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<title>
Entry
- *600179 - GUANYLATE CYCLASE 2D, RETINAL; GUCY2D
- OMIM
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<span class="h4">*600179</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation">
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9658;</span> Genome
</a>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000132518;t=ENST00000254854" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=3000" 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>
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600179" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
<span class="panel-title">
<span class="small">
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9658;</span> DNA
</a>
</span>
</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000132518;t=ENST00000254854" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000180,XM_011523816" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000180" 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>
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600179" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
<span class="panel-title">
<span class="small">
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9658;</span> Protein
</a>
</span>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://hprd.org/summary?hprd_id=02550&isoform_id=02550_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>
<div><a href="https://www.proteinatlas.org/search/GUCY2D" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/protein/620040,623415,1345920,2695890,4504217,90110499,119610509,767992038,2462554798" 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>
<div><a href="https://www.uniprot.org/uniprotkb/Q02846" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
<span class="panel-title">
<span class="small">
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Gene Info</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="http://biogps.org/#goto=genereport&id=3000" 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>
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000132518;t=ENST00000254854" 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>
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=GUCY2D" 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>
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=GUCY2D" 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>
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+3000" 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>
<dd><a href="http://v1.marrvel.org/search/gene/GUCY2D" 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>
<dd><a href="https://monarchinitiative.org/NCBIGene:3000" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
<div><a href="https://www.ncbi.nlm.nih.gov/gene/3000" 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>
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000254854.5&hgg_start=8002615&hgg_end=8020342&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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:4689" 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>
<div><a href="https://medlineplus.gov/genetics/gene/gucy2d" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600179[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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
<span class="panel-title">
<span class="small">
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9660;</span> Variation
</a>
</span>
</span>
</div>
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600179[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>
<div><a href="https://www.deciphergenomics.org/gene/GUCY2D/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000132518" 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>
<div><a href="https://www.ebi.ac.uk/gwas/search?query=GUCY2D" 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&nbsp;</a></div>
<div><a href="https://www.gwascentral.org/search?q=GUCY2D" 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&nbsp;</a></div>
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GUCY2D" 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>
<div><a href="http://www.retina-international.org/files/sci-news/gcmut.htm" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GUCY2D&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>
<div><a href="https://www.pharmgkb.org/gene/PA187" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/gene/HGNC:4689" 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>
<div><a href="https://flybase.org/reports/FBgn0085386.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
<div><a href="https://www.mousephenotype.org/data/genes/MGI:105123" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
<div><a href="http://v1.marrvel.org/search/gene/GUCY2D#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>
<div><a href="http://www.informatics.jax.org/marker/MGI:105123" 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>
<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>
<div><a href="https://www.ncbi.nlm.nih.gov/gene/3000/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>
<div><a href="https://omia.org/results?search_type=advanced&omia_id=001929,002646" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
<div><a href="https://www.orthodb.org/?ncbi=3000" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
<div><a href="https://zfin.org/ZDB-GENE-011128-7" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
<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">
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cellular Pathways</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3000" 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>
<div><a href="https://reactome.org/content/query?q=GUCY2D&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>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<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.">
&nbsp;
</span>
</span>
</div>
<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">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
&nbsp;
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Gene description">
<span class="text-danger"><strong>*</strong></span>
600179
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
GUANYLATE CYCLASE 2D, RETINAL; GUCY2D
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
GUC2D<br />
GUANYLATE CYCLASE 2D, MEMBRANE<br />
GUCY2E, MOUSE, HOMOLOG OF<br />
ROD OUTER SEGMENT MEMBRANE GUANYLATE CYCLASE; ROSGC<br />
RETGC<br />
RETGC1
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<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=GUCY2D" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GUCY2D</a></em></strong>
</span>
</p>
</div>
<div>
<a id="cytogeneticLocation" class="mim-anchor"></a>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: <a href="/geneMap/17/186?start=-3&limit=10&highlight=186">17p13.1</a>
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:8002615-8020342&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">17:8,002,615-8,020,342</a> </span>
</em>
</strong>
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
</span>
</p>
</div>
<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">
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</th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
<a href="/geneMap/17/186?start=-3&limit=10&highlight=186">
17p13.1
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<span class="mim-font">
?Choroidal dystrophy, central areolar 1
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
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<span class="mim-font">
<a href="/entry/215500"> 215500 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
Cone-rod dystrophy 6
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<span class="mim-font">
<a href="/entry/601777"> 601777 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
Leber congenital amaurosis 1
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<span class="mim-font">
<a href="/entry/204000"> 204000 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
Night blindness, congenital stationary, type 1I
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<span class="mim-font">
<a href="/entry/618555"> 618555 </a>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<h4>
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<strong>TEXT</strong>
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<a id="cloning" class="mim-anchor"></a>
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<strong>Cloning and Expression</strong>
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<p>Three-prime, 5-prime-cyclic guanosine monophosphate (cGMP) is the intracellular second messenger regulating phototransduction in mammals. The level of cGMP in photoreceptor cells is controlled by the cGMP-hydrolyzing enzyme cGMP phosphodiesterase and the cGMP-producing enzyme guanylate cyclase. Two major forms of cyclases are recognized, the particulate (membrane) and the soluble forms. The membrane guanylate cyclases are composed of large single subunits consisting of a ligand-binding N-terminal segment, a transmembrane domain, an internal protein kinase homology region, and a C-terminal catalytic domain. The highly homologous membrane guanylate cyclases include NPR1 (natriuretic peptide receptor A; <a href="/entry/108960">108960</a>), NPR2 (natriuretic peptide receptor B; <a href="/entry/108961">108961</a>), and NPR3 (natriuretic peptide receptor C; <a href="/entry/108962">108962</a>). <a href="#21" class="mim-tip-reference" title="Shyjan, A. W., de Sauvage, F. J., Gillett, N. A., Goeddel, D. V., Lowe, D. G. &lt;strong&gt;Molecular cloning of a retina-specific membrane guanylyl cyclase.&lt;/strong&gt; Neuron 9: 727-737, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1356371/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1356371&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0896-6273(92)90035-c&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1356371">Shyjan et al. (1992)</a> cloned a human photoreceptor guanylate cyclase, called retGC (GUCY2D). The predicted protein sequence is closely related to the other membrane guanylate cyclases, and all structural domains are well conserved. However, expressed photoreceptor guanylate cyclase is not activated by natriuretic peptides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1356371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Yang, R.-B., Foster, D. C., Garbers, D. L., Fulle, H.-J. &lt;strong&gt;Two membrane forms of guanylyl cyclase found in the eye.&lt;/strong&gt; Proc. Nat. Acad. Sci. 92: 602-606, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7831337/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7831337&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.92.2.602&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7831337">Yang et al. (1995)</a> cloned 2 guanylyl cyclases, Gucy2e and Gucyf (<a href="/entry/300041">300041</a>), from a rat eye cDNA library. These 2 rat genes are expressed in retina. The mouse and rat Gucy2e genes are homologs of human GUCY2D (<a href="#19" class="mim-tip-reference" title="Scott, A. F. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Baltimore, Md. 5/2009."None>Scott, 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7831337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The human GUCY2D protein is 87% identical to its mouse counterpart (<a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944027" 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="Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K. &lt;strong&gt;Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Biochemistry 38: 509-515, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9888789/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9888789&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1021/bi9824137&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9888789">Duda et al. (1999)</a> stated that GUCY2D, which they called rod outer segment membrane guanylate cyclase (ROS-GC1), was the original member of the subfamily of membrane guanylate cyclases with 2 Ca(2+) switches referred to as calcium-regulated modules (CRMs) and designated CRM1 and CRM2. These are separately located within the intracellular domain of the cyclase. CRM1 switches on the enzyme at nanomolar concentrations of calcium ion and is linked with phototransduction; CRM2 stimulates at micromolar calcium ion concentrations and is predicted to be linked with retinal synaptic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9888789" 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="geneStructure" class="mim-anchor"></a>
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Gene Structure</strong>
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<p><a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> determined that the human GUCY2D gene spans 16 kb and contains 20 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944027" 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="mapping" class="mim-anchor"></a>
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<strong>Mapping</strong>
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<p><a href="#14" class="mim-tip-reference" title="Oliveira, L., Miniou, P., Viegas-Pequignot, E., Rozet, J.-M., Dollfus, H., Pittler, S. J. &lt;strong&gt;Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1.&lt;/strong&gt; Genomics 22: 478-481, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7806240/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7806240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1994.1415&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7806240">Oliveira et al. (1994)</a> used PCR analysis of human-rodent somatic cell hybrids to map the GUCY2D locus to chromosome 17. The assignment was confirmed and regionalized to chromosome 17p13.1 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7806240" 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 interspecific backcross analysis, <a href="#29" class="mim-tip-reference" title="Yang, R.-B., Fulle, H.-J., Garbers, D. L. &lt;strong&gt;Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina.&lt;/strong&gt; Genomics 31: 367-372, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8838319/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8838319&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1996.0060&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8838319">Yang et al. (1996)</a> mapped the mouse Gucy2e gene to chromosome 11 in a region of syntenic homology to human 17p13 known to contain loci for autosomal dominant retinitis pigmentosa (<a href="/entry/600059">600059</a>) and Leber congenital amaurosis (<a href="/entry/204000">204000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838319" 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>Gene Function</strong>
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<p>By coimmunoprecipitation of mouse retinal extracts, <a href="#1" class="mim-tip-reference" title="Azadi, S., Molday, L. L., Molday, R. S. &lt;strong&gt;RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells.&lt;/strong&gt; Proc. Nat. Acad. Sci. 107: 21158-21163, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21078983/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21078983&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21078983[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.1010460107&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21078983">Azadi et al. (2010)</a> found that Rd3 (<a href="/entry/180040">180040</a>) bound the guanylate cyclases Gc1 and Gc2, encoded by GUCY2D and GUCY2F (<a href="/entry/300041">300041</a>), respectively. They confirmed interaction of Rd3 with Gc1 in transfected HEK293 cells. A short C-terminal segment of Gc1 was required for Rd3 binding. When expressed alone in COS-7 cells, Rd3 colocalized with the endosomal recycling marker Rab11 (see RAB11A; <a href="/entry/605570">605570</a>) in a pattern characteristic of intracellular vesicles, whereas Gc1 localized in a perinuclear distribution characteristic of endoplasmic reticulum (ER). When coexpressed, Gc1 was exported from the ER to endosomal vesicles containing Rd3 and Rab11. Retinal extracts from Rd3 mutant mice lacked Gc1 protein expression and showed reduced Gc2 protein expression compared with wildtype. The GC-activating proteins Gcap1 (GUCA1A; <a href="/entry/600364">600364</a>) and Gcap2 (GUCA1B; <a href="/entry/602275">602275</a>) also showed reduced expression in Rd3 mice, as well as mislocalization to the inner segment of photoreceptor cells. <a href="#1" class="mim-tip-reference" title="Azadi, S., Molday, L. L., Molday, R. S. &lt;strong&gt;RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells.&lt;/strong&gt; Proc. Nat. Acad. Sci. 107: 21158-21163, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21078983/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21078983&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21078983[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.1010460107&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21078983">Azadi et al. (2010)</a> proposed that RD3 may be an accessory protein required for vesicle trafficking of GCs from inner to outer segments of rod and cone cells and that it may modulate GC enzymatic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21078983" 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>Molecular Genetics</strong>
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<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
