
|
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<a id="Thomas1995" class="mim-anchor"></a>
|
|
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|
|
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|
|
Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
|
|
<strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong>
|
|
Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" 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/ng0295-210" target="_blank">Full Text</a>]
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|
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|
|
Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W.
|
|
<strong>Wilson disease in Iceland: a clinical and genetic study.</strong>
|
|
Am. J. Hum. Genet. 56: 1140-1146, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
|
|
<strong>Haplotypes and mutations in Wilson disease.</strong>
|
|
Am. J. Hum. Genet. 56: 1315-1319, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
<a id="43" class="mim-anchor"></a>
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|
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Todorov, T., Savov, A., Jelev, H., Panteleeva, E., Konstantinova, D., Krustev, Z., Mihaylova, V., Tournev, I., Tankova, L., Tzolova, N., Kremensky, I.
|
|
<strong>Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. (Letter)</strong>
|
|
Clin. Genet. 68: 474-476, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16207219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16207219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16207219" 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.1399-0004.2005.00516.x" target="_blank">Full Text</a>]
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|
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Wallace, D. F., Dooley, J. S.
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<strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong>
|
|
Hum. Genet. 139: 1065-1075, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32248359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32248359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32248359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-020-02161-3" target="_blank">Full Text</a>]
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|
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Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M.
|
|
<strong>Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.</strong>
|
|
J. Hum. Genet. 56: 660-665, 2011.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21796144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21796144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21796144" 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.2011.76" target="_blank">Full Text</a>]
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|
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|
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Wilson, D. C., Phillips, M. J., Cox, D. W., Roberts, E. A.
|
|
<strong>Severe hepatic Wilson's disease in preschool-aged children.</strong>
|
|
J. Pediat. 137: 719-722, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11060541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11060541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11060541" 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/10.1067/mpd.2000.108569" target="_blank">Full Text</a>]
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Wu, Z.-Y., Wang, N., Lin, M.-T., Fang, L., Murong, S.-X., Yu, L.
|
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<strong>Mutation analysis and the correlation between genotype and phenotype of arg778leu mutation in Chinese patients with Wilson disease.</strong>
|
|
Arch. Neurol. 58: 971-976, 2001.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11405812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11405812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11405812" 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/10.1001/archneur.58.6.971" target="_blank">Full Text</a>]
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Yang, X.-L., Miura, N., Kawarada, Y., Terada, K., Petrukhin, K., Gilliam, T. C., Sugiyama, T.
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<strong>Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.</strong>
|
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Biochem. J. 326: 897-902, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9307043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9307043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9307043" 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/10.1042/bj3260897" target="_blank">Full Text</a>]
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Yoo, H. W.
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<strong>Identification of novel mutations and the 3 most common mutations in the human ATP7B gene of Korean patients with Wilson disease.</strong>
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Genet. Med. 4: 43S-48S, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12544487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12544487</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12544487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/00125817-200211001-00009" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/03/2021
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Patricia A. Hartz - updated : 8/9/2012<br>Cassandra L. Kniffin - updated : 11/1/2011<br>Ada Hamosh - updated : 9/6/2011<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 8/30/2010<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Cassandra L. Kniffin - updated : 10/26/2007<br>Cassandra L. Kniffin - updated : 3/21/2007<br>Marla J. F. O'Neill - updated : 10/25/2006<br>Marla J. F. O'Neill - updated : 12/28/2005<br>Cassandra L. Kniffin - updated : 12/9/2005<br>Patricia A. Hartz - updated : 11/10/2005<br>Victor A. McKusick - updated : 8/19/2005<br>Marla J. F. O'Neill - updated : 7/5/2005<br>Cassandra L. Kniffin - updated : 3/15/2005<br>Victor A. McKusick - updated : 1/14/2005<br>Victor A. McKusick - updated : 1/12/2004<br>Victor A. McKusick - updated : 12/4/2003<br>Ada Hamosh - updated : 3/4/2003<br>Victor A. McKusick - updated : 1/7/2003<br>Victor A. McKusick - updated : 11/1/2002<br>Cassandra L. Kniffin - updated : 9/6/2002
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Cassandra L. Kniffin : 4/25/2002
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carol : 02/04/2021<br>carol : 02/03/2021<br>carol : 03/26/2020<br>carol : 03/25/2020<br>carol : 10/18/2016<br>carol : 05/04/2015<br>mcolton : 5/4/2015<br>carol : 12/19/2013<br>terry : 11/6/2012<br>mgross : 8/10/2012<br>terry : 8/9/2012<br>carol : 8/8/2012<br>carol : 11/1/2011<br>ckniffin : 11/1/2011<br>alopez : 9/7/2011<br>terry : 9/6/2011<br>carol : 8/5/2011<br>wwang : 12/29/2010<br>ckniffin : 12/3/2010<br>wwang : 9/3/2010<br>ckniffin : 8/30/2010<br>wwang : 11/14/2008<br>mgross : 3/10/2008<br>wwang : 12/14/2007<br>ckniffin : 11/14/2007<br>wwang : 11/6/2007<br>ckniffin : 10/26/2007<br>wwang : 4/4/2007<br>ckniffin : 3/21/2007<br>wwang : 11/7/2006<br>wwang : 10/26/2006<br>terry : 10/25/2006<br>wwang : 1/5/2006<br>terry : 12/28/2005<br>wwang : 12/9/2005<br>ckniffin : 12/7/2005<br>mgross : 11/16/2005<br>terry : 11/10/2005<br>wwang : 9/1/2005<br>wwang : 8/25/2005<br>terry : 8/19/2005<br>wwang : 7/11/2005<br>wwang : 7/11/2005<br>terry : 7/5/2005<br>ckniffin : 3/15/2005<br>wwang : 1/27/2005<br>wwang : 1/25/2005<br>alopez : 1/25/2005<br>wwang : 1/20/2005<br>terry : 1/14/2005<br>carol : 1/20/2004<br>terry : 1/12/2004<br>alopez : 12/10/2003<br>terry : 12/4/2003<br>cwells : 3/4/2003<br>cwells : 3/4/2003<br>cwells : 1/8/2003<br>tkritzer : 1/7/2003<br>tkritzer : 11/4/2002<br>terry : 11/1/2002<br>carol : 9/10/2002<br>ckniffin : 9/6/2002<br>terry : 5/20/2002<br>ckniffin : 4/29/2002<br>carol : 4/29/2002<br>ckniffin : 4/29/2002
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<span class="mim-font">
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<strong>*</strong> 606882
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<h3>
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<span class="mim-font">
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ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<h4>
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<span class="mim-font">
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ATPase COPPER TRANSPORTING BETA<br />
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WND
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ATP7B</em></strong>
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</span>
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</p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 190823004, 88518009;
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<strong>ICD10CM:</strong> E83.01;
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<strong>
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<em>
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Cytogenetic location: 13q14.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:51,932,669-52,012,132 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<td rowspan="1">
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<span class="mim-font">
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13q14.3
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<span class="mim-font">
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Wilson disease
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<td>
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<span class="mim-font">
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277900
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
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<p>The ATP7B gene encodes a polypeptide that acts as a plasma membrane copper-transport protein (summary by Harris, 2000). </p>
