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<title>
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Entry
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- *300808 - G PROTEIN-COUPLED RECEPTOR 143; GPR143
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- OMIM
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</ul>
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</div>
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</nav>
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</div>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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</form>
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<p />
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<div id="mimAlertBanner">
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300808</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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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>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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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="#geneStructure">Gene Structure</a>
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</li>
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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>
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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>
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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="#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/300808">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>
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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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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000101850;t=ENST00000467482" 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=4935" 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=300808" 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=ENSG00000101850;t=ENST00000467482" 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_000273,XM_005274541,XM_024452388" 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_000273" 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=300808" 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=02355&isoform_id=02355_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/GPR143" 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/1113125,3219999,46362561,119619179,270265839,530421154,1370516269,1746153618,1746153620,1746153622,1746153624,1746153626,1746153628,1746153630,1746153632,1746153634,1746153636,1746153638,2462629612,2462629614" 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/P51810" 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=4935" 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=ENSG00000101850;t=ENST00000467482" 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=GPR143" 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=GPR143" 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+4935" 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/GPR143" 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:4935" 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/4935" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chrX&hgg_gene=ENST00000467482.6&hgg_start=9725346&hgg_end=9778602&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">
|
|
<span class="panel-title">
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<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:20145" 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/gpr143" 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=300808[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=300808[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/GPR143/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/ENSG00000101850" 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=GPR143" 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=GPR143" 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=GPR143" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GPR143&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/PA31872" 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:20145" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:107193" 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/GPR143#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:107193" 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/4935/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4935" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1476" 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">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<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://reactome.org/content/query?q=GPR143&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> 78642008<br />
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<strong>ICD10CM:</strong> E70.310<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>
|
|
300808
|
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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>
|
|
<span class="mim-font">
|
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G PROTEIN-COUPLED RECEPTOR 143; GPR143
|
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
OA1 GENE
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GPR143" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GPR143</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/50?start=-3&limit=10&highlight=50">Xp22.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:9725346-9778602&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">X:9,725,346-9,778,602</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300814,300500" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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<p>GPR143 is a G protein-coupled receptor (GPCR) that is exclusively expressed by melanocytes and retinal pigment epithelium (RPE). Unlike other GPCRs, GPR143 is not localized to the cell surface, but is exclusively found on the membranes of intracellular organelles, namely late endosomes/lysosomes and melanosomes (summary by <a href="#13" class="mim-tip-reference" title="Palmisano, I., Bagnato, P., Palmigiano, A., Innamorati, G., Rotondo, G., Altimare, D., Venturi, C., Sviderskaya, E. V., Piccirillo, R., Coppola, M., Marigo, V., Incerti, B., Ballabio, A., Surace, E. M., Tacchetti, C., Bennett, D. C., Schiaffino, M. V. <strong>The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells.</strong> Hum. Molec. Genet. 17: 3487-3501, 2008. Note: Erratum: Hum. Molec. Genet. 26: 3028-3029, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18697795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18697795</a>] [<a href="https://doi.org/10.1093/hmg/ddn241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18697795">Palmisano et al. (2008)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18697795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By hybridization of the ocular albinism type I (OA1; <a href="/entry/300500">300500</a>) critical region in 4 patients to a human retina cDNA library, followed by RACE-PCR analysis, <a href="#1" class="mim-tip-reference" title="Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A. <strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong> Nature Genet. 10: 13-19, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647783</a>] [<a href="https://doi.org/10.1038/ng0595-13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647783">Bassi et al. (1995)</a> cloned GPR143. RT-PCR analysis detected a 1.6-kb transcript that was expressed at high levels in RNA samples from retina, including RPE, and from melanoma, with weak expression in brain and adrenal gland. The deduced 424-amino acid GPR143 protein has at least 6 putative transmembrane domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Newton, J. M., Orlow, S. J., Barsh, G. S. <strong>Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene.</strong> Genomics 37: 219-225, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921399</a>] [<a href="https://doi.org/10.1006/geno.1996.0545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921399">Newton et al. (1996)</a> cloned and characterized mouse Gpr143, which they referred to as Moa1. Two Moa1 variants were isolated from a melanoma cDNA library and predicted proteins of 405 and 249 amino acids with 6 and 2 transmembrane-spanning regions, respectively. In adult tissues, both Moa1 isoforms were detected in the eye by Northern hybridization. In neonatal tissues, Moa1 RNA was detected in both skin and eye by Northern hybridization and was not affected by the absence of pigment in mice carrying the 'albino' mutation or by the type of pigment synthesized, i.e., eumelanin or pheomelanin, in mice carrying the 'black-and-tan' mutation. Expression of Moa1 RNA was not detected in embryonic tissues by Northern analysis or by in situ hybridization despite the active synthesis of ocular pigment by embryonic stage E16.5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8921399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunogold electron microscopy of human melanocytic cell line MNT-1, <a href="#5" class="mim-tip-reference" title="Giordano, F., Bonetti, C., Surace, E. M., Marigo, V., Raposo, G. <strong>The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.</strong> Hum. Molec. Genet. 18: 4530-4545, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19717472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19717472</a>] [<a href="https://doi.org/10.1093/hmg/ddp415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19717472">Giordano et al. (2009)</a> showed that GPR143 was widely distributed throughout the endo-melanosomal system but that most of the endogenous protein was localized in unpigmented stage II melanosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19717472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#17" class="mim-tip-reference" title="Schiaffino, M. V., Bassi, M. T., Galli, L., Renieri, A., Bruttini, M., De Nigris, F., Bergen, A. A. B., Charles, S. J., Yates, J. R. W., Meindl, A., Lewis, R. A., King, R. A., Ballabio, A. <strong>Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.</strong> Hum. Molec. Genet. 4: 2319-2325, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634705</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634705">Schiaffino et al. (1995)</a> determined that the GPR143 gene contains 9 exons and spans 40 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634705" 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="Vetrini, F., Auricchio, A., Du, J., Angeletti, B., Fisher, D. E., Ballabio, A., Marigo, V. <strong>The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis.</strong> Molec. Cell. Biol. 24: 6550-6559, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15254223[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.15.6550-6559.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15254223">Vetrini et al. (2004)</a> identified several putative transcription factor-binding sites in the 5-prime proximal region of the OA1 promoter, including sites for SP1 (<a href="/entry/189906">189906</a>), GBX2 (<a href="/entry/601135">601135</a>), HES1 (<a href="/entry/139605">139605</a>), and MITF (<a href="/entry/156845">156845</a>). There is no TATA box. The mouse Oa1 promoter region shows a nearly identical organization. Using several in vitro and in vivo approaches, <a href="#21" class="mim-tip-reference" title="Vetrini, F., Auricchio, A., Du, J., Angeletti, B., Fisher, D. E., Ballabio, A., Marigo, V. <strong>The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis.</strong> Molec. Cell. Biol. 24: 6550-6559, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15254223[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.15.6550-6559.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15254223">Vetrini et al. (2004)</a> confirmed that the MITF site, an E-box at position -28 from the transcription start site, was bound by the MITF-M isoform and was functional in pigmented mouse and human cells. MITF-M could drive expression of OA1 in melanocytes and retinal pigment epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15254223" 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="#1" class="mim-tip-reference" title="Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A. <strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong> Nature Genet. 