By homozygosity mapping in consanguineous families of North African origin, <a href="#2" class="mim-tip-reference" title="Camuzat, A., Dollfus, H., Rozet, J.-M., Gerber, S., Bonneau, D., Bonnemaison, M., Briard, M.-L., Dufier, J.-L., Ghazi, I., Leowski, C., Weissenbach, J., Frezal, J., Munnich, A., Kaplan, J. &lt;strong&gt;A gene for Leber&#x27;s congenital amaurosis maps to chromosome 17p.&lt;/strong&gt; Hum. Molec. Genet. 4: 1447-1452, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7581387/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7581387&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/4.8.1447&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7581387">Camuzat et al. (1995)</a> mapped a gene for Leber congenital amaurosis (LCA1; <a href="/entry/204000">204000</a>) to 17p13.1. <a href="#3" class="mim-tip-reference" title="Camuzat, A., Rozet, J.-M., Dollfus, H., Gerber, S., Perrault, I., Weissenbach, J., Munnich, A., Kaplan, J. &lt;strong&gt;Evidence of genetic heterogeneity of Leber&#x27;s congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13.&lt;/strong&gt; Hum. Genet. 97: 798-801, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8641699/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8641699&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02346192&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8641699">Camuzat et al. (1996)</a> provided evidence of genetic heterogeneity, finding that LCA1 accounted for 8/15 LCA families in their series. Based on 3 key recombinants, <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> were able to reduce the interval encompassing the LCA1 gene to a critical region of less than 1 cM. Starting from flanking markers, they ordered 12 YAC clones on 17p13.1. Of the candidate genes expressed in the retina and located on chromosome 17, none mapped to these YACs except the gene for retinal guanylate cyclase. <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> found 2 missense mutations (<a href="#0001">600179.0001</a>; <a href="#0004">600179.0004</a>) and 2 frameshift mutations (<a href="#0002">600179.0002</a>; <a href="#0003">600179.0003</a>) associated with LCA1. As specific guanylate cyclase activating proteins (GCAPs) are required for retinal guanylate cyclase activity, the study of <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> raised the question of whether some LCA cases unlinked to 17p13 could be accounted for by mutations in GCAP genes, which include the GUCA1 gene (<a href="/entry/600364">600364</a>) on 6p21.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8944027+8641699+7581387" 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="Perrault, I., Rozet, J.-M., Gerber, S., Ghazi, I., Ducroq, D., Souied, E., Leowski, C., Bonnemaison, M., Dufier, J.-L., Munnich, A., Kaplan, J. &lt;strong&gt;Spectrum of retGC1 mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Europ. J. Hum. Genet. 8: 578-582, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10951519/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10951519&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5200503&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10951519">Perrault et al. (2000)</a> screened the whole coding sequence of the RETGC1 gene in 118 patients affected with Leber congenital amaurosis. They found 22 different mutations in 24 unrelated families originating from various countries. All RETGC1 mutations consistently caused congenital cone-rod dystrophy. RETGC1 is an essential protein implicated in the phototransduction cascade, especially in the recovery of the dark state after the excitation process of photoreceptor cells by light stimulation. <a href="#17" class="mim-tip-reference" title="Perrault, I., Rozet, J.-M., Gerber, S., Ghazi, I., Ducroq, D., Souied, E., Leowski, C., Bonnemaison, M., Dufier, J.-L., Munnich, A., Kaplan, J. &lt;strong&gt;Spectrum of retGC1 mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Europ. J. Hum. Genet. 8: 578-582, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10951519/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10951519&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5200503&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10951519">Perrault et al. (2000)</a> postulated that the RETGC1 mutations hinder the restoration of the basal level of cGMP of cone and rod photoreceptor cells, leading to a situation equivalent to consistent light exposure during photoreceptor development, explaining the severity of the visual disorder at birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10951519" 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="Khan, A. O., Al-Mesfer, S., Al-Turkmani, S., Bergmann, C., Bolz, H. J. &lt;strong&gt;Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay.&lt;/strong&gt; Brit. J. Ophthal. 98: 1724-1728, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24997176/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24997176&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/bjophthalmol-2014-305122&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24997176">Khan et al. (2014)</a> performed targeted next-generation sequencing with a panel of 14 LCA genes in 23 'strictly defined' LCA patients from 19 endogamous and/or consanguineous Saudi Arabian families and identified mutations in the GUCY2D gene in 5 probands, 3 of whom had concomitant neurodevelopmental delay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997176" 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>Cone-Rod Dystrophy 6</em></strong></p><p>
Leber congenital amaurosis is inherited as an autosomal recessive. <a href="#11" class="mim-tip-reference" title="Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M. &lt;strong&gt;Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 7: 1179-1184, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9618177/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9618177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/7.7.1179&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9618177">Kelsell et al. (1998)</a> demonstrated that mutations in the GUCY2D gene are responsible also for a dominant form of cone-rod dystrophy, which they referred to as CORD6 (<a href="/entry/601777">601777</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Payne, A. M., Morris, A. G., Downes, S. M., Johnson, S., Bird, A. C., Moore, A. T., Bhattacharya, S. S., Hunt, D. M. &lt;strong&gt;Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. (Letter)&lt;/strong&gt; J. Med. Genet. 38: 611-647, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11565546/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11565546&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.38.9.611&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11565546">Payne et al. (2001)</a> studied 40 patients: 27 with autosomal dominant macular dystrophy and 13 with autosomal dominant cone or cone-rod dystrophy. Two patients were found to carry the R838C mutation (<a href="#0006">600179.0006</a>) and 1 the R838H mutation (<a href="#0008">600179.0008</a>). Combining these results with those of <a href="#11" class="mim-tip-reference" title="Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M. &lt;strong&gt;Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 7: 1179-1184, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9618177/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9618177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/7.7.1179&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9618177">Kelsell et al. (1998)</a>, <a href="#15" class="mim-tip-reference" title="Payne, A. M., Morris, A. G., Downes, S. M., Johnson, S., Bird, A. C., Moore, A. T., Bhattacharya, S. S., Hunt, D. M. &lt;strong&gt;Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. (Letter)&lt;/strong&gt; J. Med. Genet. 38: 611-647, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11565546/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11565546&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.38.9.611&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11565546">Payne et al. (2001)</a> estimated the frequency of mutations at codon 838 of the GUCY2D gene among patients with autosomal dominant macular cone or cone-rod dystrophy to be 6.7%. However, if only the 3 mutations in the 13 patients with cone or cone-rod dystrophy are considered, the estimated frequency of mutations is 23%. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11565546+9618177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a 3-generation family segregating autosomal dominant cone-rod dystrophy, <a href="#18" class="mim-tip-reference" title="Perrault, I., Rozet, J.-M., Gerber, S., Kelsell, R. E., Souied, E., Cabot, A., Hunt, D. M., Munnich, A., Kaplan, J. &lt;strong&gt;A retGC-1 mutation in autosomal dominant cone-rod dystrophy. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 63: 651-654, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9683616/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9683616&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301985&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9683616">Perrault et al. (1998)</a> identified a complex mutation event involving 3 consecutive missense mutations within a single exon (<a href="#0007">600179.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous Turkish family segregating autosomal recessive CORD mapping to chromosome 17p13.3, <a href="#25" class="mim-tip-reference" title="Ugur Iseri, S. A., Durlu, Y. K., Tolun, A. &lt;strong&gt;A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Europ. J. Hum. Genet. 18: 1121-1126, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20517349/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20517349&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20517349[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2010.81&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20517349">Ugur Iseri et al. (2010)</a> identified homozygosity for a missense mutation (<a href="#0010">600179.0010</a>) in the GUCY2D gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20517349" 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>Central Areolar Choroidal Dystrophy 1</em></strong></p><p>
In a large Irish pedigree with central areolar choroidal dystrophy mapping to chromosome 17p13 (CACD1; <a href="/entry/215500">215500</a>), <a href="#8" class="mim-tip-reference" title="Hughes, A. E., Meng, W., Lotery, A. J., Bradley, D. T. &lt;strong&gt;A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy.&lt;/strong&gt; Invest. Ophthal. Vis. Sci. 53: 4748-4753, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22695961/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22695961&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1167/iovs.12-10061&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22695961">Hughes et al. (2012)</a> identified heterozygosity for a missense mutation in the GUCY2D gene (V933A; <a href="#0011">600179.0011</a>) that segregated with disease. The authors stated that the CACD phenotype is distinctive, although it shares features in common with cone dystrophy and cone-rod dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22695961" 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>Congenital Stationary Night Blindness, Type 1I</em></strong></p><p>
In 5 patients from 4 families with congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>), <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a> identified compound heterozygosity for mutations in the GUCY2D gene (see, e.g., <a href="#0012">600179.0012</a>-<a href="#0016">600179.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Genotype/Phenotype Correlations</strong>
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<p><a href="#27" class="mim-tip-reference" title="Wilkie, S. E., Newbold, R. J., Deery, E., Walker, C. E., Stinton, I., Ramamurthy, V., Hurley, J. B., Bhattacharya, S. S., Warren, M. J., Hunt, D. M. &lt;strong&gt;Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 9: 3065-3073, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11115851/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11115851&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/9.20.3065&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11115851">Wilkie et al. (2000)</a> studied the biochemical effects of various mutations at codon 838 in RETGC1: the 3 disease-causing substitutions (R838C, <a href="#0006">600179.0006</a>; R838H, <a href="#0008">600179.0008</a> and R838S, <a href="#0005">600179.0005</a>) and 4 artificial mutations (R838A, R838E, R838L, and R838K). Assay of GCAP1-stimulated cyclase activity in vitro showed that, compared with wildtype, R838E, R838L and R838K had only low activity, whereas R838A, R838C, R838H, and R838S had activity equal to or greater than wildtype at low Ca(2+) concentrations as well as a higher apparent affinity for GCAP1 than did wildtype. The Ca(2+) sensitivity of the GCAP1 activation was also altered with marked residual activity at high Ca(2+), the effect increasing in this order: wildtype, R838C, R838H, R838A, R838S. Within the photoreceptor, this would result in a failure to inactivate cyclase activity at high physiologic Ca(2+) concentrations. Among the 3 disease-associated mutations, the effect correlated directly with disease severity. The wildtype and R838H mutant displayed a difference in pH sensitivity, with the mutant showing a higher specific activity with pH greater than 6.0. Site 838 is in the dimerization domain that forms a coiled-coil in the active protein. A computer-aided structure prediction of this region indicated that R838 in the wildtype breaks the structure at 4 helical turns, and there is an increasing tendency for the structure to continue for further turns in the order R838C; R838H,S,K; R838E; R838A; R838L. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11115851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Downes, S. M., Payne, A. M., Kelsell, R. E., Fitzke, F. W., Holder, G. E., Hunt, D. M., Moore, A. T., Bird, A. C. &lt;strong&gt;Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.&lt;/strong&gt; Arch. Ophthal. 119: 1667-1673, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11709018/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11709018&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archopht.119.11.1667&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11709018">Downes et al. (2001)</a> described the phenotype and electrophysiologic responses in 4 British families, 3 with an R838C mutation and 1 with an R838H mutation in the GUCY2D gene. Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Electrophysiologic testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. The authors concluded that the phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D was distinctive, with predominantly cone system involvement. There was some variation in severity within the 3 families with the R838C mutation. Families with the R838C or R838H mutations had a much milder phenotype than the families previously described with the E837D/R838S mutation (<a href="#0005">600179.0005</a>) in GUCY2D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W. &lt;strong&gt;Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.&lt;/strong&gt; Prog. Retin. Eye Res. 63: 69-91, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29061346/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29061346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.preteyeres.2017.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29061346">Sharon et al. (2018)</a> reviewed reported GUCY2D mutations, noting that LCA1-associated mutations were distributed throughout the protein, whereas CORD6-associated mutations were limited to the dimer domain. The authors analyzed published functional studies of GUCY2D missense mutations and found 41 such variants, including 21 associated with LCA1 and 7 with CORD6. A clear genotype-phenotype correlation was demonstrated, in which LCA1-associated mutations showed either reduced ability or complete inability to synthesize cGMP from GTP, whereas CORD6-associated mutations were functional, but shifted the Ca(2+) sensitivity of the Gc1-GCAP complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29061346" 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="allelicVariants" class="mim-anchor"></a>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>16 Selected Examples</a>):</strong>
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<a href="/allelicVariants/600179" class="btn btn-default" role="button"> Table View </a>
&nbsp;&nbsp;<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600179[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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<a id="0001" class="mim-anchor"></a>
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<strong>.0001&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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GUCY2D, PHE565SER
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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">&#x25cf;</span> rs61749755 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749755;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/rs61749755?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61749755" 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=rs61749755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
<span class="mim-text-font">
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009944 OR RCV000084839 OR RCV005053885" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009944, RCV000084839, RCV005053885" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009944...</a>
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<span class="mim-text-font">
<p>In all sibs with Leber congenital amaurosis (LCA1; <a href="/entry/204000">204000</a>) in 2 consanguineous Arab-Algerian families, <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> found homozygosity for a T-to-C transition in exon 8 at nucleotide 1767 of the GUC2D gene. The nucleotide change converted phenylalanine to serine in the protein. The substitution of an aromatic nonpolar amino acid by an uncharged polar amino acid within the kinase-like domain markedly altered the hydrophobicity of the protein and was expected to affect its stability severely. <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> reported the predicted change at amino acid 589 (F589S), but <a href="#5" class="mim-tip-reference" title="Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K. &lt;strong&gt;Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Biochemistry 38: 509-515, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9888789/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9888789&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1021/bi9824137&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9888789">Duda et al. (1999)</a> stated that the correct position is 565. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8944027+9888789" 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="Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K. &lt;strong&gt;Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Biochemistry 38: 509-515, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9888789/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9888789&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1021/bi9824137&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9888789">Duda et al. (1999)</a> showed that the bovine F514S mutation, which corresponds to the human F565S mutation, severely damages the intrinsic cyclase activity of ROS-GC1 and inactivates its CRM1 switch but does not affect the CRM2 switch. In addition, on the basis of the established modulatory features of ROS-GC1, <a href="#5" class="mim-tip-reference" title="Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K. &lt;strong&gt;Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Biochemistry 38: 509-515, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9888789/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9888789&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1021/bi9824137&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9888789">Duda et al. (1999)</a> predicted that in 2 other forms of Leber congenital amaurosis involving deletion of nucleotide 460C (<a href="#0002">600179.0002</a>) or 693C (<a href="#0003">600179.0003</a>), there is a frameshift in the GUCY2D gene that results in nonexpression of the cyclase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9888789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Yzer, S., Leroy, B. P., De Baere, E., de Ravel, T. J., Zonneveld, M. N., Voesenek, K., Kellner, U., Martinez Ciriano, J. P., de Faber, J.-T. H. N., Rohrschneider, K., Roepman, R., den Hollander, A. I., Cruysberg, J. R., Meire, F., Casteels, I., van Moll-Ramirez, N. G., Allikmets, R., van den Born, L. I., Cremers, F. P. M. &lt;strong&gt;Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis.&lt;/strong&gt; Invest. Ophthal. Vis. Sci. 47: 1167-1176, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16505055/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16505055&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1167/iovs.05-0848&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16505055">Yzer et al. (2006)</a> reported a 25-year-old woman with LCA (patient 22597) who had 2 affected sibs; she was homozygous for the F565S mutation (c.1694T-C) in GUCY2D. An unrelated 1-year-old girl with LCA (patient 441) was compound heterozygous for F565S and an R768W substitution in GUCY2D (<a href="#0012">600179.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W. &lt;strong&gt;Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.&lt;/strong&gt; Prog. Retin. Eye Res. 63: 69-91, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29061346/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29061346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.preteyeres.2017.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29061346">Sharon et al. (2018)</a> noted that the F565S mutation arose from a c.1694T-C transition (c.1694T-C, NM_000180.3) in exon 8 of GUCY2D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29061346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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GUCY2D, 1-BP DEL, 460C