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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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<p>On YACs from the 13q14.3 region, Bull et al. (1993) identified a sequence similar to that coding for the proposed copper-binding regions of the putative ATPase gene defective in Menkes disease (MNK; 309400). They showed that this sequence forms part of a P-type ATPase gene that is very similar to MNK, with 6 putative metal-binding regions similar to those found in prokaryotic heavy metal transporters. The gene, designated ATP7B, is expressed in liver and kidney, and was found to lie within a 300-kb region likely to include the Wilson disease locus (WND; 277900). The identity between MNK and the newly identified ATP7B gene was 78% in the transduction region, 89% in the channel/phosphorylation regions, and 79% in the ATP-binding region. The predicted length of the gene product was 1,411 amino acids for ATP7B compared with 1,500 amino acids for MNK. The overall identity between the two was 57%. </p><p>Tanzi et al. (1993) used consensus DNA sequences for heavy metal binding motifs to identify homologous cDNA clones. One of these was mapped by PCR amplification and Southern blotting to contiguous YAC and cosmid clones that span the WND locus at chromosome 13q14.3. The cDNA detected a 7.5-kb RNA transcript expressed most strongly in liver and brain. Sequence analysis indicated several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. The deduced protein showed 62% amino acid homology to the Menkes disease gene. </p><p>Yang et al. (1997) stated that the full-length ATP7B protein contains 1,465 amino acids. They cloned a splice variant of ATP7B lacking exons 6, 7, 8, and 12 from a human brain cDNA library. The deduced protein contains 1,258 amino acids. Immunofluorescence localization and fractionation of a hepatoma cell line revealed that the full-length protein was associated with the Golgi apparatus and the shorter isoform was cytosolic. Full-length ATP7B did not redistribute in response to elevated copper levels, and it did not associate with the plasma membrane. </p>
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<strong>Gene Function</strong>
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</h4>
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<span class="mim-text-font">
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<p>Tanzi et al. (1993) noted that the protein encoded by the ATP7B gene had the characteristics of a copper-transporting ATPase. They suggested that it may serve a function in the export of copper from cells, whereas the Menkes gene product has a role in the import of copper. Dijkstra et al. (1995) studied copper transport in rat liver plasma membranes and suggested that the ATP7B protein functions to transport copper across these membranes in the presence of ATP. Harris (2000) reviewed cellular copper transport and metabolism and stated that the ATP7B protein resides within internal compartments of the cell, where it may function to incorporate copper into apo-ceruloplasmin, and to release copper into bile. </p><p>Lim et al. (2006) stated that ATP7B localizes to the trans-Golgi network, where it transports copper to apoceruloplasmin (CP; 117700). When copper levels are in excess, ATP7B redistributes to a vesicular compartment near the biliary canalicular membranes for elimination of excess copper into bile. Using a yeast 2-hybrid screen of a human liver cDNA library, Lim et al. (2006) found that the N-terminal domain of ATP7B, which contains 6 metal-binding motifs, interacted with the C-terminal domain of the p62 dynactin subunit (DCTN4; 614758). Coimmunoprecipitation analysis revealed that ATP7B, but not ATP7A (300011), interacted with endogenous p62 in a human fibroblast line. Depletion of copper reduced interaction of ATP7B with p62. Mutation analysis revealed that the metal-binding CxxC motifs of ATP7B were required for interaction with p62, predominantly CxxC motifs 4 through 6. Lim et al. (2006) concluded that ATP7B is transported along liver cell microtubules in a copper-dependent manner via interaction with the p62 dynactin subunit. </p><p><strong><em>Variant Proteins</em></strong></p><p>
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Forbes and Cox (2000) analyzed the intracellular localization of ATP7B variant proteins using transient transfection and triple-label immunofluorescence microscopy. Two human WND ATP7B variants, asp765 to asn (606882.0012) and leu776 to val, which have normal copper transport activity in yeast, retained partial normal Golgi network localization, but were predominantly mislocalized throughout the cell and were capable of only partial copper-dependent redistribution. Variant protein arg778 to leu (R778L; 606882.0009), which has defective function in yeast, was extensively mislocalized, presumably to the endoplasmic reticulum. Variant proteins gly943 to ser (606882.0013), which has nearly normal function in yeast, and cys-pro-cys/ser (mutation of the conserved cys-pro-cys motif to ser-pro-ser), which is inactive in yeast, were localized normally but were unable to redistribute in response to copper. The authors hypothesized that mislocalization and/or deficient copper transport are defects seen in some mutant proteins, and that the nature of the malfunction(s) may explain, in part, the variable biochemical features of WND, in particular the normal holoceruloplasmin levels observed in some patients. </p><p>La Fontaine et al. (2001) generated cDNA constructs encoding the wildtype (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) and expressed them in Chinese hamster ovary (CHO) cells. The tx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, colocalization experiments demonstrated that while Wnd and MNK (309400) are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell. Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multivesicular structures resembling late endosomes that may represent a novel compartment for copper transport. </p><p>Luoma et al. (2010) generated yeast deficient in Ccc2, the ortholog of ATP7B, and used the Ccc2-deficient yeast model system to test the functional effect of 12 ATP7B missense variants that localize to the ATP loop of the protein. These variants may affect binding of ATP, autophosphorylation, or folding of the protein. Variants L1043P, G1000R, G1101R, I1102T, V1239G, and D1267V were found to be deleterious; G1176E and G1287S were intermediate; E1173G were temperature-sensitive; and T991M and I1148T were mild. The R1228T variant functioned similar to wildtype protein. Comparison of the functional data from the yeast model system with 3 predictive programs indicated that SIFT was most accurate (92%) followed by PolyPhen (83%) and Align-GVGD (67%). </p>
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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>Yang et al. (1997) determined that the ATP7B gene contains 21 exons. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bull et al. (1993) identified the ATP7B gene in the Wilson disease critical region on chromosome 13q14.3. </p><p>Sasaki et al. (1994) identified the rat homolog of the human Wilson disease gene as the gene responsible for hepatitis (hts) in the Long Evans Cinnamon rat. They mapped the rat Wnd gene to 16q12.23-q12.3 by fluorescence in situ hybridization and mouse/rat somatic cell hybrid analysis. </p><p>Reed et al. (1995) mapped the homolog of ATP7B to mouse chromosome 8 by somatic cell hybrid analysis. Interspecific backcross analysis showed that Atp7b is close to D8Mit3 and Atp4b, another ATPase gene. Interestingly, human ATP7B occurs in a region of conserved synteny with mouse chromosome 14. </p>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Gourdon et al. (2011) presented the structure of a P-type class IB (PIB) ATPase, a Legionella pneumophila CopA copper ATPase, in a copper-free form, as determined by x-ray crystallography at 3.2-angstrom resolution. The structure indicates a 3-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to calcium ATPase suggested an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. Gourdon et al. (2011) suggested that their structure will provide a framework for analysis of missense mutations in human ATP7A and ATP7B proteins associated with Menkes disease and Wilson disease, respectively. </p>
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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 class="mim-text-font">