10: 13-19, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647783</a>] [<a href="https://doi.org/10.1038/ng0595-13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647783">Bassi et al. (1995)</a> mapped the GPR143 gene to chromosome Xp22.3-p22.2, approximately 20 kb on the telomeric side of the APXL gene (SHROOM2; <a href="/entry/300103">300103</a>). APXL spans 80 of the 110 kb of the OA1 critical region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647783" 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>Comparative mapping of the X chromosome in eutherian mammals has revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. <a href="#4" class="mim-tip-reference" title="Dinulos, M. B., Bassi, M. T., Rugarli, E. I., Chapman, V., Ballabio, A., Disteche, C. M. <strong>A new region of conservation is defined between human and mouse X chromosomes.</strong> Genomics 35: 244-247, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661129</a>] [<a href="https://doi.org/10.1006/geno.1996.0347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661129">Dinulos et al. (1996)</a> mapped the murine homologs of OA1 and APXL. They found that the 2 genes map to bands F2-F3 in both M. spretus and the laboratory strains C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661129" 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>Interspecific backcross mapping by <a href="#11" class="mim-tip-reference" title="Newton, J. M., Orlow, S. J., Barsh, G. S. <strong>Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene.</strong> Genomics 37: 219-225, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921399</a>] [<a href="https://doi.org/10.1006/geno.1996.0545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921399">Newton et al. (1996)</a> yielded a map order and distances (in cM) of cen-Moa1-3.1 +/- 1.8-Piga (<a href="/entry/311770">311770</a>)-2.1 +/- 1.5-Amel (AMELX; <a href="/entry/300391">300391</a>), indicating that Moa1 is located much farther away from the pseudoautosomal region than its human homolog. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8921399" 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>GPCRs participate in the most common signal transduction system at the plasma membrane. The wide distribution of heterotrimeric G proteins in the internal membranes suggests that a similar signaling mechanism might also be used at intracellular locations. <a href="#18" class="mim-tip-reference" title="Schiaffino, M. V., d'Addio, M., Alloni, A., Baschirotto, C., Valetti, C., Cortese, K., Puri, C., Bassi, M. T., Colla, C., De Luca, M., Tacchetti, C., Ballabio, A. <strong>Ocular albinism: evidence for a defect in an intracellular signal transduction system.</strong> Nature Genet. 23: 108-112, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471510</a>] [<a href="https://doi.org/10.1038/12715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471510">Schiaffino et al. (1999)</a> provided structural evidence that the protein product of the OA1 gene, a pigment cell-specific integral membrane glycoprotein, represents a novel member of the GPCR superfamily and demonstrated that it binds heterotrimeric G proteins. Moreover, they showed that OA1 is not found at the plasma membrane, being instead targeted to specialized intracellular organelles, the melanosomes. The data suggested that OA1 represents the first example of an exclusively intracellular GPCR and supported the hypothesis that GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Giordano, F., Bonetti, C., Surace, E. M., Marigo, V., Raposo, G. <strong>The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.</strong> Hum. Molec. Genet. 18: 4530-4545, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19717472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19717472</a>] [<a href="https://doi.org/10.1093/hmg/ddp415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19717472">Giordano et al. (2009)</a> used siRNA inactivation of GPR143 and combined morphologic and biochemical methods to investigate melanosome ultrastructure, melanosomal protein localization and expression in human pigmented melanocytic cells. GPR143 loss of function led to decreased pigmentation and caused formation of enlarged aberrant premelanosomes harboring disorganized fibrillar structures and displaying proteins of mature melanosomes and lysosomes at their membrane. GPR143 interacted biochemically with the premelanosomal protein MART1 (MLANA; <a href="/entry/605513">605513</a>). Inactivation of MART1 by siRNA led to decreased stability of GPR143 and was accompanied by similar defects in premelanosome biogenesis and composition. <a href="#5" class="mim-tip-reference" title="Giordano, F., Bonetti, C., Surace, E. M., Marigo, V., Raposo, G. <strong>The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.</strong> Hum. Molec. Genet. 18: 4530-4545, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19717472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19717472</a>] [<a href="https://doi.org/10.1093/hmg/ddp415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19717472">Giordano et al. (2009)</a> concluded that melanosome composition and identity are regulated at early stages by GPR143 and that MART1 likely acts as an escort protein for GPR143. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19717472" 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><strong><em>Ocular Albinism Type I</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A. <strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong> Nature Genet. 10: 13-19, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647783</a>] [<a href="https://doi.org/10.1038/ng0595-13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647783">Bassi et al. (1995)</a> identified 5 patients with OA1 (<a href="/entry/300500">300500</a>) who were carrying mutations within the GPR143 gene. Five intragenic deletions and a 2-bp insertion resulting in a premature stop codon (<a href="#0001">300808.0001</a>) were identified by DNA analysis of patients with OA1. Some of these deletions were not overlapping, making it highly unlikely that the mutation involved in OA1 is located in an intron of the gene. Fine molecular characterization of the gene in 1 patient demonstrated that the deletion removed part of a coding exon. The APXL gene was completely deleted in 1 patient with isolated OA1. However, an extensive search for point mutations was performed in the 4,848-bp coding region of APXL from 57 patients and no functionally relevant mutation was identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647783" 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="Schiaffino, M. V., Bassi, M. T., Galli, L., Renieri, A., Bruttini, M., De Nigris, F., Bergen, A. A. B., Charles, S. J., Yates, J. R. W., Meindl, A., Lewis, R. A., King, R. A., Ballabio, A. <strong>Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.</strong> Hum. Molec. Genet. 4: 2319-2325, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634705</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634705">Schiaffino et al. (1995)</a> screened the entire OA1 coding region and 5-prime and 3-prime sequences for mutations and detected mutations in only one-third (21 of 60) of their patients with OA, including 2 frameshifts (e.g., <a href="#0002">300808.0002</a>) and a splice site mutation leading to truncated OA1 proteins, a deletion of a threonine codon at position 290, and 4 missense mutations (e.g., <a href="#0008">300808.0008</a>), 2 of which involved amino acids located within putative transmembrane domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634705" 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="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> reported results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian OA probands, including 5 with additional, nonocular phenotypic abnormalities (<a href="#20" class="mim-tip-reference" title="Schnur, R. E., Wick, P. A., Bailey, C., Rebbeck, T., Weleber, R. G., Wagstaff, J., Grix, A. W., Pagon, R. A., Hockey, A., Edwards, M. J. <strong>Phenotypic variability in X-linked ocular albinism: relationship to linkage genotypes.</strong> Am. J. Hum. Genet. 55: 484-496, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7915878/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7915878</a>]" pmid="7915878">Schnur et al., 1994</a>). They detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2 to 8. They also identified 8 novel missense mutations that clustered within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. All told, 26 (approximately 90%) of 29 probands had detectable alterations in the OA1 gene, thus confirming that OA1 is the major locus for X-linked OA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7915878+9529334" 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 Denmark, <a href="#16" class="mim-tip-reference" title="Rosenberg, T., Schwartz, M. <strong>X-linked ocular albinism: prevalence and mutations--a national study.</strong> Europ. J. Hum. Genet. 6: 570-577, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887374</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887374">Rosenberg and Schwartz (1998)</a> performed a retrospective survey of 112 patients with ocular albinism identified in a national register, including 60 male patients with proven or presumed X-linked ocular albinism. Based on the birth year cohorts 1960 to 1989, a point prevalence for OA1 at birth of 1 in 60,000 live born was calculated. They identified 14 OA1 families in the Danish population and obtained DNA from affected persons in 9 families. Mutation analysis demonstrated 7 presumed pathogenic mutations in the 9 families: 5 single nucleotide substitutions predicting a change of conserved amino acids, including G35D (<a href="#0008">300808.0008</a>) and W133R (<a href="#0006">300808.0006</a>), when compared with the mouse OA1 homolog, 1 deletion leading to the skipping of exon 2, and 1 example of a single nucleotide substitution expected to affect the 5-prime splice site of intron 2 (<a href="#0007">300808.0007</a>). Subsequent genealogic investigations in the 3 families harboring the same mutation, W133R, disclosed that 2 of the 3 belonged to the same family. Clinical examination failed to identify any phenotype-genotype pattern except for the finding of a milder phenotype lacking iris translucency in the patient with the 5-prime splice site mutation of intron 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887374" 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="d'Addio, M., Pizzigoni, A., Bassi, M. T., Baschirotto, C., Valetti, C., Incerti, B., Clementi, M., De Luca, M., Ballabio, A., Schiaffino, M. V. <strong>Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.</strong> Hum. Molec. Genet. 9: 3011-3018, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11115845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11115845</a>] [<a href="https://doi.org/10.1093/hmg/9.20.3011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11115845">D'Addio et al. (2000)</a> characterized 19 independent missense mutations with respect to processing and subcellular distribution on expression in COS-7 cells. Eleven of the 19 OA1 mutants (approximately 60%) were retained in the endoplasmic reticulum, showing defective intracellular transport and glycosylation, consistent with protein misfolding. The remaining 8 OA1 mutants (approximately 40%) displayed sorting and processing behaviors indistinguishable from those of the wildtype protein. Most of the latter mutations clustered within the second and third cytosolic loops, 2 regions that in canonical GPCRs are known to be critical for their downstream signaling, including G protein coupling and effector activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11115845" 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="Oetting, W. S. <strong>New insights into ocular albinism type 1 (OA1): mutations and polymorphisms of the OA1 gene.</strong> Hum. Mutat. 19: 85-92, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793467</a>] [<a href="https://doi.org/10.1002/humu.10034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11793467">Oetting (2002)</a> found that a total of 25 missense, 2 nonsense, 9 frameshift, and 5 splicing mutations in the OA1 gene had been reported in association with type I ocular albinism. There were also reports of several deletions of some or all exons of the OA1 gene with deletions of exon 2 resulting from unequal crossing-over, due to flanking Alu repeats. <a href="#12" class="mim-tip-reference" title="Oetting, W. S. <strong>New insights into ocular albinism type 1 (OA1): mutations and polymorphisms of the OA1 gene.</strong> Hum. Mutat. 19: 85-92, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793467</a>] [<a href="https://doi.org/10.1002/humu.10034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11793467">Oetting (2002)</a> referred to an albinism database website. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11793467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Chinese patient with ocular albinism, <a href="#22" class="mim-tip-reference" title="Xiao, X., Zhang, Q. <strong>Iris hyperpigmentation in a Chinese family with ocular albinism and the GPR143 mutation.</strong> Am. J. Med. Genet. 149A: 1786-1788, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19610097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19610097</a>] [<a href="https://doi.org/10.1002/ajmg.a.32818" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19610097">Xiao and Zhang (2009)</a> identified an intragenic deletion in the GPR143 gene (<a href="#0013">300808.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19610097" 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>X-linked Congenital Nystagmus 6</em></strong></p><p>