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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">&#x25cf;</span> rs61749670 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749670;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/rs61749670?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61749670" 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=rs61749670" 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=RCV000009945 OR RCV000084897 OR RCV000693446 OR RCV001003037 OR RCV002498447 OR RCV005053901" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009945, RCV000084897, RCV000693446, RCV001003037, RCV002498447, RCV005053901" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009945...</a>
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<p>In a Jewish Sephardi family of Tunisian origin, <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> found that members with Leber congenital amaurosis (<a href="/entry/204000">204000</a>) were homozygous for a 1-bp deletion (460delC) in exon 2 at nucleotide 460 of GUC2D that modified the downstream amino acid sequence, abolished a SmaI restriction site, and resulted in a premature translation termination at codon 165. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944027" 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&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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GUCY2D, 1-BP DEL, 693C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749671;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=rs61749671" 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=rs61749671" 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=RCV000009946 OR RCV000084903" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009946, RCV000084903" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009946...</a>
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<p>In members of an Arab family of Tunisian origin affected with Leber congenital amaurosis (<a href="/entry/204000">204000</a>), <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> observed a homozygous 1-bp deletion in exon 2 at nucleotide 693 (693delC) of GUC2D that modified the downstream amino acid sequence, created a BspMI restriction site, and resulted in a premature translation termination at codon 215. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944027" 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&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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GUCY2D, ALA52SER
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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">&#x25cf;</span> rs61749665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749665;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/rs61749665?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61749665" 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=rs61749665" 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=RCV000009947 OR RCV000078318 OR RCV000084835 OR RCV001518075 OR RCV002225071 OR RCV002490349 OR RCV005053886" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009947, RCV000078318, RCV000084835, RCV001518075, RCV002225071, RCV002490349, RCV005053886" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009947...</a>
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<p>In all sibs with Leber congenital amaurosis (<a href="/entry/204000">204000</a>) in a consanguineous Arab Tunisian family, <a href="#16" class="mim-tip-reference" title="Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J. &lt;strong&gt;Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Nature Genet. 14: 461-464, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8944027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8944027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1296-461&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8944027">Perrault et al. (1996)</a> found homozygosity for a G-to-T transversion at nucleotide 227 of GUC2D converting an alanine into a serine (A52S). Heterozygosity for the same mutation was detected in affected members of a family of Basque ancestry. As the same base change was detected in 2 of 100 controls, it was difficult to decide whether this was a disease-causing mutation or a rare polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005&nbsp;CONE-ROD DYSTROPHY 6</strong>
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GUCY2D, GLU837ASP AND ARG838SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933695 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933695;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=rs28933695" 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=rs28933695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">&#x25cf;</span> rs61750172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750172;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/rs61750172?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750172" 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=rs61750172" 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=RCV000009948 OR RCV000009950 OR RCV000084860 OR RCV000084861 OR RCV001854486" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009948, RCV000009950, RCV000084860, RCV000084861, RCV001854486" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009948...</a>
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<p>In a 4-generation British family with cone-rod dystrophy (CORD6; <a href="/entry/601777">601777</a>), <a href="#10" class="mim-tip-reference" title="Kelsell, R. E., Evans, K., Gregory, C. Y., Moore, A. T., Bird, A. C., Hunt, D. M. &lt;strong&gt;Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p.&lt;/strong&gt; Hum. Molec. Genet. 6: 597-600, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9097965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9097965&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.4.597&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9097965">Kelsell et al. (1997)</a> showed linkage between the disorder and 17p13-p12. Cone-rod dystrophy in this family displayed an early onset, with loss of central vision reported before 7 years of age and peripheral field loss by the fourth decade. A notable feature was marked photophobia, particularly when dark-adapted. Funduscopy showed a 'bull's eye' maculopathy early in the disease, with later involvement of the peripheral retina. Electroretinography showed no detectable cone responses early in the disease, with progressive abnormality of rod responses appearing later. <a href="#11" class="mim-tip-reference" title="Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M. &lt;strong&gt;Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 7: 1179-1184, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9618177/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9618177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/7.7.1179&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9618177">Kelsell et al. (1998)</a> studied the GUC2D gene because it maps to the same chromosomal area. Direct sequence analysis of all 18 coding exons of the gene demonstrated a heterozygous alteration in exon 13: 2584G-C, predicted to cause a glu837-to-asp (E837D) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9618177+9097965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gregory-Evans, K., Kelsell, R. E., Gregory-Evans, C. Y., Downes, S. M., Fitzke, F. W., Holder, G. E., Simunovic, M., Mollon, J. D., Taylor, R., Huntt, D. M., Bird, A. C., Moore, A. T. &lt;strong&gt;Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.&lt;/strong&gt; Ophthalmology 107: 55-61, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10647719/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10647719&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0161-6420(99)00038-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10647719">Gregory-Evans et al. (2000)</a> stated that further analysis of the family originally studied by <a href="#10" class="mim-tip-reference" title="Kelsell, R. E., Evans, K., Gregory, C. Y., Moore, A. T., Bird, A. C., Hunt, D. M. &lt;strong&gt;Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p.&lt;/strong&gt; Hum. Molec. Genet. 6: 597-600, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9097965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9097965&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.4.597&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9097965">Kelsell et al. (1997)</a> led to a reappraisal of the mutation, redefined as glu837 to asp/arg838 to ser. They described the clinical features in this family (see <a href="/entry/601777">601777</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9097965+10647719" 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&nbsp;CONE-ROD DYSTROPHY 6</strong>
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GUCY2D, ARG838CYS
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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">&#x25cf;</span> rs61750172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750172;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/rs61750172?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750172" 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=rs61750172" 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=RCV000009949 OR RCV000009950 OR RCV000084862 OR RCV001003042 OR RCV001065465 OR RCV001074299 OR RCV001197374 OR RCV001376215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009949, RCV000009950, RCV000084862, RCV001003042, RCV001065465, RCV001074299, RCV001197374, RCV001376215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009949...</a>
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<p><a href="#11" class="mim-tip-reference" title="Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M. &lt;strong&gt;Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 7: 1179-1184, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9618177/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9618177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/7.7.1179&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9618177">Kelsell et al. (1998)</a> found another heterozygous mutation of the GUC2D gene in a family with cone-rod dystrophy (CORD6; <a href="/entry/601777">601777</a>) with features somewhat different from that of the original CORD6 family described in <a href="#0005">600179.0005</a>. In 3 families carrying this second mutation (arg838 to cys; R838C), affected individuals, although aware of poor vision in bright light from an early age, suffered loss of central vision in the late second or third decade, later than was found in the original family with the E837D mutation. The fundus appearance of affected members of these 3 families was, however, very similar to that of the original family. Electrophysiologic testing revealed marked loss of photopic function by the mid-teens, with scotopic function becoming compromised later. Genealogic studies failed to show a relationship between the 3 families. The R838C amino acid substitution resulted from a C-to-T transition at nucleotide 2585. Alignment of the portion of membrane-bound guanylate cyclases in this domain, represented by codons 809 to 871, showed that both glu837 and arg838 are fully conserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618177" 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 38 affected members of a large multigenerational family from eastern Tennessee with autosomal dominant progressive cone dystrophy, originally described by <a href="#22" class="mim-tip-reference" title="Small, K. W., Gehrs, K. &lt;strong&gt;Clinical study of a large family with autosomal dominant progressive cone degeneration.&lt;/strong&gt; Am. J. Ophthal. 121: 1-12, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8554074/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8554074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0002-9394(14)70528-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8554074">Small and Gehrs (1996)</a>, <a href="#24" class="mim-tip-reference" title="Udar, N., Yelchits, S., Chalukya, M., Yellore, V., Nusinowitz, S., Silva-Garcia, R., Vrabec, T., Maumenee, I. H., Donoso, L., Small, K. W. &lt;strong&gt;Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.&lt;/strong&gt; Hum. Mutat. 21: 170-171, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12552567/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12552567&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.9109&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12552567">Udar et al. (2003)</a> identified the R838C mutation in the GUCY2D gene. The mutation was also detected in 2 unaffected family members, but was not found in 22 additional unaffected family members or 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12552567+8554074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007&nbsp;CONE-ROD DYSTROPHY 6</strong>
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GUCY2D, GLU837ASP, ARG838CYS, AND THR839MET
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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">&#x25cf;</span> rs61750172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750172;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/rs61750172?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750172" 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=rs61750172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">&#x25cf;</span> rs61750174 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750174;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/rs61750174?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750174" 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=rs61750174" 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=RCV000009948 OR RCV000009949 OR RCV000009950 OR RCV000084860 OR RCV000084862 OR RCV000084864 OR RCV001003042 OR RCV001065465 OR RCV001074299 OR RCV001197374 OR RCV001239266 OR RCV001376215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009948, RCV000009949, RCV000009950, RCV000084860, RCV000084862, RCV000084864, RCV001003042, RCV001065465, RCV001074299, RCV001197374, RCV001239266, RCV001376215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009948...</a>
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<p>In 6 affected members from a 3-generation family with autosomal dominant cone-rod dystrophy (CORD6; <a href="/entry/601777">601777</a>), <a href="#18" class="mim-tip-reference" title="Perrault, I., Rozet, J.-M., Gerber, S., Kelsell, R. E., Souied, E., Cabot, A., Hunt, D. M., Munnich, A., Kaplan, J. &lt;strong&gt;A retGC-1 mutation in autosomal dominant cone-rod dystrophy. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 63: 651-654, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9683616/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9683616&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301985&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9683616">Perrault et al. (1998)</a> identified heterozygosity for a complex mutational event involving 3 consecutive missense mutations in exon 13: (1) a G-to-C transversion at nucleotide 2584, changing a glutamate to an aspartate at codon 837 (E837D); (2) a C-to-T transition at nucleotide 2585, changing an arginine to a cysteine at codon 838 (R838C); and (3) a C-to-T transition at nucleotide 2589, changing a threonine to a methionine at codon 839 (T839M). This triple mutation was considered to represent a gene conversion event. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008&nbsp;CONE-ROD DYSTROPHY 6</strong>
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GUCY2D, ARG838HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750173 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750173;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=rs61750173" 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=rs61750173" 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=RCV000009951 OR RCV000084863 OR RCV000504851 OR RCV000787614 OR RCV001003043 OR RCV001228516 OR RCV001271114 OR RCV001723556 OR RCV003324497" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009951, RCV000084863, RCV000504851, RCV000787614, RCV001003043, RCV001228516, RCV001271114, RCV001723556, RCV003324497" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009951...</a>