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<p>Bull et al. (1993) reported 2 patients with Wilson disease (WND; 277900) who were found to be homozygous for a 7-bp deletion within the coding region of the ATP7B gene (606882.0001). Tanzi et al. (1993) noted that a lysine-to-arginine mutation near the phosphorylation site of the ATPase occurred in 85% of all WND chromosomes analyzed and in only 15% of 'normal' chromosomes in diverse populations. Tanzi et al. (1993) identified 4 mutations in unrelated persons with Wilson disease: 2 missense mutations and 2 frameshift mutations resulting in a truncated gene product (606882.0002-606882.0005). The mutations were found among 50 unrelated families derived predominantly from the United States, 18 unrelated families from Russia, and 5 presumably unrelated families from Sicily. Clearly, Bull et al. (1993) and Tanzi et al. (1993) had independently isolated the same gene which was convincingly the one mutant in Wilson disease. </p><p>Thomas et al. (1995) reviewed the mutations found in the ATP7B gene. In 58 patients with Wilson disease, they found 20 new mutations as well as 3 of the 5 previously published mutations: 11 small insertions and deletions, 7 missense mutations, 2 nonsense mutations, and 3 splice site mutations. Two of the mutations, his1070 to gly (606882.0006) and gly1267 to arg (606882.0007), are relatively frequent, together accounting for 38% of mutations in patients of European origin. Their findings suggested a wide span in the age of onset of Wilson disease, perhaps wider than previously considered typical. Mutations that completely disrupt the gene can produce liver disease in early childhood at a time when Wilson disease may not be considered in the differential diagnosis. </p><p>Given the difficulties of searching for mutations in a gene spanning more than 80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. Thomas et al. (1995) did haplotyping of the Wilson disease gene region in 58 families. These haplotypes, combining 3 markers (D13S314, D13S316, and D13S301), were usually specific for each different mutation. The haplotype data suggested that as many as 20 mutations might still be unidentified; a total of 25 disease-causing mutations had been identified at that time. </p><p>Figus et al. (1995) identified 16 novel mutations in 127 affected patients of Mediterranean descent: 8 frameshifts, 7 missense mutations, and 1 splicing defect. In addition, they detected 5 previously described mutations, e.g., his1070-to-gln (606882.0006), which accounted for 13% of the mutations in WND chromosomes in non-Sardinian Mediterranean populations. </p><p>Loudianos et al. (1999) characterized the putative promoter and 5-prime untranslated region of the WD gene and carried out mutation analysis in this region in Sardinian WD patients with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion (606882.0010) in all chromosomes with this common haplotype. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. </p><p>Loudianos et al. (1998) performed a mutation screen on the WND gene in 59 patients of Mediterranean origin: 26 Continental Italians, 22 Sardinians, 9 Turkish, and 2 Albanians. They found 31 novel and 3 known mutations. Most of the patients were compound heterozygotes. </p><p>Kim et al. (1998) identified 3 novel mutations in the ATP7B gene in Korean patients with Wilson disease. One of these, arg778 to leu (R778L; 606882.0009), was found in 6 of 8 unrelated patients, giving an allele frequency of 37.5%. </p><p>Duc et al. (1998) performed mutation analysis in 33 German and 10 Cuban unrelated Wilson disease patients. The common his1069-to-gln (606882.0006) mutation accounted for 42% of all WND chromosomes in the German series and haplotype C was found to be highly predictive for this mutation. Six previously undescribed WND gene mutations were identified. In 15 German WND index patients and 3 sibs, both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the his1069-to-gln mutation showed almost a complete range of clinical presentations; thus, in this study, the his1069-to-gln mutation was not associated with a late neurologic presentation. </p><p>Okada et al. (2000) analyzed the ATP7B gene in 41 unrelated Japanese Wilson disease families, including 47 patients. They identified 21 mutations, 9 of which were novel. </p><p>In 84 Chinese patients with Wilson disease from 65 unrelated families, Wu et al. (2001) identified 18 mutations (7 novel) and 11 polymorphisms (3 novel) in the ATB7B gene. The most common mutations were R778L and T935M, which were present at a frequency of 37.7% and 10.0%, respectively. </p><p>Loudianos et al. (2002) stated that more than 200 Wilson disease-causing mutations had been defined, most of which were missense mutations, while splice site mutations were limited in number. </p><p>Yoo (2002) studied 37 patients from 33 unrelated Korean families with Wilson disease and identified 12 different mutations, of which 6 were novel. The R778L mutation, which is known to be highly prevalent in Asian patients, was found with a frequency of 37.9% among the Korean population, which is significantly higher than that among the Japanese and Taiwanese. The N1270S mutation (606682.0017), which is presumed to disrupt the ATP hinge domain of the ATP7B protein, was the next most common mutation in Korean patients, with an allele frequency of 12.1%. The A874V mutation (606682.0016) was the third most common, accounting for 9.4%. </p><p>Panagiotakaki et al. (2004) analyzed the results of molecular analysis on a cohort that included 93 index patients with Wilson disease from 69 unrelated families in Greece. Detailed phenotypic evaluation was added to the findings reported previously by Loudianos et al. (1998, 2000). Twenty different mutations accounted for 86% of the WND chromosomes. The 2 most common mutations were H1069Q (606882.0006), found in 35% of WND chromosomes, and R969Q (606882.0018), found in 12%. Homozygosity for H1069Q was found in 13 patients and for R969Q in 7. </p><p>Margarit et al. (2005) analyzed 40 unrelated Spanish patients with Wilson disease and identified 21 different mutations in the ATP7B gene in 35 (87%) patients. The M645R (606882.0020) mutation was particularly prevalent and was found in 22 patients (55%), who were all compound heterozygotes for mutation in the ATP7B gene. </p><p>Dedoussis et al. (2005) observed an increased number of WD patients on the island of Crete and studied the spectrum of mutations in a small village close to the city of Heraklion. Of 90 births in the village since 1978, 6 were found to have WD. Analysis of the entire gene in 3 WD patients and in relatives of a boy who died from WD led to the detection of 4 different mutations. Two missense mutations (see 606882.0021) cosegregated in cis in the same patient. The other allele of this patient carried a nonsense mutation (606882.0022). This was said to have been the first report of 3 mutations cosegregating in the same WD patient. The fourth mutation identified was a novel frameshift mutation with documented cosegregation with WD. A screen of 200 inhabitants originating from the same area demonstrated that 18 were carriers of one of these mutations. </p><p>Gupta et al. (2005) analyzed Indian patients with Wilson disease from 62 unrelated families and their first-degree relatives and identified a total of 9 mutations, 5 novel, in the ATP7B gene. The authors noted that homozygotes for different mutations that would be expected to produce similar defective proteins showed significant disparity in terms of organ involvement and severity of disease; in 1 family, 2 sibs with the same pair of mutant chromosomes had remarkably different phenotypes. Gupta et al. (2005) suggested that there may be as yet unidentified modifying loci that account for the observed phenotypic heterogeneity among patients with Wilson disease. </p><p>In 120 unrelated Korean patients with Wilson disease, Park et al. (2007) identified 28 different mutations, including 6 novel mutations, in the ATP7B gene. R778L was the most common mutation, occurring in 39.2% of mutant alleles. Functional studies of some of the mutant proteins in yeast cells and COS-7 cells showed impaired copper transport and aberrant cellular localization of mutant ATP7B proteins. </p><p>Wallace and Dooley (2020) found that of the 732 Wilson disease-associated ATP7B mutations reported by 2017, most (55%) were missense mutations. Of the 732 mutations, 231 were present in the gnomAD database, giving an initial estimated population prevalence of 1 in 2,400. Wallace and Dooley (2020) assessed the penetrance/pathogenicity of ATP7B mutations by comparing gnomAD allele frequencies with the number of reports of each mutation and then using a variant effect prediction algorithm. When the authors reassessed the pathogenic allele frequency of ATP7B mutations excluding those likely to have low penetrance, they calculated the population prevalence of Wilson disease to be 1 in 20,000 individuals. </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>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">
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<p>Panagiotakaki et al. (2004) studied a Wilson disease cohort that included 93 Greek index patients from 69 unrelated families and reported that the H1069Q and R969Q mutations appeared to confer a milder disease as patients showed disease onset at a later age and also were associated with milder severity when found in trans (compound heterozygosity) with severe mutations. Predicted nonsense and frameshift mutations were associated with severe phenotypic expression with earlier disease onset and lower ceruloplasmin values. Panagiotakaki et al. (2004) noted that their findings on the phenotypic effect of predicted nonsense and frameshift mutations were especially important for early medical intervention in presymptomatic infants and children with these genotypes. </p><p>Gromadzka et al. (2005) studied 142 Polish patients with Wilson disease and identified 26 mutations in the ATP7B gene: 11 truncating, 14 missense, and 1 splice site mutation. Patients with 1 or 2 truncating mutations had lower serum copper and ceruloplasmin levels and were younger when the first symptoms of the disease appeared compared with individuals with 2 missense mutations, and the effect of truncating mutations on phenotype was dose-dependent. Gromadzka et al. (2005) found no association between type of ATP7B mutation and mode of initial disease presentation (neurologic, hepatic, or mixed). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Terada et al. (1998) introduced human ATP7B cDNA into the LEC rat using recombinant adenovirus-mediated gene delivery. An immunofluorescence study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LEC rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of ATP7B protein with respect to copper transport. Holoceruloplasmin was found in plasma of LEC rats who received ATP7B cDNA. Terada et al. (1998) concluded that introduced ATP7B protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for ATP7B protein to manifest its function. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>25 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, 7-BP DEL, NT2010
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<br />
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SNP: rs779904655,
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gnomAD: rs779904655,