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In a large 6-generation Chinese family with congenital nystagmus as the main feature (NYS6; <a href="/entry/300814">300814</a>), <a href="#10" class="mim-tip-reference" title="Liu, J. Y., Ren, X., Yang, X., Guo, T., Yao, Q., Li, L., Dai, X., Zhang, M., Wang, L., Liu, M., Wang, Q. K. <strong>Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation.</strong> J. Hum. Genet. 52: 565-570, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17516023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17516023</a>] [<a href="https://doi.org/10.1007/s10038-007-0152-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17516023">Liu et al. (2007)</a> analyzed 21 candidate genes and identified a missense mutation in the GPR143 gene (S89F; <a href="#0009">300808.0009</a>) in affected males and carrier females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17516023" 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="Zhou, P., Wang, Z., Zhang, J., Hu, L., Kong, X. <strong>Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus.</strong> Molec. Vis. 14: 1015-1019, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18523664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18523664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18523664[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="18523664">Zhou et al. (2008)</a> and <a href="#14" class="mim-tip-reference" title="Peng, Y., Meng, Y., Wang, Z., Qin, M., Li, X., Dian, Y., Huang, S. <strong>A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus.</strong> Molec. Vis. 15: 810-814, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19390656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19390656</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19390656[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19390656">Peng et al. (2009)</a> identified mutations in the GPR143 gene (<a href="#0011">300808.0011</a> and <a href="#0012">300808.0012</a>, respectively) in 2 unrelated Chinese families with X-linked recessive congenital nystagmus without features of ocular albinism. Female carriers were unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19390656+18523664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Incerti, B., Cortese, K., Pizzigoni, A., Surace, E. M., Varani, S., Coppola, M., Jeffery, G., Seeliger, M., Jaissle, G., Bennett, D. C., Marigo, V., Schiaffino, M. V., Tacchetti, C., Ballabio, A. <strong>Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1.</strong> Hum. Molec. Genet. 9: 2781-2788, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11092754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11092754</a>] [<a href="https://doi.org/10.1093/hmg/9.19.2781" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11092754">Incerti et al. (2000)</a> generated and characterized Oa1-deficient mice by gene targeting. Knockout males were viable, fertile, and phenotypically indistinguishable from wildtype littermates. Ophthalmologic examination showed hypopigmentation of the ocular fundus in mutant animals compared with wildtype. Analysis of the retinofugal pathway revealed a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibers at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE showed the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells suggested that the giant melanosomes may form by abnormal growth of single melanosomes rather than by the fusion of several organelles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11092754" 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="Palmisano, I., Bagnato, P., Palmigiano, A., Innamorati, G., Rotondo, G., Altimare, D., Venturi, C., Sviderskaya, E. V., Piccirillo, R., Coppola, M., Marigo, V., Incerti, B., Ballabio, A., Surace, E. M., Tacchetti, C., Bennett, D. C., Schiaffino, M. V. <strong>The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells.</strong> Hum. Molec. Genet. 17: 3487-3501, 2008. Note: Erratum: Hum. Molec. Genet. 26: 3028-3029, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18697795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18697795</a>] [<a href="https://doi.org/10.1093/hmg/ddn241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18697795">Palmisano et al. (2008)</a> found reduced melanosome number and abnormal melanosome distribution toward the apical pole of Oa1 -/- RPE at embryonic stages that preceded the formation of macromelanosomes. In cultured -/- skin melanocytes, melanosomes were depleted from the perinuclear area and accumulated toward the cell periphery. In Oa1 -/- melanocytes, melanosomes interacted normally with the microtubule cytoskeleton and recruited factors required for actin-mediated melanosome capture; however, Oa1 -/- melanosomes appeared unable to release from the peripheral actin filaments. <a href="#13" class="mim-tip-reference" title="Palmisano, I., Bagnato, P., Palmigiano, A., Innamorati, G., Rotondo, G., Altimare, D., Venturi, C., Sviderskaya, E. V., Piccirillo, R., Coppola, M., Marigo, V., Incerti, B., Ballabio, A., Surace, E. M., Tacchetti, C., Bennett, D. C., Schiaffino, M. V. <strong>The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells.</strong> Hum. Molec. Genet. 17: 3487-3501, 2008. Note: Erratum: Hum. Molec. Genet. 26: 3028-3029, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18697795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18697795</a>] [<a href="https://doi.org/10.1093/hmg/ddn241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18697795">Palmisano et al. (2008)</a> concluded that OA1 plays a regulatory role in distributing melanosomes between microtubule- and actin-based cytoskeletal elements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18697795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>13 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300808[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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<strong>.0001 ALBINISM, OCULAR, TYPE I</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011260" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011260" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011260</a>
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<p>In 4 apparently unrelated families with OA1 (<a href="/entry/300500">300500</a>), <a href="#1" class="mim-tip-reference" title="Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A. <strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong> Nature Genet. 10: 13-19, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647783</a>] [<a href="https://doi.org/10.1038/ng0595-13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647783">Bassi et al. (1995)</a> found an insertional mutation of a CG dinucleotide at position 992 of the cDNA. Such CG dinucleotide insertions have been attributed to the symmetric element GCCG immediately following the insertion site (<a href="#2" class="mim-tip-reference" title="Cooper, D. N., Krawczak, M. <strong>Mechanisms of insertional mutagenesis in human genes causing genetic disease.</strong> Hum. Genet. 87: 409-415, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1652548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1652548</a>] [<a href="https://doi.org/10.1007/BF00197158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1652548">Cooper and Krawczak, 1991</a>). The mutation completely cosegregated with the disease allele in the 4 families and produced a frameshift in the predicted protein product with a subsequent premature stop codon 20 amino acids downstream. The identification of this same mutational event in 4 families from the same region in the Netherlands suggested founder effect. Since all 4 families had multiple affected members in at least 4 generations, it was not possible to trace the origin of the mutation. It is likely that they share a common ancestor. Another such large pedigree on which clinical records date back to the 19th century was identified in Newfoundland by the Canadian National Institute for the Blind (<a href="#7" class="mim-tip-reference" title="Johnson, G. J., Gillan, J. G., Pearce, W. G. <strong>Ocular albinism in Newfoundland.</strong> Canad. J. Ophthal. 6: 237-248, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5125647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5125647</a>]" pmid="5125647">Johnson et al., 1971</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5125647+1652548+7647783" 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">rs62645741 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62645741;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=rs62645741" 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=rs62645741" 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=RCV000084916 OR RCV002280778" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000084916, RCV002280778" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000084916...</a>
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<p>In probands of a British family with OA1 (<a href="/entry/300500">300500</a>), <a href="#17" class="mim-tip-reference" title="Schiaffino, M. V., Bassi, M. T., Galli, L., Renieri, A., Bruttini, M., De Nigris, F., Bergen, A. A. B., Charles, S. J., Yates, J. R. W., Meindl, A., Lewis, R. A., King, R. A., Ballabio, A. <strong>Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.</strong> Hum. Molec. Genet. 4: 2319-2325, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634705</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634705">Schiaffino et al. (1995)</a> identified a 17-bp deletion within exon 1 of the GPR143 gene, producing a frameshift leading to a premature stop codon. <a href="#19" class="mim-tip-reference" title="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> identified the same mutation in probands of an Australian-British family with OA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9529334+8634705" 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 ALBINISM, OCULAR, TYPE I</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">rs137852296 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852296;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=rs137852296" 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=rs137852296" 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=RCV000011262 OR RCV000084931" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011262, RCV000084931" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011262...</a>
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<p>In a patient with OA1 (<a href="/entry/300500">300500</a>), <a href="#19" class="mim-tip-reference" title="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> identified a missense mutation that converted codon 133 from TGG (trp) to CGG (arg) (W133R). The patients also showed developmental delay and renal and immune dysfunction. In another family, the same W133R mutation was found. That family was of interest because a manifesting female had a 45,XO karyotype (Turner syndrome). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529334" 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 ALBINISM, OCULAR, TYPE I</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">rs58933950 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58933950;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=rs58933950" 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=rs58933950" 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=RCV000011263 OR RCV000084936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011263, RCV000084936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011263...</a>