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<p>In a patient with cone-rod dystrophy-6 (CORD6; <a href="/entry/601777">601777</a>), <a href="#26" class="mim-tip-reference" title="Weigell-Weber, M., Fokstuen, S., Torok, B., Niemeyer, G., Schinzel, A., Hergersberg, M. &lt;strong&gt;Codons 837 and 838 in the retinal guanylate cyclase gene on chromosome 17p: hot spots for mutations in autosomal dominant cone-rod dystrophy?&lt;/strong&gt; Arch. Ophthal. 118: 300 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10676808/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10676808&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archopht.118.2.300&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10676808">Weigell-Weber et al. (2000)</a> detected a G-to-A transition of the GCGC stretch at position 2586 in exon 13 of the GUCY2D gene, resulting in a conservative arg838-to-his (R838H) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10676808" 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 8 affected members of a Caucasian American family with cone dystrophy, <a href="#24" class="mim-tip-reference" title="Udar, N., Yelchits, S., Chalukya, M., Yellore, V., Nusinowitz, S., Silva-Garcia, R., Vrabec, T., Maumenee, I. H., Donoso, L., Small, K. W. &lt;strong&gt;Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.&lt;/strong&gt; Hum. Mutat. 21: 170-171, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12552567/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12552567&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.9109&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12552567">Udar et al. (2003)</a> identified the R838H mutation in the GUCY2D gene. The mutation was not found in 5 unaffected family members or 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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GUCY2D, 1-BP DEL, 2943G
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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">&#x25cf;</span> rs61750185 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750185;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/rs61750185?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750185" 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=rs61750185" 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=RCV000084877 OR RCV001250850 OR RCV001381496 OR RCV004748576 OR RCV004815026 OR RCV004815027 OR RCV005053898" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000084877, RCV001250850, RCV001381496, RCV004748576, RCV004815026, RCV004815027, RCV005053898" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000084877...</a>
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<p><a href="#7" class="mim-tip-reference" title="Hanein, S., Perrault, I., Olsen, P., Lopponen, T., Hietala, M., Gerber, S., Jeanpierre, M., Barbet, F., Ducroq, D., Hakiki, S., Munnich, A., Rozet, J.-M., Kaplan, J. &lt;strong&gt;Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin.&lt;/strong&gt; Hum. Mutat. 20: 322-323, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12325031/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12325031&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.9067&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12325031">Hanein et al. (2002)</a> identified a homozygous 2943G deletion (2943delG) in the GUCY2D gene in 3 unrelated and nonconsanguineous Leber congenital amaurosis (<a href="/entry/204000">204000</a>) families of Finnish origin, suggesting a founder effect. No linkage disequilibrium was found using polymorphic markers flanking the GUCY2D gene, supporting the view that the mutation is very ancient. Haplotype studies and Bayesian calculation pointed the founder mutation to 150 generations (i.e., 3,000 years ago). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12325031" 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="0010" class="mim-anchor"></a>
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<strong>.0010&nbsp;CONE-ROD DYSTROPHY 6</strong>
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GUCY2D, ILE949THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606857 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606857;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=rs267606857" 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=rs267606857" 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=RCV000009953" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009953" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009953</a>
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<p>In 6 affected members of a consanguineous Turkish family segregating autosomal recessive cone-rod dystrophy-6 (CORD6; <a href="/entry/601777">601777</a>), <a href="#25" class="mim-tip-reference" title="Ugur Iseri, S. A., Durlu, Y. K., Tolun, A. &lt;strong&gt;A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Europ. J. Hum. Genet. 18: 1121-1126, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20517349/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20517349&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20517349[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2010.81&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20517349">Ugur Iseri et al. (2010)</a> identified homozygosity for a 2846T-C transition in exon 15 of the GUCY2D gene, resulting in an ile949-to-thr (I949T) substitution at a highly conserved residue in the catalytic domain. The mutation was not detected in 186 control chromosomes. <a href="#25" class="mim-tip-reference" title="Ugur Iseri, S. A., Durlu, Y. K., Tolun, A. &lt;strong&gt;A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber&#x27;s congenital amaurosis.&lt;/strong&gt; Europ. J. Hum. Genet. 18: 1121-1126, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20517349/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20517349&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20517349[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2010.81&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20517349">Ugur Iseri et al. (2010)</a> predicted that substitution of hydrophobic isoleucine with polar threonine in this region would interfere with proper folding of the helical segment and affect function of the catalytic domain, and they proposed that the I949T mutation does not abolish but only decreases enzymatic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20517349" 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&nbsp;CENTRAL AREOLAR CHOROIDAL DYSTROPHY 1 (1 family)</strong>
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GUCY2D, VAL933ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1567961904 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567961904;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=rs1567961904" 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=rs1567961904" 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=RCV000755725" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000755725" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000755725</a>
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<p>In a large Irish pedigree with central areolar choroidal dystrophy-1 (CACD1; <a href="/entry/215500">215500</a>), originally reported by <a href="#13" class="mim-tip-reference" title="Lotery, A. J., Ennis, K. T., Silvestri, G., Nicholl, S., McGibbon, D., Collins, A. D., Hughes, A. E. &lt;strong&gt;Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.&lt;/strong&gt; Hum. Molec. Genet. 5: 705-708, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8733141/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8733141&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.5.705&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8733141">Lotery et al. (1996)</a>, <a href="#8" class="mim-tip-reference" title="Hughes, A. E., Meng, W., Lotery, A. J., Bradley, D. T. &lt;strong&gt;A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy.&lt;/strong&gt; Invest. Ophthal. Vis. Sci. 53: 4748-4753, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22695961/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22695961&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1167/iovs.12-10061&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22695961">Hughes et al. (2012)</a> identified heterozygosity for a point mutation (chr17.7,918,674T-C, GRCh37) in exon 15 of the GUCY2D gene, resulting in a val933-to-ala (V933A) substitution within the catalytic domain. The mutation segregated with disease and was not found in 7 control samples or in the 1000 Genomes Project database. No functional studies were performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8733141+22695961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0012" class="mim-anchor"></a>
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<strong>.0012&nbsp;LEBER CONGENITAL AMAUROSIS 1</strong>
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NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I, INCLUDED
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GUCY2D, ARG768TRP
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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">&#x25cf;</span> rs61750168 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750168;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/rs61750168?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61750168" 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=rs61750168" 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=RCV000084856 OR RCV000543628 OR RCV000787613 OR RCV000850093 OR RCV000850094 OR RCV001075745 OR RCV002477250 OR RCV004748575 OR RCV005053896" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000084856, RCV000543628, RCV000787613, RCV000850093, RCV000850094, RCV001075745, RCV002477250, RCV004748575, RCV005053896" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000084856...</a>
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<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
In 3 patients (designated 20955, 21557, and 22018) with Leber congenital amaurosis (LCA1; <a href="/entry/204000">204000</a>) <a href="#30" class="mim-tip-reference" title="Yzer, S., Leroy, B. P., De Baere, E., de Ravel, T. J., Zonneveld, M. N., Voesenek, K., Kellner, U., Martinez Ciriano, J. P., de Faber, J.-T. H. N., Rohrschneider, K., Roepman, R., den Hollander, A. I., Cruysberg, J. R., Meire, F., Casteels, I., van Moll-Ramirez, N. G., Allikmets, R., van den Born, L. I., Cremers, F. P. M. &lt;strong&gt;Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis.&lt;/strong&gt; Invest. Ophthal. Vis. Sci. 47: 1167-1176, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16505055/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16505055&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1167/iovs.05-0848&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16505055">Yzer et al. (2006)</a> identified homozygosity for a c.2302C-T transition in exon 12 of the GUCY2D gene, resulting in an arg768-to-trp (R768W) substitution. Two more LCA patients were compound heterozygous for R768W and another missense mutation in GUCY2D, including the F565S mutation (<a href="#0001">600179.0001</a>) in 1 of them (patient 441). The 3 homozygous patients were severely affected, with no light perception upon initial examination in infancy and no signs of improvement later in life. The authors noted that the 8 R768W alleles were Dutch or Belgian in origin, suggestive of a founder effect in the northwestern region of Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Jacobson, S. G., Cideciyan, A. V., Peshenko, I. V., Sumaroka, A., Olshevskaya, E. V., Cao, L., Schwartz, S. B., Roman, A. J., Olivares, M. B., Sadigh, S., Yau, K.-W., Heon, E., Stone, E. M., Dizhoor, A. M. &lt;strong&gt;Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants.&lt;/strong&gt; Hum. Molec. Genet. 22: 168-183, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23035049/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23035049&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23035049[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds421&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23035049">Jacobson et al. (2013)</a> reported 10 patients with LCA who carried the R768W mutation in the GUCY2D gene, 2 in homozygosity and 8 in compound heterozygosity. One of the compound heterozygotes (patient 2) also carried the Q545X mutation (<a href="#0015">600179.0015</a>). The patients were all of British/Irish or Scandinavian ancestry, except for 1 Greek homozygote. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23035049" 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>Night Blindness, Congenital Stationary, Type1I</em></strong></p><p>
In a brother and sister (patients 1 and 4), ages 17 years and 13 years, respectively, with type 1I congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>), <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a> identified compound heterozygosity for missense mutations in the GUCY2D gene: an arg768-to-trp (R768W) substitution, and a leu911-to-phe (L911F; <a href="#0013">600179.0013</a>) substitution. The boy had night blindness from infancy, whereas his sister became symptomatic at age 12 years; both had normal visual acuity. Also, in an unrelated 53-year-old woman (patient 5) with CSNB, the authors identified compound heterozygosity for the R768W mutation and an arg761-to-trp (R761W; <a href="#0014">600179.0014</a>) substitution in GUCY2D. In addition to night blindness, the older woman exhibited constricted visual fields and bone spicule-like pigmentation in the retinal periphery, but visual acuity remained intact. <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a> reported that the R761W variant was present in the ExAC database, in heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W. &lt;strong&gt;Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.&lt;/strong&gt; Prog. Retin. Eye Res. 63: 69-91, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29061346/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29061346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.preteyeres.2017.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29061346">Sharon et al. (2018)</a> noted that the R768W mutation arose from a c.2302C-T transition (c.2302C-T, NM_000180.3) in exon 12 of GUCY2D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29061346" 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>For discussion of the leu911-to-phe (L911F) substitution that was found in compound heterozygous state in sibs (patients 1 and 4) with congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>) by <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a>, see <a href="#0012">600179.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" 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>For discussion of the arg761-to-trp (R761W) substitution that was found in compound heterozygous state in a 52-year-old woman (patient 5) with congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>) by <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a>, see <a href="#0012">600179.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015&nbsp;LEBER CONGENITAL AMAUROSIS 1</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">rs1290420698 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1290420698;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=rs1290420698" 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=rs1290420698" 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=RCV000850097 OR RCV000850098 OR RCV003768615 OR RCV004726700 OR RCV005053957" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000850097, RCV000850098, RCV003768615, RCV004726700, RCV005053957" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000850097...</a>
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<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
<a href="#9" class="mim-tip-reference" title="Jacobson, S. G., Cideciyan, A. V., Peshenko, I. V., Sumaroka, A., Olshevskaya, E. V., Cao, L., Schwartz, S. B., Roman, A. J., Olivares, M. B., Sadigh, S., Yau, K.-W., Heon, E., Stone, E. M., Dizhoor, A. M. &lt;strong&gt;Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants.&lt;/strong&gt; Hum. Molec. Genet. 22: 168-183, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23035049/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23035049&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23035049[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds421&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23035049">Jacobson et al. (2013)</a> studied a 7-year-old boy (patient 2) with Leber congenital amaurosis-1 (LCA1; <a href="/entry/204000">204000</a>), who was compound heterozygous for the R768W mutation in the GUCY2D gene (<a href="#0012">600179.0012</a>) and a gln545-to-ter (Q545X) substitution. The authors noted that the Q545X mutation truncates a major portion of the intracellular segment of the cyclase, thus eliminating its entire function. Electroretinography (ERG) in the proband showed no detectable cone function but considerable retention of rod function. In addition to LCA, the boy had been diagnosed with mild autism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23035049" 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>Night Blindness, Congenital Stationary, Type1I</em></strong></p><p>
In a 15-year-old boy (patient 2) with type 1I congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>), <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a> identified compound heterozygosity for a nonsense mutation (gln545-to-ter; Q545X) and a missense mutation (arg83-to-cys; R83C; <a href="#0016">600179.0016</a>). <a href="#20" class="mim-tip-reference" title="Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W. &lt;strong&gt;Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.&lt;/strong&gt; Prog. Retin. Eye Res. 63: 69-91, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29061346/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29061346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.preteyeres.2017.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29061346">Sharon et al. (2018)</a> noted that the Q545X mutation arose from a c.1633C-T transition (c.1633C-T, NM_000180.3) in exon 7 of GUCY2D. The proband, who had lifelong night blindness, showed no rod response on ERG, but had nearly normal 30-Hz flicker cone responses with 20/20 visual acuity. ERG amplitudes decreased over 5 years of follow-up and he developed peripheral visual field defects, but visual acuity remained stable. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29061346+29559409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016&nbsp;NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I</strong>
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GUCY2D, ARG83CYS
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000850099" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000850099" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000850099</a>
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<p>For discussion of the arg83-to-cys (R83C) substitution that was found in compound heterozygous state in a 15-year-old boy (patient 2) with congenital stationary night blindness (CSNB1I; <a href="/entry/618555">618555</a>) by <a href="#23" class="mim-tip-reference" title="Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V. &lt;strong&gt;Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.&lt;/strong&gt; Am. J. Ophthal. 190: 58-68, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29559409/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29559409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajo.2018.03.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29559409">Stunkel et al. (2018)</a>, see <a href="#0015">600179.0015</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Azadi2010" class="mim-anchor"></a>
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Azadi, S., Molday, L. L., Molday, R. S.