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ClinVar: RCV000169214, RCV002274945
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>To confirm the conclusion that the gene they identified in a YAC from the 13q14.3 region and referred to as Wc1 was indeed the gene mutated in Wilson disease (WND; 277900), Bull et al. (1993) studied 30 patients with the disorder selected to represent 29 different haplotypes based on 3 close markers. Using 3 cDNA fragments and 3 restriction enzymes, they found no altered fragments or dosage differences indicative of gross deletions. Single-strand conformation polymorphism analysis and heteroduplex analysis were performed in 27 patients. Both methods revealed a particular band shift, which on sequencing was found to represent homozygosity for the same 7-bp deletion, removing bases 1950-1956 of their sequence, causing a frameshift that resulted in an immediate stop codon at position 639 in the amino acid sequence, and removing the entire C-terminal half of the protein. </p><p>The name of the 7-bp deletion (1950del7), originally described by Bull et al. (1993), was changed to 2010del7 to be consistent with the position of the ATG start codon identified by Petrukhin et al. (1994). The same mutation was found by Thomas et al. (1995) in affected members of 2 large kindreds in Iceland. Haplotype data and the nature of the mutation supported the existence of a founder chromosome. Although the protein function was predicted to be completely abolished by the deletion, predicting early-onset liver disease, Thomas et al. (1995) found that the patients presented with later-onset neurologic and psychiatric symptoms. They showed that alternative splicing of the transcript in the region of the deletion may have contributed to later onset, suggesting that alternative isoforms of the protein may have functional significance. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, HIS714GLN
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<br />
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SNP: rs76151636,
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gnomAD: rs76151636,
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ClinVar: RCV000004052, RCV000078049, RCV002321470
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 31% of Wilson disease (WND; 277900) chromosomes in 50 unrelated Americans and in 22% of Wilson disease chromosomes in 18 unrelated Russian families, Tanzi et al. (1993) found a C-to-A transversion at nucleotide 2142 in the ATP7B gene, causing a substitution of glutamine for histidine-714 in the phosphorylation domain of the protein. Houwen et al. (1995) analyzed 38 Dutch symptomatic Wilson disease patients for the H714Q mutation. Ten patients homozygous for the mutation presented at a mean age of 20.3 (SD 6.1) years, with either neurologic symptoms or a Kayser-Fleischer ring. Six patients with the H714Q mutation in one chromosome and an unknown mutation in the other chromosome presented at a mean age of 17.8 (SD 5.8) years, with either neurologic or hepatic symptoms. With the exception of 1, all 22 patients with an uncharacterized mutation in both chromosomes presented with liver involvement at a mean age of 9.9 (SD 2.4) years. The findings suggest that the H714Q mutation is a relatively mild one, possibly with some residual function in the copper transporting protein, resulting in a slower build-up of copper. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, ASN915SER
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<br />
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SNP: rs121907990,
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gnomAD: rs121907990,
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ClinVar: RCV000004063, RCV000196058, RCV000504595, RCV000595271, RCV002354147, RCV003904803
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Sicilian case of Wilson disease (WND; 277900), Tanzi et al. (1993) found an A-to-G transition at nucleotide 2744, resulting in substitution of serine for asparagine-915 in the hinge region of the ATP-binding site. This region is highly conserved in all P-type ATPases. The Sicilian patient was homozygous for the mutation and was also homozygous for a 6-marker haplotype that had not been observed in other individuals in their sample of 115 Wilson disease families. Thus, it appears to be a rare mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, 1-BP DEL, 2337C
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<br />
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SNP: rs137853281,
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gnomAD: rs137853281,
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ClinVar: RCV000169026, RCV000523051, RCV004965273
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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 Russian patients with Wilson disease (WND; 277900), Tanzi et al. (1993) found homozygosity for a single basepair deletion, a cytosine at position 2337. This resulted in a frameshift at amino acid 779. In both families, the parents were heterozygous for the mutation, as was a single unaffected sib. The mutation accounted for approximately 20% of Wilson disease chromosomes in a sample of 18 unrelated Russian families. It was found once in an American sample of 50 unrelated families. It was predicted that the mutation would truncate the Wilson disease protein within the phosphorylation region, thereby disabling its function in persons homozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 WILSON DISEASE</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, 1-BP INS, NT2487
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<br />
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SNP: rs748924063,
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gnomAD: rs748924063,
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ClinVar: RCV000169520
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>On 1 chromosome of an American patient with Wilson disease (WND; 277900), Tanzi et al. (1993) found insertion of an extra thymine residue after thymine 2487, resulting in a frameshift at amino acid 829. The change in the protein was in the amphiphilic helix between the phosphorylation and ATP-binding domains. The second disease allele in this patient had not been identified. </p>
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</span>
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</div>
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<div>
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<br />
|
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 WILSON DISEASE</strong>
|
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</span>
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
ATP7B, HIS1069GLN
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<br />
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|
|
SNP: rs76151636,
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|
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gnomAD: rs76151636,
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|
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ClinVar: RCV000004052, RCV000078049, RCV002321470
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|
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a study of 58 patients with Wilson disease (WND; 277900), Thomas et al. (1995) found that 28% had a mutation that they referred to as H1070Q (HIS1070GLN), located in the loop motif and disrupting ATP binding. The patients (19 in number) were of Eastern European, German, French, and British extraction. This mutation was homozygous in 6 families; there was variation in age of onset within these families and an equal number of hepatic and neurologic cases. The average age of onset of symptoms in patients homozygous for the mutation was 16.8 years. The same mutation was found in heterozygous state (compound heterozygotes) in 9 families with a total of 11 patients, with an average age of onset of 17.3 years. Figus et al. (1995) concluded that this mutation is probably the most common molecular defect of the WND gene and may have arisen as a single and very ancient mutation event. </p><p>Payne et al. (1998) stated that the H1069Q mutation represents up to 37% of Wilson disease alleles in patients of Eastern European descent and studied the function of the ATP7B protein by expressing wildtype and mutant ATP7B cDNAs in a Menkes copper transporter-deficient 'mottled' fibroblast cell line defective in copper export. Expression of the wildtype cDNA demonstrated trans-Golgi network localization and copper-dependent trafficking of the ATP7B protein identical to previous observations for the endogenously expressed protein in hepatocytes. Furthermore, expression of the ATP7B cDNA rescued the 'mottled' phenotype as evidenced by a reduction in copper accumulation and restoration of cell liability. In contrast, expression of an H1069Q mutant ATP7B cDNA did not rescue the 'mottled' phenotype, and immunofluorescence studies showed that this mutant ATP7B protein was localized in the endoplasmic reticulum. Pulse-chase analysis demonstrated a 5-fold decrease in the half-life of the H1069Q mutant as compared with the wildtype protein. Maintenance of these transfected cell lines at 28 degrees C resulted in localization of the H1069Q protein in the trans-Golgi network, suggesting that a temperature-sensitive defect in protein folding followed by degradation constitutes the molecular basis of Wilson disease in patients harboring the H1069Q mutation. The results provided compelling evidence that the ATP7B protein can functionally substitute for the Menkes disease protein, ATP7A, supporting the concept that these proteins use common biochemical mechanisms to effect cellular copper homeostasis. </p><p>Duc et al. (1998) found this mutation in 42% of WND chromosomes in a series of 33 German cases of Wilson disease. Haplotype C was highly predictive for this mutation. Patients homozygous for the mutation showed almost a complete range of clinical presentations; in this series, the his1069-to-gln mutation was not associated with a late neurologic presentation. </p><p>Firneisz et al. (2002) found the H1069Q mutation in 27 Hungarian patients with Wilson disease, 64.3% of their series. In 9 of the 27 patients, H1069Q was homozygous. They found that H1069Q-positive patients from various European countries had the same haplotype pattern. Thus the H1069Q mutation appears to have originated from a single founder, at least in Europe. </p><p>Among 80 unrelated Bulgarian families with Wilson disease, Todorov et al. (2005) found that the H1069Q mutation was the most common mutation with an allelic frequency of 58.75%. All 15 families of the Roma ethnic group had the H1069Q mutation, consistent with the Roma being a genetic isolate with frequent consanguinity and endogamy. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 WILSON DISEASE</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, GLY1267ARG