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<p>In a patient with ocular albinism (OA1; <a href="/entry/300500">300500</a>) and giant pigment granules in melanocytes, <a href="#19" class="mim-tip-reference" title="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> demonstrated a mutation changing codon 152 from AGC (ser) to AAC (asn) (S152N) in the OA1 gene. The patient also had Becker-type muscular dystrophy (<a href="/entry/300376">300376</a>), which <a href="#19" class="mim-tip-reference" title="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> concluded was probably coincidental. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529334" 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> rs137852297 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852297;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/rs137852297?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=rs137852297" 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=rs137852297" 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=RCV000011264 OR RCV000084940" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011264, RCV000084940" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011264...</a>
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<p>In a patient with OA1 (<a href="/entry/300500">300500</a>) characterized by the presence of giant pigment granules in melanocytes, <a href="#19" class="mim-tip-reference" title="Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others. <strong>OA1 mutations and deletions in X-linked ocular albinism.</strong> Am. J. Hum. Genet. 62: 800-809, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529334</a>] [<a href="https://doi.org/10.1086/301776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529334">Schnur et al. (1998)</a> identified a thr232-to-lys (T232K) missense mutation resulting from a change of ACG to AAG in the OA1 gene. The mother had a normal fundus examination; the mother and the affected grandfather had 'vitiligo.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 ALBINISM, OCULAR, TYPE I</strong>
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GPR143, TRP133ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852296 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852296;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=rs137852296" 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=rs137852296" 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=RCV000011265 OR RCV000084930" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011265, RCV000084930" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011265...</a>
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<p>In 3 presumably unrelated Danish families with OA1 (<a href="/entry/300500">300500</a>), <a href="#16" class="mim-tip-reference" title="Rosenberg, T., Schwartz, M. <strong>X-linked ocular albinism: prevalence and mutations--a national study.</strong> Europ. J. Hum. Genet. 6: 570-577, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887374</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887374">Rosenberg and Schwartz (1998)</a> found a T-to-A transversion at nucleotide 457 of the OA1 gene that resulted in a trp133-to-arg (W133R) missense mutation in the gene product. Subsequently, 2 of the families were found to be related. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0007 ALBINISM, OCULAR, TYPE I</strong>
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GPR143, 420G-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> rs281865178 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865178;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/rs281865178?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=rs281865178" 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=rs281865178" 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=RCV000084928 OR RCV001824020 OR RCV005042200" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000084928, RCV001824020, RCV005042200" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000084928...</a>
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<p>In a patient with X-linked ocular albinism (OA1; <a href="/entry/300500">300500</a>), <a href="#16" class="mim-tip-reference" title="Rosenberg, T., Schwartz, M. <strong>X-linked ocular albinism: prevalence and mutations--a national study.</strong> Europ. J. Hum. Genet. 6: 570-577, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887374</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887374">Rosenberg and Schwartz (1998)</a> found deletion of exon 2 and part of the flanking introns resulting from a G-to-A transition at nucleotide 420 of the GPR143 gene. The mutation changed the last nucleotide of exon 2, which per se did not cause any amino acid change; however, the mutation changed the consensus sequence of the donor splice site from GCGgt to GCAgt. The most frequent 3-prime exon sequence of the donor splice site is GAG (<a href="#8" class="mim-tip-reference" title="Krawczak, M., Reiss, J., Cooper, D. N. <strong>The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences.</strong> Hum. Genet. 90: 41-54, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1427786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1427786</a>] [<a href="https://doi.org/10.1007/BF00210743" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1427786">Krawczak et al., 1992</a>). The change of the 3-prime sequence of exon 2 to GCA would be expected to weaken or destroy the splicing signal. Such mutations have been found in several genes, e.g., PROC (<a href="/entry/612283">612283</a>) (<a href="#9" class="mim-tip-reference" title="Lind, B., van Solinge, W. W., Schwartz, M., Thorsen, S. <strong>Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.</strong> Blood 82: 2423-2432, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8400292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8400292</a>]" pmid="8400292">Lind et al., 1993</a>), and have been shown to result in exon skipping. The patient with the splice site mutation showed a milder phenotype than did other patients with missense mutations; there was no iris translucency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9887374+8400292+1427786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 ALBINISM, OCULAR, TYPE I</strong>
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GPR143, GLY35ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs62635018 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62635018;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=rs62635018" 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=rs62635018" 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=RCV000011267 OR RCV000084909" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011267, RCV000084909" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011267...</a>
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<p>In a study of 9 families with X-linked ocular albinism (OA1; <a href="/entry/300500">300500</a>), <a href="#16" class="mim-tip-reference" title="Rosenberg, T., Schwartz, M. <strong>X-linked ocular albinism: prevalence and mutations--a national study.</strong> Europ. J. Hum. Genet. 6: 570-577, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887374</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887374">Rosenberg and Schwartz (1998)</a> identified 7 pathogenic mutations. Only 1 of these, gly35 to asp (G35D), had previously been identified (<a href="#17" class="mim-tip-reference" title="Schiaffino, M. V., Bassi, M. T., Galli, L., Renieri, A., Bruttini, M., De Nigris, F., Bergen, A. A. B., Charles, S. J., Yates, J. R. W., Meindl, A., Lewis, R. A., King, R. A., Ballabio, A. <strong>Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.</strong> Hum. Molec. Genet. 4: 2319-2325, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634705</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634705">Schiaffino et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9887374+8634705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 NYSTAGMUS, 6, CONGENITAL, X-LINKED</strong>
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GPR143, SER89PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852298 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852298;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=rs137852298" 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=rs137852298" 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=RCV000011268" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011268" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011268</a>
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<p>In a large 6-generation Chinese family in which 8 males had congenital nystagmus (NYS6; <a href="/entry/300814">300814</a>), <a href="#10" class="mim-tip-reference" title="Liu, J. Y., Ren, X., Yang, X., Guo, T., Yao, Q., Li, L., Dai, X., Zhang, M., Wang, L., Liu, M., Wang, Q. K. <strong>Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation.</strong> J. Hum. Genet. 52: 565-570, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17516023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17516023</a>] [<a href="https://doi.org/10.1007/s10038-007-0152-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17516023">Liu et al. (2007)</a> identified a 266C-T transition in exon 2 of the GPR143 gene, resulting in a ser89-to-phe (S89F) substitution at a highly conserved residue. The mutation was found in 5 affected males and 4 carrier females and was not found in 4 unaffected family members or 200 controls. The pedigree pattern was consistent with X-linked recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17516023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 ALBINISM, OCULAR, TYPE I</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">rs281865183 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865183;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=rs281865183" 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=rs281865183" 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=RCV000084944 OR RCV002280779" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000084944, RCV002280779" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000084944...</a>
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<p>In affected members of a 3-generation family with variable features of ocular albinism (<a href="/entry/300500">300500</a>), <a href="#15" class="mim-tip-reference" title="Preising, M., Op de Laak, J.-P., Lorenz, B. <strong>Deletion in the OA1 gene in a family with congenital X linked nystagmus.</strong> Brit. J. Ophthal. 85: 1098-1103, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11520764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11520764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11520764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/bjo.85.9.1098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11520764">Preising et al. (2001)</a> identified a 14-bp deletion beginning at nucleotide 816 and affecting the splice donor signal of intron 6 of the GPR143 gene. The male proband was diagnosed with OA1 at age 3 months with typical clinical features, including congenital nystagmus, iris translucency, macular hypoplasia, fundus hypopigmentation, and normal pigmentation of skin and hair. Examination at age 4 years showed increased pigmentation of the iris and fundus and improved visual acuity. A 51-year-old maternal uncle also had congenital nystagmus, clear macular hypoplasia and stromal focal hypopigmentation of the iris, but no iris translucency or fundus hypopigmentation. Macromelanosomes were present on skin biopsy. A 79-year-old maternal relative had congenital nystagmus and high myopia with macular change, but no iris translucency. Two carrier females had mosaic pattern of hypopigmented retinal epithelium, consistent with a carrier status of ocular albinism. RT-PCR studies showed that the 14-bp deletion resulted in a frameshift and premature termination of the protein at residue 259. The resulting gene product lacks the last transmembrane domain from the extracellular loop 3 to the C terminus. <a href="#15" class="mim-tip-reference" title="Preising, M., Op de Laak, J.-P., Lorenz, B. <strong>Deletion in the OA1 gene in a family with congenital X linked nystagmus.</strong> Brit. J. Ophthal. 85: 1098-1103, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11520764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11520764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11520764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/bjo.85.9.1098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11520764">Preising et al. (2001)</a> suggested that this mutation results in a hypomorphic allele that causes impaired membrane fusion of melanosomes and the plasma membrane. They proposed a model of OA1 in this family that allowed increase of pigmentation with age. Thus, postnatal normalization of the extracellular dopamine levels due to delayed distribution and membrane budding or fusion of melanosomes in melanocytes could result in increasing pigmentation and a seemingly variable phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11520764" 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>.0011 NYSTAGMUS 6, CONGENITAL, X-LINKED</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011270 OR RCV003398480" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011270, RCV003398480" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011270...</a>