<strong>RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21078983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21078983</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21078983[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=21078983" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.1010460107" target="_blank">Full Text</a>]
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<a id="Camuzat1995" class="mim-anchor"></a>
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Camuzat, A., Dollfus, H., Rozet, J.-M., Gerber, S., Bonneau, D., Bonnemaison, M., Briard, M.-L., Dufier, J.-L., Ghazi, I., Leowski, C., Weissenbach, J., Frezal, J., Munnich, A., Kaplan, J.
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Hum. Molec. Genet. 4: 1447-1452, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581387</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/4.8.1447" target="_blank">Full Text</a>]
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<a id="Camuzat1996" class="mim-anchor"></a>
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Camuzat, A., Rozet, J.-M., Dollfus, H., Gerber, S., Perrault, I., Weissenbach, J., Munnich, A., Kaplan, J.
<strong>Evidence of genetic heterogeneity of Leber's congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13.</strong>
Hum. Genet. 97: 798-801, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8641699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8641699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8641699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF02346192" target="_blank">Full Text</a>]
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Downes, S. M., Payne, A. M., Kelsell, R. E., Fitzke, F. W., Holder, G. E., Hunt, D. M., Moore, A. T., Bird, A. C.
<strong>Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.</strong>
Arch. Ophthal. 119: 1667-1673, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archopht.119.11.1667" target="_blank">Full Text</a>]
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Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K.
<strong>Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber's congenital amaurosis.</strong>
Biochemistry 38: 509-515, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9888789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9888789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9888789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1021/bi9824137" target="_blank">Full Text</a>]
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Gregory-Evans, K., Kelsell, R. E., Gregory-Evans, C. Y., Downes, S. M., Fitzke, F. W., Holder, G. E., Simunovic, M., Mollon, J. D., Taylor, R., Huntt, D. M., Bird, A. C., Moore, A. T.
<strong>Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.</strong>
Ophthalmology 107: 55-61, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10647719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10647719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10647719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0161-6420(99)00038-x" target="_blank">Full Text</a>]
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<a id="Hanein2002" class="mim-anchor"></a>
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Hanein, S., Perrault, I., Olsen, P., Lopponen, T., Hietala, M., Gerber, S., Jeanpierre, M., Barbet, F., Ducroq, D., Hakiki, S., Munnich, A., Rozet, J.-M., Kaplan, J.
<strong>Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin.</strong>
Hum. Mutat. 20: 322-323, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12325031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12325031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12325031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.9067" target="_blank">Full Text</a>]
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<a id="Hughes2012" class="mim-anchor"></a>
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Hughes, A. E., Meng, W., Lotery, A. J., Bradley, D. T.
<strong>A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy.</strong>
Invest. Ophthal. Vis. Sci. 53: 4748-4753, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22695961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22695961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22695961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1167/iovs.12-10061" target="_blank">Full Text</a>]
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<a id="Jacobson2013" class="mim-anchor"></a>
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Jacobson, S. G., Cideciyan, A. V., Peshenko, I. V., Sumaroka, A., Olshevskaya, E. V., Cao, L., Schwartz, S. B., Roman, A. J., Olivares, M. B., Sadigh, S., Yau, K.-W., Heon, E., Stone, E. M., Dizhoor, A. M.
<strong>Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants.</strong>
Hum. Molec. Genet. 22: 168-183, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23035049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23035049</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23035049[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=23035049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/dds421" target="_blank">Full Text</a>]
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<a id="Kelsell1997" class="mim-anchor"></a>
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Kelsell, R. E., Evans, K., Gregory, C. Y., Moore, A. T., Bird, A. C., Hunt, D. M.
<strong>Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p.</strong>
Hum. Molec. Genet. 6: 597-600, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/6.4.597" target="_blank">Full Text</a>]
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<a id="Kelsell1998" class="mim-anchor"></a>
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Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M.
<strong>Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.</strong>
Hum. Molec. Genet. 7: 1179-1184, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618177</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/7.7.1179" target="_blank">Full Text</a>]
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<a id="Khan2014" class="mim-anchor"></a>
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Khan, A. O., Al-Mesfer, S., Al-Turkmani, S., Bergmann, C., Bolz, H. J.
<strong>Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay.</strong>
Brit. J. Ophthal. 98: 1724-1728, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/bjophthalmol-2014-305122" target="_blank">Full Text</a>]
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<a id="Lotery1996" class="mim-anchor"></a>
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Lotery, A. J., Ennis, K. T., Silvestri, G., Nicholl, S., McGibbon, D., Collins, A. D., Hughes, A. E.
<strong>Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.</strong>
Hum. Molec. Genet. 5: 705-708, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8733141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8733141</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8733141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/5.5.705" target="_blank">Full Text</a>]
</p>
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<li>
<a id="14" class="mim-anchor"></a>
<a id="Oliveira1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Oliveira, L., Miniou, P., Viegas-Pequignot, E., Rozet, J.-M., Dollfus, H., Pittler, S. J.
<strong>Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1.</strong>
Genomics 22: 478-481, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7806240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7806240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7806240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/geno.1994.1415" target="_blank">Full Text</a>]
</p>
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<a id="15" class="mim-anchor"></a>
<a id="Payne2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Payne, A. M., Morris, A. G., Downes, S. M., Johnson, S., Bird, A. C., Moore, A. T., Bhattacharya, S. S., Hunt, D. M.
<strong>Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. (Letter)</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11565546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.38.9.611" target="_blank">Full Text</a>]
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<a id="Perrault1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J.
<strong>Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis.</strong>
Nature Genet. 14: 461-464, 1996.
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[<a href="https://doi.org/10.1038/ng1296-461" target="_blank">Full Text</a>]
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<a id="17" class="mim-anchor"></a>
<a id="Perrault2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Perrault, I., Rozet, J.-M., Gerber, S., Ghazi, I., Ducroq, D., Souied, E., Leowski, C., Bonnemaison, M., Dufier, J.-L., Munnich, A., Kaplan, J.
<strong>Spectrum of retGC1 mutations in Leber's congenital amaurosis.</strong>
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[<a href="https://doi.org/10.1038/sj.ejhg.5200503" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
<a id="Perrault1998" class="mim-anchor"></a>
<div class="">
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Perrault, I., Rozet, J.-M., Gerber, S., Kelsell, R. E., Souied, E., Cabot, A., Hunt, D. M., Munnich, A., Kaplan, J.
<strong>A retGC-1 mutation in autosomal dominant cone-rod dystrophy. (Letter)</strong>
Am. J. Hum. Genet. 63: 651-654, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/301985" target="_blank">Full Text</a>]
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<a id="19" class="mim-anchor"></a>
<a id="Scott2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scott, A. F.
<strong>Personal Communication.</strong>
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<p class="mim-text-font">
Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W.
<strong>Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29061346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29061346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29061346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.preteyeres.2017.10.003" target="_blank">Full Text</a>]
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<a id="Shyjan1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shyjan, A. W., de Sauvage, F. J., Gillett, N. A., Goeddel, D. V., Lowe, D. G.
<strong>Molecular cloning of a retina-specific membrane guanylyl cyclase.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1356371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1356371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1356371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0896-6273(92)90035-c" target="_blank">Full Text</a>]
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<a id="Small1996" class="mim-anchor"></a>
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Small, K. W., Gehrs, K.
<strong>Clinical study of a large family with autosomal dominant progressive cone degeneration.</strong>
Am. J. Ophthal. 121: 1-12, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0002-9394(14)70528-8" target="_blank">Full Text</a>]
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<a id="Stunkel2018" class="mim-anchor"></a>
<div class="">
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Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V.
<strong>Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.</strong>
Am. J. Ophthal. 190: 58-68, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29559409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29559409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29559409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajo.2018.03.021" target="_blank">Full Text</a>]
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<a id="24" class="mim-anchor"></a>
<a id="Udar2003" class="mim-anchor"></a>
<div class="">
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Udar, N., Yelchits, S., Chalukya, M., Yellore, V., Nusinowitz, S., Silva-Garcia, R., Vrabec, T., Maumenee, I. H., Donoso, L., Small, K. W.
<strong>Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.</strong>
Hum. Mutat. 21: 170-171, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.9109" target="_blank">Full Text</a>]
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<a id="25" class="mim-anchor"></a>
<a id="Ugur Iseri2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ugur Iseri, S. A., Durlu, Y. K., Tolun, A.
<strong>A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis.</strong>
Europ. J. Hum. Genet. 18: 1121-1126, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20517349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20517349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20517349[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=20517349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ejhg.2010.81" target="_blank">Full Text</a>]
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<a id="Weigell-Weber2000" class="mim-anchor"></a>
<div class="">
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Weigell-Weber, M., Fokstuen, S., Torok, B., Niemeyer, G., Schinzel, A., Hergersberg, M.
<strong>Codons 837 and 838 in the retinal guanylate cyclase gene on chromosome 17p: hot spots for mutations in autosomal dominant cone-rod dystrophy?</strong>
Arch. Ophthal. 118: 300 only, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10676808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10676808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10676808" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archopht.118.2.300" target="_blank">Full Text</a>]
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<a id="Wilkie2000" class="mim-anchor"></a>
<div class="">
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Wilkie, S. E., Newbold, R. J., Deery, E., Walker, C. E., Stinton, I., Ramamurthy, V., Hurley, J. B., Bhattacharya, S. S., Warren, M. J., Hunt, D. M.
<strong>Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy.</strong>
Hum. Molec. Genet. 9: 3065-3073, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11115851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11115851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11115851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/9.20.3065" target="_blank">Full Text</a>]
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<a id="Yang1995" class="mim-anchor"></a>
<div class="">
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Yang, R.-B., Foster, D. C., Garbers, D. L., Fulle, H.-J.