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<br />
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SNP: rs121907992,
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gnomAD: rs121907992,
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|
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ClinVar: RCV000004053, RCV001507825
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a series of 58 patients with Wilson disease (WND; 277900), Thomas et al. (1995) found that 7 (10%), of French and British extraction, had a gly1267-to-arg mutation. Located in the ATP hinge domain, the mutation disrupted the hinge. (The article by Thomas et al. (1995) listed this mutation as GLY1267LYS; a published correction provided the proper amino acid substitution.) </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0008 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, IVS4AS, G-C, -1
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<br />
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SNP: rs137853280,
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gnomAD: rs137853280,
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ClinVar: RCV000004054, RCV001579816
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a series of 58 patients with Wilson disease (WND; 277900), Thomas et al. (1995) found 4 with mutations predicted to destroy the function of the gene (insertion, deletion, nonsense, or frameshift). The average age of onset in these cases was 7 years. Most striking was the age of onset of a patient homozygous for a G-to-C transversion at nucleotide 1711. The patient, of American Indian extraction, presented with liver disease at 3 years of age. The mutation at the acceptor splice site of intron 4 resulted in the deletion of exon 5 and the removal of 54 amino acids, including the last copper-binding domain, from the protein product. </p><p>Wilson et al. (2000) reported a 3-year-old Indo-Pakistani girl, born to consanguineous parents, who was diagnosed with Wilson disease after presenting with hemolytic anemia, hepatosplenomegaly, ascites, and evidence of decompensated chronic liver disease. DNA analysis revealed that she was homozygous for the IVS4-1G-C mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0009 WILSON DISEASE</strong>
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</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, ARG778LEU
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<br />
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SNP: rs28942074,
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|
|
gnomAD: rs28942074,
|
|
|
|
|
|
ClinVar: RCV000004056, RCV000389880, RCV002444420, RCV003398441
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Kim et al. (1998) found a CGG-to-CTG transversion in exon 8 of the ATP7B gene, leading to an arg778-to-leu (R778L) amino acid substitution in 6 of 8 unrelated Korean patients with Wilson disease (WND; 277900). They cited the allele frequency as 37.5% and quoted previous findings indicating a considerable frequency of this allele in Japanese (27.7%), Taiwanese (27%), and Chinese (11.1%) Wilson disease patients. </p><p>Kusuda et al. (2000) described the R788L mutation in compound heterozygous state with an in-frame deletion, 3892delGTC (606882.0011), in a Japanese patient. Likewise, they commented on the high frequency of this mutation in Asians and stated that it has not been reported in Caucasian patients. </p><p>Wu et al. (2001) reported the frequency of the R788L mutation in Chinese patients to be 37.7%, which represented the most common mutation found in 84 patients with Wilson disease. The authors also found that homozygosity for the mutation was associated with a significantly earlier age of disease onset, lower levels of ceruloplasmin, and hepatic symptoms at presentation as compared to heterozygosity. </p><p>Gu et al. (2003) likewise found the R778L mutation in 55% of Chinese Han and Hui patients in at least 1 allele. </p><p>Park et al. (2007) found that the R778L mutation had an allele frequency of 39.2% among 120 unrelated Korean patients with Wilson disease. </p><p>Park et al. (2009) found heterozygosity for the R778L allele in 6 of 500 healthy Korean individuals, yielding a carrier frequency of 0.6% in this population. </p><p>Wang et al. (2011) found that the R778L mutation was the most common mutation among 69 Chinese patients with Wilson disease, accounting for 23.29% of mutant alleles. </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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|
<div>
|
|
<h4>
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<span class="mim-font">
|
|
<strong>.0010 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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ATP7B, 15-BP DEL, NT-441
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|
<br />
|
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|
|
SNP: rs1484840087,
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|
|
|
|
|
ClinVar: RCV000671857
|
|
|
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|
|
</span>
|
|
</div>
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|
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<div>
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<span class="mim-text-font">
|
|
<p>Loudianos et al. (1999) characterized the putative promoter and 5-prime untranslated region of the WND gene and carried out mutation analysis in this region in Sardinian patients with Wilson disease (WND; 277900) with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion from position -441 to position -427, 5-prime to the translation start site within the 5-prime UTR in all chromosomes with this common haplotype. Expression assays demonstrated a 75% reduction in the transcriptional activity of the mutated sequence compared to that of the normal sequence. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. </p><p>Cullen et al. (2003) examined genetic variation in the promoter and 5-prime UTR of the ATP7B gene in patients with Wilson disease. Three of 37 patients were heterozygous for the 15-bp deletion between nucleotides -424 and -441. In addition, 2 novel single-nucleotide changes were identified within the 5-prime UTR and promoter of ATP7B, but these were found at a similar frequency in control chromosomes and were apparently normal variants. The results suggested that mutations in regulatory elements of ATP7B are uncommon in patients of European ancestry, except in Sardinia. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
ATP7B, 3-BP DEL, 3892GTC
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|
<br />
|
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|
|
SNP: rs2138570625,
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|
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|
|
|
|
ClinVar: RCV000004058
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with Wilson disease (WND; 277900), Kusuda et al. (2000) found compound heterozygosity for an in-frame GTC deletion (3892delGTC), predicted to remove a valine residue, and the frequent Asian mutation R778L (606882.0009), which apparently has not been observed in Caucasians. </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>.0012 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ASP765ASN
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|
<br />
|
|
|
|
SNP: rs28942075,
|
|
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|
|
|
gnomAD: rs28942075,
|
|
|
|
|
|
ClinVar: RCV000004059
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with Wilson disease (WND; 277900), Figus et al. (1995) identified a GAC-to-AAC change in the ATP7B gene, resulting in an asp765-to-asn substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, GLY943SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28942076,
|
|
|
|
|
|
gnomAD: rs28942076,
|
|
|
|
|
|
ClinVar: RCV000004060, RCV001091638
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with Wilson disease (WND; 277900), Thomas et al. (1995) identified a GGT-to-AGT change in the ATP7B gene, resulting in a gly943-to-ser mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ARG919GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907993,
|
|
|
|
|
|
gnomAD: rs121907993,
|
|
|
|
|
|
ClinVar: RCV000004061, RCV001818123, RCV004678595
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs with disparate clinical phenotypes of Wilson disease (WND; 277900), Takeshita et al. (2002) found compound heterozygosity for 2 ATP7B mutations: R778L (606882.0009) and R919G. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, 1-BP DEL, 2511A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs777362050,
|
|
|
|
|
|
gnomAD: rs777362050,
|
|
|
|
|
|
ClinVar: RCV000169035