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<p>In affected males in a 4-generation Chinese family with congenital nystagmus (<a href="/entry/300814">300814</a>), <a href="#23" class="mim-tip-reference" title="Zhou, P., Wang, Z., Zhang, J., Hu, L., Kong, X. <strong>Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus.</strong> Molec. Vis. 14: 1015-1019, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18523664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18523664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18523664[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="18523664">Zhou et al. (2008)</a> identified a 37-bp deletion in exon 1 of the GPR143 gene, predicted to result in a frameshift and premature termination. The mutant transcript is likely to be degraded by nonsense-mediated mRNA decay and loss of function. All male mutation carriers had X-linked congenital nystagmus without evidence of ocular albinism. Obligate mutation carriers did not have nystagmus, consistent with X-linked recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18523664" 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=RCV000011271 OR RCV002512969" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011271, RCV002512969" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011271...</a>
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<p>In affected members of a Chinese family with X-linked congenital nystagmus (<a href="/entry/300814">300814</a>), <a href="#14" class="mim-tip-reference" title="Peng, Y., Meng, Y., Wang, Z., Qin, M., Li, X., Dian, Y., Huang, S. <strong>A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus.</strong> Molec. Vis. 15: 810-814, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19390656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19390656</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19390656[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19390656">Peng et al. (2009)</a> identified a 19-bp duplication (291_309) in exon 1 of the GPR143 gene, resulting in a frameshift, premature termination, and nonsense-mediated mRNA decay. All patients were male, and had binocular spontaneous horizontal oscillations without head nodding. They all had reduced vision, amblyopia, and mild compound hypermetropic astigmatism. None of the patients had classic features of ocular albinism. Female carriers were unaffected, consistent with X-linked recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19390656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 ALBINISM, OCULAR, TYPE I</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000022876" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022876" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022876</a>
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<p>In a Chinese patient with ocular albinism (OA1; <a href="/entry/300500">300500</a>), <a href="#22" class="mim-tip-reference" title="Xiao, X., Zhang, Q. <strong>Iris hyperpigmentation in a Chinese family with ocular albinism and the GPR143 mutation.</strong> Am. J. Med. Genet. 149A: 1786-1788, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19610097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19610097</a>] [<a href="https://doi.org/10.1002/ajmg.a.32818" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19610097">Xiao and Zhang (2009)</a> identified a deletion of exons 1 and 2 of the GPR143 gene. The patient and his carrier mother both demonstrated an unusual phenotype of iris hyperpigmentation without translucency, with apparent mosaic pigmentation of the fundus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19610097" 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="Bassi1995" class="mim-anchor"></a>
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Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A.
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<strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong>
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Nature Genet. 10: 13-19, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647783" 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/ng0595-13" target="_blank">Full Text</a>]
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Cooper, D. N., Krawczak, M.
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<strong>Mechanisms of insertional mutagenesis in human genes causing genetic disease.</strong>
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Hum. Genet. 87: 409-415, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1652548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1652548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1652548" 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/BF00197158" target="_blank">Full Text</a>]
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d'Addio, M., Pizzigoni, A., Bassi, M. T., Baschirotto, C., Valetti, C., Incerti, B., Clementi, M., De Luca, M., Ballabio, A., Schiaffino, M. V.
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<strong>Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.</strong>
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Hum. Molec. Genet. 9: 3011-3018, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11115845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11115845</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11115845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.20.3011" target="_blank">Full Text</a>]
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Dinulos, M. B., Bassi, M. T., Rugarli, E. I., Chapman, V., Ballabio, A., Disteche, C. M.
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<strong>A new region of conservation is defined between human and mouse X chromosomes.</strong>
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Genomics 35: 244-247, 1996.
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[<a href="https://doi.org/10.1006/geno.1996.0347" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp415" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/9.19.2781" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00210743" target="_blank">Full Text</a>]
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<strong>The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis.</strong>
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Molec. Cell. Biol. 24: 6550-6559, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15254223[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=15254223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.24.15.6550-6559.2004" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Xiao2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xiao, X., Zhang, Q.
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<strong>Iris hyperpigmentation in a Chinese family with ocular albinism and the GPR143 mutation.</strong>
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Am. J. Med. Genet. 149A: 1786-1788, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19610097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19610097</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19610097" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32818" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Zhou2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhou, P., Wang, Z., Zhang, J., Hu, L., Kong, X.
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<strong>Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus.</strong>
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Molec. Vis. 14: 1015-1019, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18523664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18523664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18523664[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=18523664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</li>
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</ol>
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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="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 6/10/2011
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 1/15/2010<br>Patricia A. Hartz - updated : 11/9/2009
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross : 11/9/2009
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/27/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 07/13/2018<br>carol : 09/05/2013<br>wwang : 6/16/2011<br>terry : 6/10/2011<br>wwang : 11/8/2010<br>terry : 10/28/2010<br>carol : 5/4/2010<br>ckniffin : 1/15/2010<br>mgross : 11/9/2009<br>mgross : 11/9/2009
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</span>
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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 class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300808
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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G PROTEIN-COUPLED RECEPTOR 143; GPR143
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-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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OA1 GENE
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GPR143</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 78642008;
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<strong>ICD10CM:</strong> E70.310;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xp22.2
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Genomic coordinates <span class="small">(GRCh38)</span> : X:9,725,346-9,778,602 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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Xp22.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Nystagmus 6, congenital, X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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300814
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</span>
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</td>
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<td>
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<span class="mim-font">
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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Ocular albinism, type I, Nettleship-Falls type
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</span>
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</td>
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<td>
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<span class="mim-font">
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300500
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</span>
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</td>
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<td>
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<span class="mim-font">
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X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
|