<strong>Two membrane forms of guanylyl cyclase found in the eye.</strong>
Proc. Nat. Acad. Sci. 92: 602-606, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7831337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7831337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7831337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.92.2.602" target="_blank">Full Text</a>]
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<a id="Yang1996" class="mim-anchor"></a>
<div class="">
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Yang, R.-B., Fulle, H.-J., Garbers, D. L.
<strong>Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina.</strong>
Genomics 31: 367-372, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838319</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/geno.1996.0060" target="_blank">Full Text</a>]
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<a id="Yzer2006" class="mim-anchor"></a>
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Yzer, S., Leroy, B. P., De Baere, E., de Ravel, T. J., Zonneveld, M. N., Voesenek, K., Kellner, U., Martinez Ciriano, J. P., de Faber, J.-T. H. N., Rohrschneider, K., Roepman, R., den Hollander, A. I., Cruysberg, J. R., Meire, F., Casteels, I., van Moll-Ramirez, N. G., Allikmets, R., van den Born, L. I., Cremers, F. P. M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1167/iovs.05-0848" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 04/04/2018<br>Marla J. F. O'Neill - updated : 12/15/2017<br>Jane Kelly - updated : 05/21/2015<br>Patricia A. Hartz - updated : 6/4/2013<br>Marla J. F. O'Neill - updated : 11/9/2010<br>Marla J. F. O'Neill - updated : 12/14/2009<br>Victor A. McKusick - updated : 11/1/2002<br>Michael J. Wright - updated : 7/31/2002<br>Jane Kelly - updated : 12/13/2001<br>George E. Tiller - updated : 3/5/2001<br>Victor A. McKusick - updated : 11/2/2000<br>Jane Kelly - updated : 6/28/2000<br>Victor A. McKusick - updated : 4/12/1999<br>Victor A. McKusick - updated : 9/14/1998<br>Victor A. McKusick - updated : 7/9/1998
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Victor A. McKusick : 11/8/1994
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carol : 09/07/2022<br>carol : 09/03/2019<br>alopez : 08/28/2019<br>carol : 04/04/2018<br>carol : 12/18/2017<br>carol : 12/15/2017<br>carol : 05/21/2015<br>mgross : 6/4/2013<br>wwang : 6/10/2011<br>wwang : 11/16/2010<br>terry : 11/9/2010<br>carol : 4/5/2010<br>wwang : 12/14/2009<br>carol : 5/27/2009<br>terry : 5/27/2009<br>terry : 5/27/2009<br>carol : 5/26/2009<br>alopez : 6/11/2004<br>tkritzer : 11/7/2002<br>tkritzer : 11/4/2002<br>terry : 11/1/2002<br>cwells : 8/1/2002<br>terry : 7/31/2002<br>alopez : 12/14/2001<br>alopez : 12/13/2001<br>alopez : 3/12/2001<br>alopez : 3/8/2001<br>cwells : 3/6/2001<br>alopez : 3/6/2001<br>cwells : 3/5/2001<br>cwells : 3/5/2001<br>mcapotos : 11/16/2000<br>mcapotos : 11/13/2000<br>terry : 11/2/2000<br>alopez : 6/28/2000<br>carol : 4/12/1999<br>carol : 4/2/1999<br>carol : 4/2/1999<br>alopez : 2/25/1999<br>carol : 9/16/1998<br>terry : 9/14/1998<br>carol : 8/13/1998<br>carol : 7/15/1998<br>terry : 7/9/1998<br>jenny : 12/6/1996<br>mark : 12/1/1996<br>terry : 11/21/1996<br>terry : 6/26/1996<br>terry : 6/21/1996<br>mark : 3/20/1996<br>terry : 3/11/1996<br>carol : 11/9/1994<br>terry : 11/8/1994
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<strong>*</strong> 600179
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GUANYLATE CYCLASE 2D, RETINAL; GUCY2D
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</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
GUC2D<br />
GUANYLATE CYCLASE 2D, MEMBRANE<br />
GUCY2E, MOUSE, HOMOLOG OF<br />
ROD OUTER SEGMENT MEMBRANE GUANYLATE CYCLASE; ROSGC<br />
RETGC<br />
RETGC1
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong><em>HGNC Approved Gene Symbol: GUCY2D</em></strong>
</span>
</p>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: 17p13.1
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : 17:8,002,615-8,020,342 </span>
</em>
</strong>
<span class="small">(from NCBI)</span>
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene-Phenotype Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="4">
<span class="mim-font">
17p13.1
</span>
</td>
<td>
<span class="mim-font">
?Choroidal dystrophy, central areolar 1
</span>
</td>
<td>
<span class="mim-font">
215500
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
Cone-rod dystrophy 6
</span>
</td>
<td>
<span class="mim-font">
601777
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant; Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
Leber congenital amaurosis 1
</span>
</td>
<td>
<span class="mim-font">
204000
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
Night blindness, congenital stationary, type 1I
</span>
</td>
<td>
<span class="mim-font">
618555
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<div>
<h4>
<span class="mim-font">
<strong>Cloning and Expression</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Three-prime, 5-prime-cyclic guanosine monophosphate (cGMP) is the intracellular second messenger regulating phototransduction in mammals. The level of cGMP in photoreceptor cells is controlled by the cGMP-hydrolyzing enzyme cGMP phosphodiesterase and the cGMP-producing enzyme guanylate cyclase. Two major forms of cyclases are recognized, the particulate (membrane) and the soluble forms. The membrane guanylate cyclases are composed of large single subunits consisting of a ligand-binding N-terminal segment, a transmembrane domain, an internal protein kinase homology region, and a C-terminal catalytic domain. The highly homologous membrane guanylate cyclases include NPR1 (natriuretic peptide receptor A; 108960), NPR2 (natriuretic peptide receptor B; 108961), and NPR3 (natriuretic peptide receptor C; 108962). Shyjan et al. (1992) cloned a human photoreceptor guanylate cyclase, called retGC (GUCY2D). The predicted protein sequence is closely related to the other membrane guanylate cyclases, and all structural domains are well conserved. However, expressed photoreceptor guanylate cyclase is not activated by natriuretic peptides. </p><p>Yang et al. (1995) cloned 2 guanylyl cyclases, Gucy2e and Gucyf (300041), from a rat eye cDNA library. These 2 rat genes are expressed in retina. The mouse and rat Gucy2e genes are homologs of human GUCY2D (Scott, 2009). </p><p>The human GUCY2D protein is 87% identical to its mouse counterpart (Perrault et al., 1996). </p><p>Duda et al. (1999) stated that GUCY2D, which they called rod outer segment membrane guanylate cyclase (ROS-GC1), was the original member of the subfamily of membrane guanylate cyclases with 2 Ca(2+) switches referred to as calcium-regulated modules (CRMs) and designated CRM1 and CRM2. These are separately located within the intracellular domain of the cyclase. CRM1 switches on the enzyme at nanomolar concentrations of calcium ion and is linked with phototransduction; CRM2 stimulates at micromolar calcium ion concentrations and is predicted to be linked with retinal synaptic activity. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene Structure</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Perrault et al. (1996) determined that the human GUCY2D gene spans 16 kb and contains 20 exons. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Oliveira et al. (1994) used PCR analysis of human-rodent somatic cell hybrids to map the GUCY2D locus to chromosome 17. The assignment was confirmed and regionalized to chromosome 17p13.1 by fluorescence in situ hybridization. </p><p>By interspecific backcross analysis, Yang et al. (1996) mapped the mouse Gucy2e gene to chromosome 11 in a region of syntenic homology to human 17p13 known to contain loci for autosomal dominant retinitis pigmentosa (600059) and Leber congenital amaurosis (204000). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene Function</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By coimmunoprecipitation of mouse retinal extracts, Azadi et al. (2010) found that Rd3 (180040) bound the guanylate cyclases Gc1 and Gc2, encoded by GUCY2D and GUCY2F (300041), respectively. They confirmed interaction of Rd3 with Gc1 in transfected HEK293 cells. A short C-terminal segment of Gc1 was required for Rd3 binding. When expressed alone in COS-7 cells, Rd3 colocalized with the endosomal recycling marker Rab11 (see RAB11A; 605570) in a pattern characteristic of intracellular vesicles, whereas Gc1 localized in a perinuclear distribution characteristic of endoplasmic reticulum (ER). When coexpressed, Gc1 was exported from the ER to endosomal vesicles containing Rd3 and Rab11. Retinal extracts from Rd3 mutant mice lacked Gc1 protein expression and showed reduced Gc2 protein expression compared with wildtype. The GC-activating proteins Gcap1 (GUCA1A; 600364) and Gcap2 (GUCA1B; 602275) also showed reduced expression in Rd3 mice, as well as mislocalization to the inner segment of photoreceptor cells. Azadi et al. (2010) proposed that RD3 may be an accessory protein required for vesicle trafficking of GCs from inner to outer segments of rod and cone cells and that it may modulate GC enzymatic activity. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
By homozygosity mapping in consanguineous families of North African origin, Camuzat et al. (1995) mapped a gene for Leber congenital amaurosis (LCA1; 204000) to 17p13.1. Camuzat et al. (1996) provided evidence of genetic heterogeneity, finding that LCA1 accounted for 8/15 LCA families in their series. Based on 3 key recombinants, Perrault et al. (1996) were able to reduce the interval encompassing the LCA1 gene to a critical region of less than 1 cM. Starting from flanking markers, they ordered 12 YAC clones on 17p13.1. Of the candidate genes expressed in the retina and located on chromosome 17, none mapped to these YACs except the gene for retinal guanylate cyclase. Perrault et al. (1996) found 2 missense mutations (600179.0001; 600179.0004) and 2 frameshift mutations (600179.0002; 600179.0003) associated with LCA1. As specific guanylate cyclase activating proteins (GCAPs) are required for retinal guanylate cyclase activity, the study of Perrault et al. (1996) raised the question of whether some LCA cases unlinked to 17p13 could be accounted for by mutations in GCAP genes, which include the GUCA1 gene (600364) on 6p21.1. </p><p>Perrault et al. (2000) screened the whole coding sequence of the RETGC1 gene in 118 patients affected with Leber congenital amaurosis. They found 22 different mutations in 24 unrelated families originating from various countries. All RETGC1 mutations consistently caused congenital cone-rod dystrophy. RETGC1 is an essential protein implicated in the phototransduction cascade, especially in the recovery of the dark state after the excitation process of photoreceptor cells by light stimulation. Perrault et al. (2000) postulated that the RETGC1 mutations hinder the restoration of the basal level of cGMP of cone and rod photoreceptor cells, leading to a situation equivalent to consistent light exposure during photoreceptor development, explaining the severity of the visual disorder at birth. </p><p>Khan et al. (2014) performed targeted next-generation sequencing with a panel of 14 LCA genes in 23 'strictly defined' LCA patients from 19 endogamous and/or consanguineous Saudi Arabian families and identified mutations in the GUCY2D gene in 5 probands, 3 of whom had concomitant neurodevelopmental delay. </p><p><strong><em>Cone-Rod Dystrophy 6</em></strong></p><p>
Leber congenital amaurosis is inherited as an autosomal recessive. Kelsell et al. (1998) demonstrated that mutations in the GUCY2D gene are responsible also for a dominant form of cone-rod dystrophy, which they referred to as CORD6 (601777). </p><p>Payne et al. (2001) studied 40 patients: 27 with autosomal dominant macular dystrophy and 13 with autosomal dominant cone or cone-rod dystrophy. Two patients were found to carry the R838C mutation (600179.0006) and 1 the R838H mutation (600179.0008). Combining these results with those of Kelsell et al. (1998), Payne et al. (2001) estimated the frequency of mutations at codon 838 of the GUCY2D gene among patients with autosomal dominant macular cone or cone-rod dystrophy to be 6.7%. However, if only the 3 mutations in the 13 patients with cone or cone-rod dystrophy are considered, the estimated frequency of mutations is 23%. </p><p>In affected members of a 3-generation family segregating autosomal dominant cone-rod dystrophy, Perrault et al. (1998) identified a complex mutation event involving 3 consecutive missense mutations within a single exon (600179.0007). </p><p>In affected members of a consanguineous Turkish family segregating autosomal recessive CORD mapping to chromosome 17p13.3, Ugur Iseri et al. (2010) identified homozygosity for a missense mutation (600179.0010) in the GUCY2D gene. </p><p><strong><em>Central Areolar Choroidal Dystrophy 1</em></strong></p><p>