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 2 sibs had disparate Wilson disease (WND; 277900) phenotypes, Takeshita et al. (2002) found that each had compound heterozygosity for 2 ATP7B mutations: 2511delA and A874V (606882.0016). In this family, the second male child showed neurologic symptoms at 32 years of age and was found to have the hepatoneurologic type of Wilson disease; on subsequent family screening, the 35-year-old first female sib was found to have the hepatic form. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ALA874VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907994,
|
|
|
|
|
|
gnomAD: rs121907994,
|
|
|
|
|
|
ClinVar: RCV000004055, RCV001091639
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ala874-to-val (A874V) mutation in the ATP7B gene that was found in compound heterozygous state in 2 sibs with Wilson disease (WND; 277900) by Takeshita et al. (2002), see 606882.0015. </p><p>Park et al. (2009) found heterozygosity for the A874V allele in 2 of 500 healthy Korean individuals, yielding a carrier frequency of 0.2% in this population. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ASN1270SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907990,
|
|
|
|
|
|
gnomAD: rs121907990,
|
|
|
|
|
|
ClinVar: RCV000004063, RCV000196058, RCV000504595, RCV000595271, RCV002354147, RCV003904803
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Thomas et al. (1995) identified an asn1270-to-ser (N1270S) mutation, which they referred to as asn1271-to-ser (N1271S), in the ATP7B gene in an Italian patient with Wilson disease (WND; 277900). This mutation was found to account for 61% of all mutations in Costa Rican patients and 4.9% in Japanese patients (Okada et al., 2000; Shah et al., 1997). Yoo (2002) found this mutation in 12.1% of Korean patients with Wilson disease. In most cases it was found in compound heterozygosity with the R778L mutation (606882.0009). </p><p>Park et al. (2009) found heterozygosity for the N1270S allele in 2 of 500 healthy Korean individuals, yielding a carrier frequency of 0.2% in this population. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ARG969GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907996,
|
|
|
|
|
|
gnomAD: rs121907996,
|
|
|
|
|
|
ClinVar: RCV000004064, RCV000270891, RCV003904804
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with Wilson disease (WND; 277900), Figus et al. (1995) identified a 2906G-A transition in exon 13 of the ATP7B gene, resulting in an arg969-to-gln (R969Q) substitution. Panagiotakaki et al. (2004) found this mutation in 12% of chromosomes from 93 Greek patients with Wilson disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, THR766ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907997,
|
|
|
|
|
|
gnomAD: rs121907997,
|
|
|
|
|
|
ClinVar: RCV000004065
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wilson disease (WND; 277900), Pendlebury et al. (2004) identified a homozygous thr766-to-arg (T766R) substitution in the ATP7B gene within transmembrane domain 4 of the protein. The case was unusual in that the patient presented with sudden onset of slurred speech, dysphagia, and difficulty walking. A preliminary diagnosis of ischemic stroke was made, but a more detailed work-up suggested Wilson disease. Both parents were heterozygous for the mutation and originated from the same small village in central England. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, MET645ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907998,
|
|
|
|
|
|
gnomAD: rs121907998,
|
|
|
|
|
|
ClinVar: RCV000004066, RCV001508347, RCV002408449, RCV003398442
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 22 of 40 (55%) unrelated Spanish patients with Wilson disease (WND; 277900), Margarit et al. (2005) identified a met645-to-arg (M645R) substitution in exon 6 of the ATP7B gene, between the sixth copper-binding domain and the first transmembrane region. The patients were all compound heterozygotes for mutation in the ATP7B gene, and all had the hepatic form of the disease. In 6 patients in whom M645R was combined with a nonsense mutation, there was early onset of the disease, occurring between 5 and 14 years of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, ILE1148THR AND GLY1176ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853279, rs60431989,
|
|
|
|
|
|
gnomAD: rs60431989,
|
|
|
|
|
|
ClinVar: RCV000004067, RCV000023582, RCV000727509, RCV001852911, RCV002453275
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wilson disease (WND; 277900) from a small village in Crete with an unusually high frequency of the disorder, Dedoussis et al. (2005) identified compound heterozygosity involving 3 different mutations in the ATP7B gene. An ile1148-to-thr substitution (I1148T) and a gly1176-to-arg substitution (G1176R) cosegregated in cis in the same patient. The other allele of this patient carried a nonsense mutation (Q289X; 606882.0022). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 WILSON DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ATP7B, GLN289TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907999,
|
|
|
|
|
|
gnomAD: rs121907999,
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ClinVar: RCV000004068, RCV000421016
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the gln289-to-ter (Q289X) mutation in the ATP7B gene that was found in compound heterozygous state in a patient with Wilson disease (WND; 277900) by Dedoussis et al. (2005), see 606882.0021. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0023 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, LEU708PRO
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<br />
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SNP: rs121908000,
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gnomAD: rs121908000,
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ClinVar: RCV000004069, RCV000507833, RCV000597397
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 18 individuals with Wilson disease (WND; 277900) from the Canary Islands of Spain, Garcia-Villarreal et al. (2000) identified a T-to-C transition in exon 8 of the ATP7B gene, resulting in a leu708-to-pro (L708P) substitution. Twelve patients were homozygous for the mutation. Homozygous patients tended to have a neurologic presentation at an average age of 16 years. Haplotype analysis indicated a founder effect. The L708P mutation was estimated to have arisen in Gran Canaria over 56 generations ago, in pre-Hispanic times. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0024 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, GLY691ARG
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<br />
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SNP: rs121908001,
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ClinVar: RCV000004070
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 5 affected members of a consanguineous Lebanese family with Wilson disease (WND; 277900), Barada et al. (2007) identified a homozygous G-to-A transition in exon 7 of the ATP7B gene, resulting in a gly691-to-arg (G691R) substitution in the TM2 domain. Four SNPs in the ATP7B gene were also inherited homozygously with the G691R substitution and may have contributed to altered protein function. Two patients presented at ages 7 and 9 years, respectively, with advanced hepatic cirrhosis. The 3 other affected individuals, who were asymptomatic, were detected by screening before age 14. Four additional family members, 3 of whom were deceased, were reportedly affected. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0025 WILSON DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ATP7B, ILE1148THR
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<br />
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ClinVar: RCV000004067, RCV000023582, RCV000727509, RCV002453275
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In Chinese patients with Wilson disease (WND; 277900), Wang et al. (2011) identified a 3443T-C transition in exon 16 of the ATP7B gene, resulting in an ile1148-to-thr (I1148T) substitution in the ATP loop of the protein. The I1148T mutation was the second most common mutation among 69 Chinese patients with Wilson disease, accounting for 9.59% of mutant alleles. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Barada, K., Nemer, G., ElHajj, I. I., Touma, J., Cortas, N., Boustany, R.-M., Usta, J.
|
|
<strong>Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease. (Letter)</strong>
|
|
Clin. Genet. 72: 264-267, 2007.
|
|
|
|
|
|
[PubMed: 17718866]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00853.x]
|
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|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W.
|
|
<strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong>
|
|
Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
|
|
|
|
|
|
[PubMed: 8298639]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1293-327]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cullen, L. M., Prat, L., Cox, D. W.
|
|
<strong>Genetic variation in the promoter and 5-prime UTR of the copper transporter, ATP7B, in patients with Wilson disease.</strong>
|
|
Clin. Genet. 64: 429-432, 2003.
|
|
|
|
|
|
[PubMed: 14616767]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00160.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dedoussis, G. V. Z., Genschel, J., Sialvera, T.-E., Bochow, B., Manolaki, N., Manios, Y., Tsafantakis, E., Schmidt, H.
|
|
<strong>Wilson disease: high prevalence in a mountaineous (sic) area of Crete.</strong>
|
|
Ann. Hum. Genet. 69: 268-274, 2005.
|
|
|
|
|
|
[PubMed: 15845031]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1529-8817.2005.00171.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dijkstra, M., In't Veld, G., van den Berg, G. J., Muller, M., Kuipers, F., Vonk, R. J.
|
|
<strong>Adenosine triphosphate-dependent copper transport in isolated rat liver plasma membranes.</strong>
|
|
J. Clin. Invest. 95: 412-416, 1995.
|
|
|
|
|
|
[PubMed: 7814642]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI117670]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duc, H.-H., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G.