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>GPR143 is a G protein-coupled receptor (GPCR) that is exclusively expressed by melanocytes and retinal pigment epithelium (RPE). Unlike other GPCRs, GPR143 is not localized to the cell surface, but is exclusively found on the membranes of intracellular organelles, namely late endosomes/lysosomes and melanosomes (summary by Palmisano et al. (2008)). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By hybridization of the ocular albinism type I (OA1; 300500) critical region in 4 patients to a human retina cDNA library, followed by RACE-PCR analysis, Bassi et al. (1995) cloned GPR143. RT-PCR analysis detected a 1.6-kb transcript that was expressed at high levels in RNA samples from retina, including RPE, and from melanoma, with weak expression in brain and adrenal gland. The deduced 424-amino acid GPR143 protein has at least 6 putative transmembrane domains. </p><p>Newton et al. (1996) cloned and characterized mouse Gpr143, which they referred to as Moa1. Two Moa1 variants were isolated from a melanoma cDNA library and predicted proteins of 405 and 249 amino acids with 6 and 2 transmembrane-spanning regions, respectively. In adult tissues, both Moa1 isoforms were detected in the eye by Northern hybridization. In neonatal tissues, Moa1 RNA was detected in both skin and eye by Northern hybridization and was not affected by the absence of pigment in mice carrying the 'albino' mutation or by the type of pigment synthesized, i.e., eumelanin or pheomelanin, in mice carrying the 'black-and-tan' mutation. Expression of Moa1 RNA was not detected in embryonic tissues by Northern analysis or by in situ hybridization despite the active synthesis of ocular pigment by embryonic stage E16.5. </p><p>By immunogold electron microscopy of human melanocytic cell line MNT-1, Giordano et al. (2009) showed that GPR143 was widely distributed throughout the endo-melanosomal system but that most of the endogenous protein was localized in unpigmented stage II melanosomes. </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>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Schiaffino et al. (1995) determined that the GPR143 gene contains 9 exons and spans 40 kb. </p><p>Vetrini et al. (2004) identified several putative transcription factor-binding sites in the 5-prime proximal region of the OA1 promoter, including sites for SP1 (189906), GBX2 (601135), HES1 (139605), and MITF (156845). There is no TATA box. The mouse Oa1 promoter region shows a nearly identical organization. Using several in vitro and in vivo approaches, Vetrini et al. (2004) confirmed that the MITF site, an E-box at position -28 from the transcription start site, was bound by the MITF-M isoform and was functional in pigmented mouse and human cells. MITF-M could drive expression of OA1 in melanocytes and retinal pigment epithelium. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
|
|
<p>Bassi et al. (1995) mapped the GPR143 gene to chromosome Xp22.3-p22.2, approximately 20 kb on the telomeric side of the APXL gene (SHROOM2; 300103). APXL spans 80 of the 110 kb of the OA1 critical region. </p><p>Comparative mapping of the X chromosome in eutherian mammals has revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Dinulos et al. (1996) mapped the murine homologs of OA1 and APXL. They found that the 2 genes map to bands F2-F3 in both M. spretus and the laboratory strains C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. </p><p>Interspecific backcross mapping by Newton et al. (1996) yielded a map order and distances (in cM) of cen-Moa1-3.1 +/- 1.8-Piga (311770)-2.1 +/- 1.5-Amel (AMELX; 300391), indicating that Moa1 is located much farther away from the pseudoautosomal region than its human homolog. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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<span class="mim-text-font">
|
|
<p>GPCRs participate in the most common signal transduction system at the plasma membrane. The wide distribution of heterotrimeric G proteins in the internal membranes suggests that a similar signaling mechanism might also be used at intracellular locations. Schiaffino et al. (1999) provided structural evidence that the protein product of the OA1 gene, a pigment cell-specific integral membrane glycoprotein, represents a novel member of the GPCR superfamily and demonstrated that it binds heterotrimeric G proteins. Moreover, they showed that OA1 is not found at the plasma membrane, being instead targeted to specialized intracellular organelles, the melanosomes. The data suggested that OA1 represents the first example of an exclusively intracellular GPCR and supported the hypothesis that GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells. </p><p>Giordano et al. (2009) used siRNA inactivation of GPR143 and combined morphologic and biochemical methods to investigate melanosome ultrastructure, melanosomal protein localization and expression in human pigmented melanocytic cells. GPR143 loss of function led to decreased pigmentation and caused formation of enlarged aberrant premelanosomes harboring disorganized fibrillar structures and displaying proteins of mature melanosomes and lysosomes at their membrane. GPR143 interacted biochemically with the premelanosomal protein MART1 (MLANA; 605513). Inactivation of MART1 by siRNA led to decreased stability of GPR143 and was accompanied by similar defects in premelanosome biogenesis and composition. Giordano et al. (2009) concluded that melanosome composition and identity are regulated at early stages by GPR143 and that MART1 likely acts as an escort protein for GPR143. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p><strong><em>Ocular Albinism Type I</em></strong></p><p>
|
|
Bassi et al. (1995) identified 5 patients with OA1 (300500) who were carrying mutations within the GPR143 gene. Five intragenic deletions and a 2-bp insertion resulting in a premature stop codon (300808.0001) were identified by DNA analysis of patients with OA1. Some of these deletions were not overlapping, making it highly unlikely that the mutation involved in OA1 is located in an intron of the gene. Fine molecular characterization of the gene in 1 patient demonstrated that the deletion removed part of a coding exon. The APXL gene was completely deleted in 1 patient with isolated OA1. However, an extensive search for point mutations was performed in the 4,848-bp coding region of APXL from 57 patients and no functionally relevant mutation was identified. </p><p>Schiaffino et al. (1995) screened the entire OA1 coding region and 5-prime and 3-prime sequences for mutations and detected mutations in only one-third (21 of 60) of their patients with OA, including 2 frameshifts (e.g., 300808.0002) and a splice site mutation leading to truncated OA1 proteins, a deletion of a threonine codon at position 290, and 4 missense mutations (e.g., 300808.0008), 2 of which involved amino acids located within putative transmembrane domains. </p><p>Schnur et al. (1998) reported results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian OA probands, including 5 with additional, nonocular phenotypic abnormalities (Schnur et al., 1994). They detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2 to 8. They also identified 8 novel missense mutations that clustered within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. All told, 26 (approximately 90%) of 29 probands had detectable alterations in the OA1 gene, thus confirming that OA1 is the major locus for X-linked OA. </p><p>In Denmark, Rosenberg and Schwartz (1998) performed a retrospective survey of 112 patients with ocular albinism identified in a national register, including 60 male patients with proven or presumed X-linked ocular albinism. Based on the birth year cohorts 1960 to 1989, a point prevalence for OA1 at birth of 1 in 60,000 live born was calculated. They identified 14 OA1 families in the Danish population and obtained DNA from affected persons in 9 families. Mutation analysis demonstrated 7 presumed pathogenic mutations in the 9 families: 5 single nucleotide substitutions predicting a change of conserved amino acids, including G35D (300808.0008) and W133R (300808.0006), when compared with the mouse OA1 homolog, 1 deletion leading to the skipping of exon 2, and 1 example of a single nucleotide substitution expected to affect the 5-prime splice site of intron 2 (300808.0007). Subsequent genealogic investigations in the 3 families harboring the same mutation, W133R, disclosed that 2 of the 3 belonged to the same family. Clinical examination failed to identify any phenotype-genotype pattern except for the finding of a milder phenotype lacking iris translucency in the patient with the 5-prime splice site mutation of intron 2. </p><p>D'Addio et al. (2000) characterized 19 independent missense mutations with respect to processing and subcellular distribution on expression in COS-7 cells. Eleven of the 19 OA1 mutants (approximately 60%) were retained in the endoplasmic reticulum, showing defective intracellular transport and glycosylation, consistent with protein misfolding. The remaining 8 OA1 mutants (approximately 40%) displayed sorting and processing behaviors indistinguishable from those of the wildtype protein. Most of the latter mutations clustered within the second and third cytosolic loops, 2 regions that in canonical GPCRs are known to be critical for their downstream signaling, including G protein coupling and effector activation. </p><p>Oetting (2002) found that a total of 25 missense, 2 nonsense, 9 frameshift, and 5 splicing mutations in the OA1 gene had been reported in association with type I ocular albinism. There were also reports of several deletions of some or all exons of the OA1 gene with deletions of exon 2 resulting from unequal crossing-over, due to flanking Alu repeats. Oetting (2002) referred to an albinism database website. </p><p>In a Chinese patient with ocular albinism, Xiao and Zhang (2009) identified an intragenic deletion in the GPR143 gene (300808.0013). </p><p><strong><em>X-linked Congenital Nystagmus 6</em></strong></p><p>
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In a large 6-generation Chinese family with congenital nystagmus as the main feature (NYS6; 300814), Liu et al. (2007) analyzed 21 candidate genes and identified a missense mutation in the GPR143 gene (S89F; 300808.0009) in affected males and carrier females. </p><p>Zhou et al. (2008) and Peng et al. (2009) identified mutations in the GPR143 gene (300808.0011 and 300808.0012, respectively) in 2 unrelated Chinese families with X-linked recessive congenital nystagmus without features of ocular albinism. Female carriers were unaffected. </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>Incerti et al. (2000) generated and characterized Oa1-deficient mice by gene targeting. Knockout males were viable, fertile, and phenotypically indistinguishable from wildtype littermates. Ophthalmologic examination showed hypopigmentation of the ocular fundus in mutant animals compared with wildtype. Analysis of the retinofugal pathway revealed a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibers at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE showed the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells suggested that the giant melanosomes may form by abnormal growth of single melanosomes rather than by the fusion of several organelles. </p><p>Palmisano et al. (2008) found reduced melanosome number and abnormal melanosome distribution toward the apical pole of Oa1 -/- RPE at embryonic stages that preceded the formation of macromelanosomes. In cultured -/- skin melanocytes, melanosomes were depleted from the perinuclear area and accumulated toward the cell periphery. In Oa1 -/- melanocytes, melanosomes interacted normally with the microtubule cytoskeleton and recruited factors required for actin-mediated melanosome capture; however, Oa1 -/- melanosomes appeared unable to release from the peripheral actin filaments. Palmisano et al. (2008) concluded that OA1 plays a regulatory role in distributing melanosomes between microtubule- and actin-based cytoskeletal elements. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 ALBINISM, OCULAR, TYPE I</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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GPR143, 2-BP INS, NT992
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<br />
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ClinVar: RCV000011260
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 apparently unrelated families with OA1 (300500), Bassi et al. (1995) found an insertional mutation of a CG dinucleotide at position 992 of the cDNA. Such CG dinucleotide insertions have been attributed to the symmetric element GCCG immediately following the insertion site (Cooper and Krawczak, 1991). The mutation completely cosegregated with the disease allele in the 4 families and produced a frameshift in the predicted protein product with a subsequent premature stop codon 20 amino acids downstream. The identification of this same mutational event in 4 families from the same region in the Netherlands suggested founder effect. Since all 4 families had multiple affected members in at least 4 generations, it was not possible to trace the origin of the mutation. It is likely that they share a common ancestor. Another such large pedigree on which clinical records date back to the 19th century was identified in Newfoundland by the Canadian National Institute for the Blind (Johnson et al., 1971). </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 ALBINISM, OCULAR, TYPE I</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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GPR143, 17-BP DEL
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<br />
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SNP: rs62645741,
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ClinVar: RCV000084916, RCV002280778