In a large Irish pedigree with central areolar choroidal dystrophy mapping to chromosome 17p13 (CACD1; 215500), Hughes et al. (2012) identified heterozygosity for a missense mutation in the GUCY2D gene (V933A; 600179.0011) that segregated with disease. The authors stated that the CACD phenotype is distinctive, although it shares features in common with cone dystrophy and cone-rod dystrophy. </p><p><strong><em>Congenital Stationary Night Blindness, Type 1I</em></strong></p><p>
In 5 patients from 4 families with congenital stationary night blindness (CSNB1I; 618555), Stunkel et al. (2018) identified compound heterozygosity for mutations in the GUCY2D gene (see, e.g., 600179.0012-600179.0016). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Wilkie et al. (2000) studied the biochemical effects of various mutations at codon 838 in RETGC1: the 3 disease-causing substitutions (R838C, 600179.0006; R838H, 600179.0008 and R838S, 600179.0005) and 4 artificial mutations (R838A, R838E, R838L, and R838K). Assay of GCAP1-stimulated cyclase activity in vitro showed that, compared with wildtype, R838E, R838L and R838K had only low activity, whereas R838A, R838C, R838H, and R838S had activity equal to or greater than wildtype at low Ca(2+) concentrations as well as a higher apparent affinity for GCAP1 than did wildtype. The Ca(2+) sensitivity of the GCAP1 activation was also altered with marked residual activity at high Ca(2+), the effect increasing in this order: wildtype, R838C, R838H, R838A, R838S. Within the photoreceptor, this would result in a failure to inactivate cyclase activity at high physiologic Ca(2+) concentrations. Among the 3 disease-associated mutations, the effect correlated directly with disease severity. The wildtype and R838H mutant displayed a difference in pH sensitivity, with the mutant showing a higher specific activity with pH greater than 6.0. Site 838 is in the dimerization domain that forms a coiled-coil in the active protein. A computer-aided structure prediction of this region indicated that R838 in the wildtype breaks the structure at 4 helical turns, and there is an increasing tendency for the structure to continue for further turns in the order R838C; R838H,S,K; R838E; R838A; R838L. </p><p>Downes et al. (2001) described the phenotype and electrophysiologic responses in 4 British families, 3 with an R838C mutation and 1 with an R838H mutation in the GUCY2D gene. Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Electrophysiologic testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. The authors concluded that the phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D was distinctive, with predominantly cone system involvement. There was some variation in severity within the 3 families with the R838C mutation. Families with the R838C or R838H mutations had a much milder phenotype than the families previously described with the E837D/R838S mutation (600179.0005) in GUCY2D. </p><p>Sharon et al. (2018) reviewed reported GUCY2D mutations, noting that LCA1-associated mutations were distributed throughout the protein, whereas CORD6-associated mutations were limited to the dimer domain. The authors analyzed published functional studies of GUCY2D missense mutations and found 41 such variants, including 21 associated with LCA1 and 7 with CORD6. A clear genotype-phenotype correlation was demonstrated, in which LCA1-associated mutations showed either reduced ability or complete inability to synthesize cGMP from GTP, whereas CORD6-associated mutations were functional, but shifted the Ca(2+) sensitivity of the Gc1-GCAP complex. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>ALLELIC VARIANTS</strong>
</span>
<strong>16 Selected Examples):</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0001 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, PHE565SER
<br />
SNP: rs61749755,
gnomAD: rs61749755,
ClinVar: RCV000009944, RCV000084839, RCV005053885
</span>
</div>
<div>
<span class="mim-text-font">
<p>In all sibs with Leber congenital amaurosis (LCA1; 204000) in 2 consanguineous Arab-Algerian families, Perrault et al. (1996) found homozygosity for a T-to-C transition in exon 8 at nucleotide 1767 of the GUC2D gene. The nucleotide change converted phenylalanine to serine in the protein. The substitution of an aromatic nonpolar amino acid by an uncharged polar amino acid within the kinase-like domain markedly altered the hydrophobicity of the protein and was expected to affect its stability severely. Perrault et al. (1996) reported the predicted change at amino acid 589 (F589S), but Duda et al. (1999) stated that the correct position is 565. </p><p>Duda et al. (1999) showed that the bovine F514S mutation, which corresponds to the human F565S mutation, severely damages the intrinsic cyclase activity of ROS-GC1 and inactivates its CRM1 switch but does not affect the CRM2 switch. In addition, on the basis of the established modulatory features of ROS-GC1, Duda et al. (1999) predicted that in 2 other forms of Leber congenital amaurosis involving deletion of nucleotide 460C (600179.0002) or 693C (600179.0003), there is a frameshift in the GUCY2D gene that results in nonexpression of the cyclase. </p><p>Yzer et al. (2006) reported a 25-year-old woman with LCA (patient 22597) who had 2 affected sibs; she was homozygous for the F565S mutation (c.1694T-C) in GUCY2D. An unrelated 1-year-old girl with LCA (patient 441) was compound heterozygous for F565S and an R768W substitution in GUCY2D (600179.0012). </p><p>Sharon et al. (2018) noted that the F565S mutation arose from a c.1694T-C transition (c.1694T-C, NM_000180.3) in exon 8 of GUCY2D. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0002 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, 1-BP DEL, 460C
<br />
SNP: rs61749670,
gnomAD: rs61749670,
ClinVar: RCV000009945, RCV000084897, RCV000693446, RCV001003037, RCV002498447, RCV005053901
</span>
</div>
<div>
<span class="mim-text-font">
<p>In a Jewish Sephardi family of Tunisian origin, Perrault et al. (1996) found that members with Leber congenital amaurosis (204000) were homozygous for a 1-bp deletion (460delC) in exon 2 at nucleotide 460 of GUC2D that modified the downstream amino acid sequence, abolished a SmaI restriction site, and resulted in a premature translation termination at codon 165. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0003 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, 1-BP DEL, 693C
<br />
SNP: rs61749671,
ClinVar: RCV000009946, RCV000084903
</span>
</div>
<div>
<span class="mim-text-font">
<p>In members of an Arab family of Tunisian origin affected with Leber congenital amaurosis (204000), Perrault et al. (1996) observed a homozygous 1-bp deletion in exon 2 at nucleotide 693 (693delC) of GUC2D that modified the downstream amino acid sequence, created a BspMI restriction site, and resulted in a premature translation termination at codon 215. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0004 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ALA52SER
<br />
SNP: rs61749665,
gnomAD: rs61749665,
ClinVar: RCV000009947, RCV000078318, RCV000084835, RCV001518075, RCV002225071, RCV002490349, RCV005053886
</span>
</div>
<div>
<span class="mim-text-font">
<p>In all sibs with Leber congenital amaurosis (204000) in a consanguineous Arab Tunisian family, Perrault et al. (1996) found homozygosity for a G-to-T transversion at nucleotide 227 of GUC2D converting an alanine into a serine (A52S). Heterozygosity for the same mutation was detected in affected members of a family of Basque ancestry. As the same base change was detected in 2 of 100 controls, it was difficult to decide whether this was a disease-causing mutation or a rare polymorphism. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0005 &nbsp; CONE-ROD DYSTROPHY 6</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, GLU837ASP AND ARG838SER
<br />
SNP: rs28933695, rs61750172,
gnomAD: rs61750172,
ClinVar: RCV000009948, RCV000009950, RCV000084860, RCV000084861, RCV001854486
</span>
</div>
<div>
<span class="mim-text-font">
<p>In a 4-generation British family with cone-rod dystrophy (CORD6; 601777), Kelsell et al. (1997) showed linkage between the disorder and 17p13-p12. Cone-rod dystrophy in this family displayed an early onset, with loss of central vision reported before 7 years of age and peripheral field loss by the fourth decade. A notable feature was marked photophobia, particularly when dark-adapted. Funduscopy showed a 'bull's eye' maculopathy early in the disease, with later involvement of the peripheral retina. Electroretinography showed no detectable cone responses early in the disease, with progressive abnormality of rod responses appearing later. Kelsell et al. (1998) studied the GUC2D gene because it maps to the same chromosomal area. Direct sequence analysis of all 18 coding exons of the gene demonstrated a heterozygous alteration in exon 13: 2584G-C, predicted to cause a glu837-to-asp (E837D) amino acid substitution. </p><p>Gregory-Evans et al. (2000) stated that further analysis of the family originally studied by Kelsell et al. (1997) led to a reappraisal of the mutation, redefined as glu837 to asp/arg838 to ser. They described the clinical features in this family (see 601777). </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0006 &nbsp; CONE-ROD DYSTROPHY 6</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ARG838CYS
<br />
SNP: rs61750172,
gnomAD: rs61750172,
ClinVar: RCV000009949, RCV000009950, RCV000084862, RCV001003042, RCV001065465, RCV001074299, RCV001197374, RCV001376215
</span>
</div>
<div>
<span class="mim-text-font">
<p>Kelsell et al. (1998) found another heterozygous mutation of the GUC2D gene in a family with cone-rod dystrophy (CORD6; 601777) with features somewhat different from that of the original CORD6 family described in 600179.0005. In 3 families carrying this second mutation (arg838 to cys; R838C), affected individuals, although aware of poor vision in bright light from an early age, suffered loss of central vision in the late second or third decade, later than was found in the original family with the E837D mutation. The fundus appearance of affected members of these 3 families was, however, very similar to that of the original family. Electrophysiologic testing revealed marked loss of photopic function by the mid-teens, with scotopic function becoming compromised later. Genealogic studies failed to show a relationship between the 3 families. The R838C amino acid substitution resulted from a C-to-T transition at nucleotide 2585. Alignment of the portion of membrane-bound guanylate cyclases in this domain, represented by codons 809 to 871, showed that both glu837 and arg838 are fully conserved. </p><p>In 38 affected members of a large multigenerational family from eastern Tennessee with autosomal dominant progressive cone dystrophy, originally described by Small and Gehrs (1996), Udar et al. (2003) identified the R838C mutation in the GUCY2D gene. The mutation was also detected in 2 unaffected family members, but was not found in 22 additional unaffected family members or 200 control chromosomes. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0007 &nbsp; CONE-ROD DYSTROPHY 6</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, GLU837ASP, ARG838CYS, AND THR839MET
<br />
SNP: rs61750172, rs61750174,
gnomAD: rs61750172, rs61750174,
ClinVar: RCV000009948, RCV000009949, RCV000009950, RCV000084860, RCV000084862, RCV000084864, RCV001003042, RCV001065465, RCV001074299, RCV001197374, RCV001239266, RCV001376215
</span>
</div>
<div>
<span class="mim-text-font">
<p>In 6 affected members from a 3-generation family with autosomal dominant cone-rod dystrophy (CORD6; 601777), Perrault et al. (1998) identified heterozygosity for a complex mutational event involving 3 consecutive missense mutations in exon 13: (1) a G-to-C transversion at nucleotide 2584, changing a glutamate to an aspartate at codon 837 (E837D); (2) a C-to-T transition at nucleotide 2585, changing an arginine to a cysteine at codon 838 (R838C); and (3) a C-to-T transition at nucleotide 2589, changing a threonine to a methionine at codon 839 (T839M). This triple mutation was considered to represent a gene conversion event. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0008 &nbsp; CONE-ROD DYSTROPHY 6</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ARG838HIS
<br />
SNP: rs61750173,
ClinVar: RCV000009951, RCV000084863, RCV000504851, RCV000787614, RCV001003043, RCV001228516, RCV001271114, RCV001723556, RCV003324497
</span>
</div>
<div>
<span class="mim-text-font">
<p>In a patient with cone-rod dystrophy-6 (CORD6; 601777), Weigell-Weber et al. (2000) detected a G-to-A transition of the GCGC stretch at position 2586 in exon 13 of the GUCY2D gene, resulting in a conservative arg838-to-his (R838H) substitution. </p><p>In 8 affected members of a Caucasian American family with cone dystrophy, Udar et al. (2003) identified the R838H mutation in the GUCY2D gene. The mutation was not found in 5 unaffected family members or 200 control chromosomes. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0009 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, 1-BP DEL, 2943G