|
|
<strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong>
|
|
Europ. J. Hum. Genet. 6: 616-623, 1998.
|
|
|
|
|
|
[PubMed: 9887381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200237]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others.
|
|
<strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong>
|
|
Am. J. Hum. Genet. 57: 1318-1324, 1995.
|
|
|
|
|
|
[PubMed: 8533760]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Firneisz, G., Lakatos, P. L., Szalay, F., Polli, C., Glant, T. T., Ferenci, P.
|
|
<strong>Common mutations of ATP7B in Wilson disease patients from Hungary.</strong>
|
|
Am. J. Med. Genet. 108: 23-28, 2002.
|
|
|
|
|
|
[PubMed: 11857545]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10220]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Forbes, J. R., Cox, D. W.
|
|
<strong>Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.</strong>
|
|
Hum. Molec. Genet. 9: 1927-1935, 2000.
|
|
|
|
|
|
[PubMed: 10942420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.13.1927]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A.
|
|
<strong>High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.</strong>
|
|
Hepatology 32: 1329-1336, 2000.
|
|
|
|
|
|
[PubMed: 11093740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1053/jhep.2000.20152]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gourdon, P., Liu, X.-Y., Skjorringe, T., Morth, J. P., Moller, L. B., Pedersen, B. P., Nissen, P.
|
|
<strong>Crystal structure of a copper-transporting PIB-type ATPase.</strong>
|
|
Nature 475: 59-64, 2011.
|
|
|
|
|
|
[PubMed: 21716286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10191]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A.
|
|
<strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.</strong>
|
|
Clin. Genet. 68: 524-532, 2005.
|
|
|
|
|
|
[PubMed: 16283883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00528.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gu, Y.-H., Kodama, H., Du, S.-L., Gu, Q.-J., Sun, H.-J., Ushijima, H.
|
|
<strong>Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.</strong>
|
|
Clin. Genet. 64: 479-484, 2003.
|
|
|
|
|
|
[PubMed: 14986826]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1399-0004.2003.00179.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K.
|
|
<strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong>
|
|
Hum. Genet. 118: 49-57, 2005.
|
|
|
|
|
|
[PubMed: 16133174]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-005-0007-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harris, E. D.
|
|
<strong>Cellular copper transport and metabolism.</strong>
|
|
Annu. Rev. Nutr. 20: 291-310, 2000.
|
|
|
|
|
|
[PubMed: 10940336]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.nutr.20.1.291]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Houwen, R. H. J., Juyn, J., Hoogenraad, T. U., Ploos van Amstel, J. K., Berger, R.
|
|
<strong>H714Q mutation in Wilson disease is associated with late, neurological presentation.</strong>
|
|
J. Med. Genet. 32: 480-482, 1995.
|
|
|
|
|
|
[PubMed: 7666402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.6.480]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H.
|
|
<strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong>
|
|
Hum. Mutat. 11: 275-278, 1998.
|
|
|
|
|
|
[PubMed: 9554743]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<275::AID-HUMU4>3.0.CO;2-L]
|
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|
|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kusuda, Y., Hamaguchi, K., Mori, T., Shin, R., Seike, M., Sakata, T.
|
|
<strong>Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.</strong>
|
|
J. Hum. Genet. 45: 86-91, 2000.
|
|
|
|
|
|
[PubMed: 10721669]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100380050017]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
La Fontaine, S., Theophilos, M. B., Firth, S. D., Gould, R., Parton, R. G., Mercer, J. F. B.
|
|
<strong>Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase.</strong>
|
|
Hum. Molec. Genet. 10: 361-370, 2001.
|
|
|
|
|
|
[PubMed: 11157799]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/10.4.361]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Lim, C. M., Cater, M. A., Mercer, J. F. B., La Fontaine, S.
|
|
<strong>Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A.</strong>
|
|
J. Biol. Chem. 281: 14006-14014, 2006.
|
|
|
|
|
|
[PubMed: 16554302]
|
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|
|
[Full Text: https://doi.org/10.1074/jbc.M512745200]
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</p>
|
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A.
|
|
<strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong>
|
|
Hum. Mutat. 14: 294-303, 1999.
|
|
|
|
|
|
[PubMed: 10502776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<294::AID-HUMU4>3.0.CO;2-9]
|
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M.
|
|
<strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong>
|
|
Hum. Mutat. 12: 89-94, 1998.
|
|
|
|
|
|
[PubMed: 9671269]
|
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|
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|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)12:2<89::AID-HUMU3>3.0.CO;2-G]
|
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Loudianos, G., Lovicu, M., Dessi, V., Tzetis, M., Kanavakis, E., Zancan, L., Zelante, L., Galvez-Galvez, C., Cao, A.
|
|
<strong>Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B.</strong>
|
|
Hum. Mutat. 20: 260-266, 2002.
|
|
|
|
|
|
[PubMed: 12325021]
|
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|
|
[Full Text: https://doi.org/10.1002/humu.10121]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Loudianos, G., Lovicu, M., Solinas, P., Kanavakis, E., Tzetis, M., Manolaki, N., Panagiotakaki, E., Karpathios, T., Cao, A.
|
|
<strong>Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.</strong>
|
|
Genet. Test. 4: 399-402, 2000.
|
|
|
|
|
|
[PubMed: 11216666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1089/109065700750065162]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luoma, L. M., Deeb, T. M., Macintyre, G., Cox, D. W.
|
|
<strong>Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.</strong>
|
|
Hum. Mutat. 31: 569-577, 2010.
|
|
|
|
|
|
[PubMed: 20333758]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.21228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F.
|
|
<strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong>
|
|
Clin. Genet. 68: 61-68, 2005.
|
|
|
|
|
|
[PubMed: 15952988]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00439.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H.
|
|
<strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.</strong>
|
|
Hum. Mutat. 15: 454-462, 2000.
|
|
|
|
|
|
[PubMed: 10790207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<454::AID-HUMU7>3.0.CO;2-J]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Panagiotakaki, E., Tzetis, M., Manolaki, N., Loudianos, G., Papatheodorou, A., Manesis, E., Nousia-Arvanitakis, S., Syriopoulou, V., Kanavakis, E.
|
|
<strong>Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).</strong>
|
|
Am. J. Med. Genet. 131A: 168-173, 2004. Note: Erratum: Personal Communication Kanavakis: Athens, Greece 1/24/2005.
|
|
|
|
|
|
[PubMed: 15523622]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30345]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W.
|
|
<strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong>
|
|
Clin. Genet. 75: 405-407, 2009.
|
|
|
|
|
|
[PubMed: 19419418]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01132.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W.
|
|
<strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong>
|
|
Hum. Mutat. 28: 1108-1113, 2007.
|
|
|
|
|
|
[PubMed: 17587212]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20574]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Payne, A. S., Kelly, E. J., Gitlin, J. D.
|
|
<strong>Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 10854-10859, 1998.
|
|
|
|
|
|
[PubMed: 9724794]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.95.18.10854]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pendlebury, S. T., Rothwell, P. M., Dalton, A., Burton, E. A.
|
|
<strong>Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation.</strong>
|
|
Neurology 63: 1982-1983, 2004.
|
|
|
|
|
|
[PubMed: 15557537]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000144192.30426.38]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petrukhin, K. E., Lutsenko, S., Chernov, I., Ross, B. M., Kaplan, J. H., Gilliam, T. C.
|
|
<strong>Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions.</strong>
|
|
Hum. Molec. Genet. 3: 1647-1656, 1994.
|
|
|
|
|
|
[PubMed: 7833924]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.9.1647]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reed, V., Williamson, P., Bull, P. C., Cox, D. W., Boyd, Y.
|
|
<strong>Mapping of the mouse homologue of the Wilson disease gene to mouse chromosome 8.</strong>
|
|
Genomics 28: 573-575, 1995.