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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 probands of a British family with OA1 (300500), Schiaffino et al. (1995) identified a 17-bp deletion within exon 1 of the GPR143 gene, producing a frameshift leading to a premature stop codon. Schnur et al. (1998) identified the same mutation in probands of an Australian-British family with OA1. </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 ALBINISM, OCULAR, TYPE I</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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GPR143, TRP133ARG
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<br />
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SNP: rs137852296,
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ClinVar: RCV000011262, RCV000084931
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with OA1 (300500), Schnur et al. (1998) identified a missense mutation that converted codon 133 from TGG (trp) to CGG (arg) (W133R). The patients also showed developmental delay and renal and immune dysfunction. In another family, the same W133R mutation was found. That family was of interest because a manifesting female had a 45,XO karyotype (Turner syndrome). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 ALBINISM, OCULAR, TYPE I</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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GPR143, SER152ASN
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<br />
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SNP: rs58933950,
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ClinVar: RCV000011263, RCV000084936
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with ocular albinism (OA1; 300500) and giant pigment granules in melanocytes, Schnur et al. (1998) demonstrated a mutation changing codon 152 from AGC (ser) to AAC (asn) (S152N) in the OA1 gene. The patient also had Becker-type muscular dystrophy (300376), which Schnur et al. (1998) concluded was probably coincidental. </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 ALBINISM, OCULAR, TYPE I</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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GPR143, THR232LYS
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<br />
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SNP: rs137852297,
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gnomAD: rs137852297,
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|
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ClinVar: RCV000011264, RCV000084940
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with OA1 (300500) characterized by the presence of giant pigment granules in melanocytes, Schnur et al. (1998) identified a thr232-to-lys (T232K) missense mutation resulting from a change of ACG to AAG in the OA1 gene. The mother had a normal fundus examination; the mother and the affected grandfather had 'vitiligo.' </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>.0006 ALBINISM, OCULAR, TYPE I</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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GPR143, TRP133ARG
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<br />
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|
|
SNP: rs137852296,
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|
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ClinVar: RCV000011265, RCV000084930
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 presumably unrelated Danish families with OA1 (300500), Rosenberg and Schwartz (1998) found a T-to-A transversion at nucleotide 457 of the OA1 gene that resulted in a trp133-to-arg (W133R) missense mutation in the gene product. Subsequently, 2 of the families were found to be related. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ALBINISM, OCULAR, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GPR143, 420G-A
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<br />
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|
|
SNP: rs281865178,
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|
|
gnomAD: rs281865178,
|
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|
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ClinVar: RCV000084928, RCV001824020, RCV005042200
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|
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|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked ocular albinism (OA1; 300500), Rosenberg and Schwartz (1998) found deletion of exon 2 and part of the flanking introns resulting from a G-to-A transition at nucleotide 420 of the GPR143 gene. The mutation changed the last nucleotide of exon 2, which per se did not cause any amino acid change; however, the mutation changed the consensus sequence of the donor splice site from GCGgt to GCAgt. The most frequent 3-prime exon sequence of the donor splice site is GAG (Krawczak et al., 1992). The change of the 3-prime sequence of exon 2 to GCA would be expected to weaken or destroy the splicing signal. Such mutations have been found in several genes, e.g., PROC (612283) (Lind et al., 1993), and have been shown to result in exon skipping. The patient with the splice site mutation showed a milder phenotype than did other patients with missense mutations; there was no iris translucency. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
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|
</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ALBINISM, OCULAR, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
GPR143, GLY35ASP
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<br />
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|
|
SNP: rs62635018,
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|
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ClinVar: RCV000011267, RCV000084909
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|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a study of 9 families with X-linked ocular albinism (OA1; 300500), Rosenberg and Schwartz (1998) identified 7 pathogenic mutations. Only 1 of these, gly35 to asp (G35D), had previously been identified (Schiaffino et al., 1995). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NYSTAGMUS, 6, CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
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GPR143, SER89PHE
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<br />
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|
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SNP: rs137852298,
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|
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ClinVar: RCV000011268
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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 large 6-generation Chinese family in which 8 males had congenital nystagmus (NYS6; 300814), Liu et al. (2007) identified a 266C-T transition in exon 2 of the GPR143 gene, resulting in a ser89-to-phe (S89F) substitution at a highly conserved residue. The mutation was found in 5 affected males and 4 carrier females and was not found in 4 unaffected family members or 200 controls. The pedigree pattern was consistent with X-linked recessive inheritance. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0010 ALBINISM, OCULAR, TYPE I</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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GPR143, 14-BP DEL, NT816
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<br />
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SNP: rs281865183,
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ClinVar: RCV000084944, RCV002280779
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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 affected members of a 3-generation family with variable features of ocular albinism (300500), Preising et al. (2001) identified a 14-bp deletion beginning at nucleotide 816 and affecting the splice donor signal of intron 6 of the GPR143 gene. The male proband was diagnosed with OA1 at age 3 months with typical clinical features, including congenital nystagmus, iris translucency, macular hypoplasia, fundus hypopigmentation, and normal pigmentation of skin and hair. Examination at age 4 years showed increased pigmentation of the iris and fundus and improved visual acuity. A 51-year-old maternal uncle also had congenital nystagmus, clear macular hypoplasia and stromal focal hypopigmentation of the iris, but no iris translucency or fundus hypopigmentation. Macromelanosomes were present on skin biopsy. A 79-year-old maternal relative had congenital nystagmus and high myopia with macular change, but no iris translucency. Two carrier females had mosaic pattern of hypopigmented retinal epithelium, consistent with a carrier status of ocular albinism. RT-PCR studies showed that the 14-bp deletion resulted in a frameshift and premature termination of the protein at residue 259. The resulting gene product lacks the last transmembrane domain from the extracellular loop 3 to the C terminus. Preising et al. (2001) suggested that this mutation results in a hypomorphic allele that causes impaired membrane fusion of melanosomes and the plasma membrane. They proposed a model of OA1 in this family that allowed increase of pigmentation with age. Thus, postnatal normalization of the extracellular dopamine levels due to delayed distribution and membrane budding or fusion of melanosomes in melanocytes could result in increasing pigmentation and a seemingly variable phenotype. </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>.0011 NYSTAGMUS 6, CONGENITAL, X-LINKED</strong>
|
|
</span>
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</h4>
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</div>
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<span class="mim-text-font">
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GPR143, 37-BP DEL
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<br />
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ClinVar: RCV000011270, RCV003398480
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected males in a 4-generation Chinese family with congenital nystagmus (300814), Zhou et al. (2008) identified a 37-bp deletion in exon 1 of the GPR143 gene, predicted to result in a frameshift and premature termination. The mutant transcript is likely to be degraded by nonsense-mediated mRNA decay and loss of function. All male mutation carriers had X-linked congenital nystagmus without evidence of ocular albinism. Obligate mutation carriers did not have nystagmus, consistent with X-linked recessive inheritance. </p>
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<h4>
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<span class="mim-font">
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<strong>.0012 NYSTAGMUS 6, CONGENITAL, X-LINKED</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GPR143, 19-BP DUP
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ClinVar: RCV000011271, RCV002512969
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Chinese family with X-linked congenital nystagmus (300814), Peng et al. (2009) identified a 19-bp duplication (291_309) in exon 1 of the GPR143 gene, resulting in a frameshift, premature termination, and nonsense-mediated mRNA decay. All patients were male, and had binocular spontaneous horizontal oscillations without head nodding. They all had reduced vision, amblyopia, and mild compound hypermetropic astigmatism. None of the patients had classic features of ocular albinism. Female carriers were unaffected, consistent with X-linked recessive inheritance. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>.0013 ALBINISM, OCULAR, TYPE I</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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GPR143, EX1-2DEL
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<br />
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ClinVar: RCV000022876
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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 Chinese patient with ocular albinism (OA1; 300500), Xiao and Zhang (2009) identified a deletion of exons 1 and 2 of the GPR143 gene. The patient and his carrier mother both demonstrated an unusual phenotype of iris hyperpigmentation without translucency, with apparent mosaic pigmentation of the fundus. </p>
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</span>
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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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Bassi, M. T., Schiaffino, M. V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A. A. B., Lewis, R. A., Ballabio, A.