|
|
|
|
|
|
[PubMed: 7490097]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.1191]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N.
|
|
<strong>The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 202: 512-518, 1994.
|
|
|
|
|
|
[PubMed: 8037756]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1994.1958]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shah, A. B., Chernov, I., Zhang, H. T., Ross, B. M., Das, K., Lutsenko, S., Parano, E., Pavone, L., Evgrafov, O., Ivanova-Smolenskaya, I. A., Anneren, G., Westermark, K., Urrutia, F. H., Penchaszadeh, G. K., Sternlieb, I., Scheinberg, I. H., Gilliam, T. C., Petrukhin, K.
|
|
<strong>Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation and functional analyses.</strong>
|
|
Am. J. Hum. Genet. 61: 317-328, 1997.
|
|
|
|
|
|
[PubMed: 9311736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/514864]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T.
|
|
<strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong>
|
|
J. Hum. Genet. 47: 543-547, 2002.
|
|
|
|
|
|
[PubMed: 12376745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100380200082]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C.
|
|
<strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong>
|
|
Nature Genet. 5: 344-350, 1993.
|
|
|
|
|
|
[PubMed: 8298641]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1293-344]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T.
|
|
<strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong>
|
|
J. Biol. Chem. 273: 1815-1820, 1998.
|
|
|
|
|
|
[PubMed: 9430732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.273.3.1815]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
|
|
<strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong>
|
|
Nature Genet. 9: 210-217, 1995. Note: Erratum: Nature Genet. 9: 451 only, 1995.
|
|
|
|
|
|
[PubMed: 7626145]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0295-210]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W.
|
|
<strong>Wilson disease in Iceland: a clinical and genetic study.</strong>
|
|
Am. J. Hum. Genet. 56: 1140-1146, 1995.
|
|
|
|
|
|
[PubMed: 7726170]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
|
|
<strong>Haplotypes and mutations in Wilson disease.</strong>
|
|
Am. J. Hum. Genet. 56: 1315-1319, 1995.
|
|
|
|
|
|
[PubMed: 7762553]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Todorov, T., Savov, A., Jelev, H., Panteleeva, E., Konstantinova, D., Krustev, Z., Mihaylova, V., Tournev, I., Tankova, L., Tzolova, N., Kremensky, I.
|
|
<strong>Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. (Letter)</strong>
|
|
Clin. Genet. 68: 474-476, 2005.
|
|
|
|
|
|
[PubMed: 16207219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00516.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. F., Dooley, J. S.
|
|
<strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong>
|
|
Hum. Genet. 139: 1065-1075, 2020.
|
|
|
|
|
|
[PubMed: 32248359]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-020-02161-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M.
|
|
<strong>Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.</strong>
|
|
J. Hum. Genet. 56: 660-665, 2011.
|
|
|
|
|
|
[PubMed: 21796144]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/jhg.2011.76]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilson, D. C., Phillips, M. J., Cox, D. W., Roberts, E. A.
|
|
<strong>Severe hepatic Wilson's disease in preschool-aged children.</strong>
|
|
J. Pediat. 137: 719-722, 2000.
|
|
|
|
|
|
[PubMed: 11060541]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1067/mpd.2000.108569]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, Z.-Y., Wang, N., Lin, M.-T., Fang, L., Murong, S.-X., Yu, L.
|
|
<strong>Mutation analysis and the correlation between genotype and phenotype of arg778leu mutation in Chinese patients with Wilson disease.</strong>
|
|
Arch. Neurol. 58: 971-976, 2001.
|
|
|
|
|
|
[PubMed: 11405812]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.58.6.971]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, X.-L., Miura, N., Kawarada, Y., Terada, K., Petrukhin, K., Gilliam, T. C., Sugiyama, T.
|
|
<strong>Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.</strong>
|
|
Biochem. J. 326: 897-902, 1997.
|
|
|
|
|
|
[PubMed: 9307043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bj3260897]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoo, H. W.
|
|
<strong>Identification of novel mutations and the 3 most common mutations in the human ATP7B gene of Korean patients with Wilson disease.</strong>
|
|
Genet. Med. 4: 43S-48S, 2002.
|
|
|
|
|
|
[PubMed: 12544487]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-200211001-00009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 02/03/2021<br>Patricia A. Hartz - updated : 8/9/2012<br>Cassandra L. Kniffin - updated : 11/1/2011<br>Ada Hamosh - updated : 9/6/2011<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 8/30/2010<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Cassandra L. Kniffin - updated : 10/26/2007<br>Cassandra L. Kniffin - updated : 3/21/2007<br>Marla J. F. O'Neill - updated : 10/25/2006<br>Marla J. F. O'Neill - updated : 12/28/2005<br>Cassandra L. Kniffin - updated : 12/9/2005<br>Patricia A. Hartz - updated : 11/10/2005<br>Victor A. McKusick - updated : 8/19/2005<br>Marla J. F. O'Neill - updated : 7/5/2005<br>Cassandra L. Kniffin - updated : 3/15/2005<br>Victor A. McKusick - updated : 1/14/2005<br>Victor A. McKusick - updated : 1/12/2004<br>Victor A. McKusick - updated : 12/4/2003<br>Ada Hamosh - updated : 3/4/2003<br>Victor A. McKusick - updated : 1/7/2003<br>Victor A. McKusick - updated : 11/1/2002<br>Cassandra L. Kniffin - updated : 9/6/2002
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Cassandra L. Kniffin : 4/25/2002
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carol : 04/28/2022<br>carol : 02/04/2021<br>carol : 02/03/2021<br>carol : 03/26/2020<br>carol : 03/25/2020<br>carol : 10/18/2016<br>carol : 05/04/2015<br>mcolton : 5/4/2015<br>carol : 12/19/2013<br>terry : 11/6/2012<br>mgross : 8/10/2012<br>terry : 8/9/2012<br>carol : 8/8/2012<br>carol : 11/1/2011<br>ckniffin : 11/1/2011<br>alopez : 9/7/2011<br>terry : 9/6/2011<br>carol : 8/5/2011<br>wwang : 12/29/2010<br>ckniffin : 12/3/2010<br>wwang : 9/3/2010<br>ckniffin : 8/30/2010<br>wwang : 11/14/2008<br>mgross : 3/10/2008<br>wwang : 12/14/2007<br>ckniffin : 11/14/2007<br>wwang : 11/6/2007<br>ckniffin : 10/26/2007<br>wwang : 4/4/2007<br>ckniffin : 3/21/2007<br>wwang : 11/7/2006<br>wwang : 10/26/2006<br>terry : 10/25/2006<br>wwang : 1/5/2006<br>terry : 12/28/2005<br>wwang : 12/9/2005<br>ckniffin : 12/7/2005<br>mgross : 11/16/2005<br>terry : 11/10/2005<br>wwang : 9/1/2005<br>wwang : 8/25/2005<br>terry : 8/19/2005<br>wwang : 7/11/2005<br>wwang : 7/11/2005<br>terry : 7/5/2005<br>ckniffin : 3/15/2005<br>wwang : 1/27/2005<br>wwang : 1/25/2005<br>alopez : 1/25/2005<br>wwang : 1/20/2005<br>terry : 1/14/2005<br>carol : 1/20/2004<br>terry : 1/12/2004<br>alopez : 12/10/2003<br>terry : 12/4/2003<br>cwells : 3/4/2003<br>cwells : 3/4/2003<br>cwells : 1/8/2003<br>tkritzer : 1/7/2003<br>tkritzer : 11/4/2002<br>terry : 11/1/2002<br>carol : 9/10/2002<br>ckniffin : 9/6/2002<br>terry : 5/20/2002<br>ckniffin : 4/29/2002<br>carol : 4/29/2002<br>ckniffin : 4/29/2002
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