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<strong>Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.</strong>
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Nature Genet. 10: 13-19, 1995.
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Cooper, D. N., Krawczak, M.
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<strong>Mechanisms of insertional mutagenesis in human genes causing genetic disease.</strong>
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Hum. Genet. 87: 409-415, 1991.
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d'Addio, M., Pizzigoni, A., Bassi, M. T., Baschirotto, C., Valetti, C., Incerti, B., Clementi, M., De Luca, M., Ballabio, A., Schiaffino, M. V.
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<strong>Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.</strong>
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Giordano, F., Bonetti, C., Surace, E. M., Marigo, V., Raposo, G.
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<strong>The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.</strong>
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Hum. Molec. Genet. 18: 4530-4545, 2009.
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Incerti, B., Cortese, K., Pizzigoni, A., Surace, E. M., Varani, S., Coppola, M., Jeffery, G., Seeliger, M., Jaissle, G., Bennett, D. C., Marigo, V., Schiaffino, M. V., Tacchetti, C., Ballabio, A.
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<strong>Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1.</strong>
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Hum. Molec. Genet. 9: 2781-2788, 2000.
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[PubMed: 11092754]
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Johnson, G. J., Gillan, J. G., Pearce, W. G.
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<strong>Ocular albinism in Newfoundland.</strong>
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Canad. J. Ophthal. 6: 237-248, 1971.
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Krawczak, M., Reiss, J., Cooper, D. N.
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<strong>The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences.</strong>
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Hum. Genet. 90: 41-54, 1992.
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Lind, B., van Solinge, W. W., Schwartz, M., Thorsen, S.
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<strong>Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.</strong>
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Blood 82: 2423-2432, 1993.
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[PubMed: 8400292]
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Liu, J. Y., Ren, X., Yang, X., Guo, T., Yao, Q., Li, L., Dai, X., Zhang, M., Wang, L., Liu, M., Wang, Q. K.
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<strong>Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation.</strong>
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J. Hum. Genet. 52: 565-570, 2007.
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[PubMed: 17516023]
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Newton, J. M., Orlow, S. J., Barsh, G. S.
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<strong>Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene.</strong>
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Genomics 37: 219-225, 1996.
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Oetting, W. S.
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<strong>New insights into ocular albinism type 1 (OA1): mutations and polymorphisms of the OA1 gene.</strong>
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Hum. Mutat. 19: 85-92, 2002.
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[PubMed: 11793467]
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Palmisano, I., Bagnato, P., Palmigiano, A., Innamorati, G., Rotondo, G., Altimare, D., Venturi, C., Sviderskaya, E. V., Piccirillo, R., Coppola, M., Marigo, V., Incerti, B., Ballabio, A., Surace, E. M., Tacchetti, C., Bennett, D. C., Schiaffino, M. V.
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<strong>The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells.</strong>
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Hum. Molec. Genet. 17: 3487-3501, 2008. Note: Erratum: Hum. Molec. Genet. 26: 3028-3029, 2017.
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[PubMed: 18697795]
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[Full Text: https://doi.org/10.1093/hmg/ddn241]
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Peng, Y., Meng, Y., Wang, Z., Qin, M., Li, X., Dian, Y., Huang, S.
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<strong>A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus.</strong>
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Molec. Vis. 15: 810-814, 2009.
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[PubMed: 19390656]
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Preising, M., Op de Laak, J.-P., Lorenz, B.
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<strong>Deletion in the OA1 gene in a family with congenital X linked nystagmus.</strong>
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Brit. J. Ophthal. 85: 1098-1103, 2001.
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[PubMed: 11520764]
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[Full Text: https://doi.org/10.1136/bjo.85.9.1098]
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Rosenberg, T., Schwartz, M.
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<strong>X-linked ocular albinism: prevalence and mutations--a national study.</strong>
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Europ. J. Hum. Genet. 6: 570-577, 1998.
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<p class="mim-text-font">
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Schiaffino, M. V., Bassi, M. T., Galli, L., Renieri, A., Bruttini, M., De Nigris, F., Bergen, A. A. B., Charles, S. J., Yates, J. R. W., Meindl, A., Lewis, R. A., King, R. A., Ballabio, A.
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<strong>Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.</strong>
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Hum. Molec. Genet. 4: 2319-2325, 1995.
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[PubMed: 8634705]
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<p class="mim-text-font">
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Schiaffino, M. V., d'Addio, M., Alloni, A., Baschirotto, C., Valetti, C., Cortese, K., Puri, C., Bassi, M. T., Colla, C., De Luca, M., Tacchetti, C., Ballabio, A.
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<strong>Ocular albinism: evidence for a defect in an intracellular signal transduction system.</strong>
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Nature Genet. 23: 108-112, 1999.
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<p class="mim-text-font">
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Schnur, R. E., Gao, M., Wick, P. A., Keller, M., Benke, P. J., Edwards, M. J., Grix, A. W., Hockey, A., Jung, J. H., Kidd, K. K., Kistenmacher, M., Levin, A. V., and 11 others.
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<strong>OA1 mutations and deletions in X-linked ocular albinism.</strong>
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Am. J. Hum. Genet. 62: 800-809, 1998.
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</li>
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<li>
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<p class="mim-text-font">
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Schnur, R. E., Wick, P. A., Bailey, C., Rebbeck, T., Weleber, R. G., Wagstaff, J., Grix, A. W., Pagon, R. A., Hockey, A., Edwards, M. J.
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<strong>Phenotypic variability in X-linked ocular albinism: relationship to linkage genotypes.</strong>
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Am. J. Hum. Genet. 55: 484-496, 1994.
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[PubMed: 7915878]
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</li>
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<li>
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<p class="mim-text-font">
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Vetrini, F., Auricchio, A., Du, J., Angeletti, B., Fisher, D. E., Ballabio, A., Marigo, V.
|
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<strong>The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis.</strong>
|
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Molec. Cell. Biol. 24: 6550-6559, 2004.
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[PubMed: 15254223]
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[Full Text: https://doi.org/10.1128/MCB.24.15.6550-6559.2004]
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</p>
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<li>
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<p class="mim-text-font">
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Xiao, X., Zhang, Q.
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<strong>Iris hyperpigmentation in a Chinese family with ocular albinism and the GPR143 mutation.</strong>
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Am. J. Med. Genet. 149A: 1786-1788, 2009.
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[PubMed: 19610097]
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[Full Text: https://doi.org/10.1002/ajmg.a.32818]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zhou, P., Wang, Z., Zhang, J., Hu, L., Kong, X.
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<strong>Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus.</strong>
|
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Molec. Vis. 14: 1015-1019, 2008.
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[PubMed: 18523664]
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</p>
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</li>
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</ol>
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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 class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 6/10/2011<br>George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 1/15/2010<br>Patricia A. Hartz - updated : 11/9/2009
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</span>
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</div>
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</div>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross : 11/9/2009
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<span class="text-nowrap mim-text-font">
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Edit History:
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