<br />
SNP: rs61750185,
gnomAD: rs61750185,
ClinVar: RCV000084877, RCV001250850, RCV001381496, RCV004748576, RCV004815026, RCV004815027, RCV005053898
</span>
</div>
<div>
<span class="mim-text-font">
<p>Hanein et al. (2002) identified a homozygous 2943G deletion (2943delG) in the GUCY2D gene in 3 unrelated and nonconsanguineous Leber congenital amaurosis (204000) families of Finnish origin, suggesting a founder effect. No linkage disequilibrium was found using polymorphic markers flanking the GUCY2D gene, supporting the view that the mutation is very ancient. Haplotype studies and Bayesian calculation pointed the founder mutation to 150 generations (i.e., 3,000 years ago). </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0010 &nbsp; CONE-ROD DYSTROPHY 6</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ILE949THR
<br />
SNP: rs267606857,
ClinVar: RCV000009953
</span>
</div>
<div>
<span class="mim-text-font">
<p>In 6 affected members of a consanguineous Turkish family segregating autosomal recessive cone-rod dystrophy-6 (CORD6; 601777), Ugur Iseri et al. (2010) identified homozygosity for a 2846T-C transition in exon 15 of the GUCY2D gene, resulting in an ile949-to-thr (I949T) substitution at a highly conserved residue in the catalytic domain. The mutation was not detected in 186 control chromosomes. Ugur Iseri et al. (2010) predicted that substitution of hydrophobic isoleucine with polar threonine in this region would interfere with proper folding of the helical segment and affect function of the catalytic domain, and they proposed that the I949T mutation does not abolish but only decreases enzymatic activity. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0011 &nbsp; CENTRAL AREOLAR CHOROIDAL DYSTROPHY 1 (1 family)</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, VAL933ALA
<br />
SNP: rs1567961904,
ClinVar: RCV000755725
</span>
</div>
<div>
<span class="mim-text-font">
<p>In a large Irish pedigree with central areolar choroidal dystrophy-1 (CACD1; 215500), originally reported by Lotery et al. (1996), Hughes et al. (2012) identified heterozygosity for a point mutation (chr17.7,918,674T-C, GRCh37) in exon 15 of the GUCY2D gene, resulting in a val933-to-ala (V933A) substitution within the catalytic domain. The mutation segregated with disease and was not found in 7 control samples or in the 1000 Genomes Project database. No functional studies were performed. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0012 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I, INCLUDED
</span>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ARG768TRP
<br />
SNP: rs61750168,
gnomAD: rs61750168,
ClinVar: RCV000084856, RCV000543628, RCV000787613, RCV000850093, RCV000850094, RCV001075745, RCV002477250, RCV004748575, RCV005053896
</span>
</div>
<div>
<span class="mim-text-font">
<p />
<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
In 3 patients (designated 20955, 21557, and 22018) with Leber congenital amaurosis (LCA1; 204000) Yzer et al. (2006) identified homozygosity for a c.2302C-T transition in exon 12 of the GUCY2D gene, resulting in an arg768-to-trp (R768W) substitution. Two more LCA patients were compound heterozygous for R768W and another missense mutation in GUCY2D, including the F565S mutation (600179.0001) in 1 of them (patient 441). The 3 homozygous patients were severely affected, with no light perception upon initial examination in infancy and no signs of improvement later in life. The authors noted that the 8 R768W alleles were Dutch or Belgian in origin, suggestive of a founder effect in the northwestern region of Europe. </p><p>Jacobson et al. (2013) reported 10 patients with LCA who carried the R768W mutation in the GUCY2D gene, 2 in homozygosity and 8 in compound heterozygosity. One of the compound heterozygotes (patient 2) also carried the Q545X mutation (600179.0015). The patients were all of British/Irish or Scandinavian ancestry, except for 1 Greek homozygote. </p><p><strong><em>Night Blindness, Congenital Stationary, Type1I</em></strong></p><p>
In a brother and sister (patients 1 and 4), ages 17 years and 13 years, respectively, with type 1I congenital stationary night blindness (CSNB1I; 618555), Stunkel et al. (2018) identified compound heterozygosity for missense mutations in the GUCY2D gene: an arg768-to-trp (R768W) substitution, and a leu911-to-phe (L911F; 600179.0013) substitution. The boy had night blindness from infancy, whereas his sister became symptomatic at age 12 years; both had normal visual acuity. Also, in an unrelated 53-year-old woman (patient 5) with CSNB, the authors identified compound heterozygosity for the R768W mutation and an arg761-to-trp (R761W; 600179.0014) substitution in GUCY2D. In addition to night blindness, the older woman exhibited constricted visual fields and bone spicule-like pigmentation in the retinal periphery, but visual acuity remained intact. Stunkel et al. (2018) reported that the R761W variant was present in the ExAC database, in heterozygous state. </p><p>Sharon et al. (2018) noted that the R768W mutation arose from a c.2302C-T transition (c.2302C-T, NM_000180.3) in exon 12 of GUCY2D. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0013 &nbsp; NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, LEU911PHE
<br />
ClinVar: RCV000850095
</span>
</div>
<div>
<span class="mim-text-font">
<p>For discussion of the leu911-to-phe (L911F) substitution that was found in compound heterozygous state in sibs (patients 1 and 4) with congenital stationary night blindness (CSNB1I; 618555) by Stunkel et al. (2018), see 600179.0012. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0014 &nbsp; NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ARG761TRP
<br />
SNP: rs200637525,
gnomAD: rs200637525,
ClinVar: RCV001059685, RCV002290577, RCV004813659
</span>
</div>
<div>
<span class="mim-text-font">
<p>For discussion of the arg761-to-trp (R761W) substitution that was found in compound heterozygous state in a 52-year-old woman (patient 5) with congenital stationary night blindness (CSNB1I; 618555) by Stunkel et al. (2018), see 600179.0012. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0015 &nbsp; LEBER CONGENITAL AMAUROSIS 1</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I, INCLUDED
</span>
</div>
<div>
<span class="mim-text-font">
GUCY2D, GLN545TER
<br />
SNP: rs1290420698,
ClinVar: RCV000850097, RCV000850098, RCV003768615, RCV004726700, RCV005053957
</span>
</div>
<div>
<span class="mim-text-font">
<p />
<p><strong><em>Leber Congenital Amaurosis 1</em></strong></p><p>
Jacobson et al. (2013) studied a 7-year-old boy (patient 2) with Leber congenital amaurosis-1 (LCA1; 204000), who was compound heterozygous for the R768W mutation in the GUCY2D gene (600179.0012) and a gln545-to-ter (Q545X) substitution. The authors noted that the Q545X mutation truncates a major portion of the intracellular segment of the cyclase, thus eliminating its entire function. Electroretinography (ERG) in the proband showed no detectable cone function but considerable retention of rod function. In addition to LCA, the boy had been diagnosed with mild autism. </p><p><strong><em>Night Blindness, Congenital Stationary, Type1I</em></strong></p><p>
In a 15-year-old boy (patient 2) with type 1I congenital stationary night blindness (CSNB1I; 618555), Stunkel et al. (2018) identified compound heterozygosity for a nonsense mutation (gln545-to-ter; Q545X) and a missense mutation (arg83-to-cys; R83C; 600179.0016). Sharon et al. (2018) noted that the Q545X mutation arose from a c.1633C-T transition (c.1633C-T, NM_000180.3) in exon 7 of GUCY2D. The proband, who had lifelong night blindness, showed no rod response on ERG, but had nearly normal 30-Hz flicker cone responses with 20/20 visual acuity. ERG amplitudes decreased over 5 years of follow-up and he developed peripheral visual field defects, but visual acuity remained stable. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0016 &nbsp; NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1I</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
GUCY2D, ARG83CYS
<br />
ClinVar: RCV000850099
</span>
</div>
<div>
<span class="mim-text-font">
<p>For discussion of the arg83-to-cys (R83C) substitution that was found in compound heterozygous state in a 15-year-old boy (patient 2) with congenital stationary night blindness (CSNB1I; 618555) by Stunkel et al. (2018), see 600179.0015. </p>
</span>
</div>
<div>
<br />
</div>
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
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<p class="mim-text-font">
Azadi, S., Molday, L. L., Molday, R. S.
<strong>RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells.</strong>
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[Full Text: https://doi.org/10.1073/pnas.1010460107]
</p>
</li>
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<p class="mim-text-font">
Camuzat, A., Dollfus, H., Rozet, J.-M., Gerber, S., Bonneau, D., Bonnemaison, M., Briard, M.-L., Dufier, J.-L., Ghazi, I., Leowski, C., Weissenbach, J., Frezal, J., Munnich, A., Kaplan, J.
<strong>A gene for Leber&#x27;s congenital amaurosis maps to chromosome 17p.</strong>
Hum. Molec. Genet. 4: 1447-1452, 1995.
[PubMed: 7581387]
[Full Text: https://doi.org/10.1093/hmg/4.8.1447]
</p>
</li>
<li>
<p class="mim-text-font">
Camuzat, A., Rozet, J.-M., Dollfus, H., Gerber, S., Perrault, I., Weissenbach, J., Munnich, A., Kaplan, J.
<strong>Evidence of genetic heterogeneity of Leber&#x27;s congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13.</strong>
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</p>
</li>
<li>
<p class="mim-text-font">
Downes, S. M., Payne, A. M., Kelsell, R. E., Fitzke, F. W., Holder, G. E., Hunt, D. M., Moore, A. T., Bird, A. C.
<strong>Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.</strong>
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</p>
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<p class="mim-text-font">
Duda, T., Venkataraman, V., Goraczniak, R., Lange, C., Koch, K-W., Sharma, R. K.
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</p>
</li>
<li>
<p class="mim-text-font">
Gregory-Evans, K., Kelsell, R. E., Gregory-Evans, C. Y., Downes, S. M., Fitzke, F. W., Holder, G. E., Simunovic, M., Mollon, J. D., Taylor, R., Huntt, D. M., Bird, A. C., Moore, A. T.
<strong>Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.</strong>
Ophthalmology 107: 55-61, 2000.
[PubMed: 10647719]
[Full Text: https://doi.org/10.1016/s0161-6420(99)00038-x]
</p>
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<li>
<p class="mim-text-font">
Hanein, S., Perrault, I., Olsen, P., Lopponen, T., Hietala, M., Gerber, S., Jeanpierre, M., Barbet, F., Ducroq, D., Hakiki, S., Munnich, A., Rozet, J.-M., Kaplan, J.
<strong>Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin.</strong>
Hum. Mutat. 20: 322-323, 2002.
[PubMed: 12325031]
[Full Text: https://doi.org/10.1002/humu.9067]
</p>
</li>
<li>
<p class="mim-text-font">
Hughes, A. E., Meng, W., Lotery, A. J., Bradley, D. T.
<strong>A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy.</strong>
Invest. Ophthal. Vis. Sci. 53: 4748-4753, 2012.
[PubMed: 22695961]
[Full Text: https://doi.org/10.1167/iovs.12-10061]
</p>
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<li>
<p class="mim-text-font">
Jacobson, S. G., Cideciyan, A. V., Peshenko, I. V., Sumaroka, A., Olshevskaya, E. V., Cao, L., Schwartz, S. B., Roman, A. J., Olivares, M. B., Sadigh, S., Yau, K.-W., Heon, E., Stone, E. M., Dizhoor, A. M.
<strong>Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants.</strong>
Hum. Molec. Genet. 22: 168-183, 2013.
[PubMed: 23035049]
[Full Text: https://doi.org/10.1093/hmg/dds421]
</p>
</li>
<li>
<p class="mim-text-font">
Kelsell, R. E., Evans, K., Gregory, C. Y., Moore, A. T., Bird, A. C., Hunt, D. M.
<strong>Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p.</strong>
Hum. Molec. Genet. 6: 597-600, 1997.
[PubMed: 9097965]
[Full Text: https://doi.org/10.1093/hmg/6.4.597]
</p>
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<li>
<p class="mim-text-font">
Kelsell, R. E., Gregory-Evans, K., Payne, A. M., Perrault, I., Kaplan, J., Yang, R.-B., Garbers, D. L., Bird, A. C., Moore, A. T., Hunt, D. M.
<strong>Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.</strong>
Hum. Molec. Genet. 7: 1179-1184, 1998.
[PubMed: 9618177]
[Full Text: https://doi.org/10.1093/hmg/7.7.1179]
</p>
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<p class="mim-text-font">
Khan, A. O., Al-Mesfer, S., Al-Turkmani, S., Bergmann, C., Bolz, H. J.
<strong>Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay.</strong>
Brit. J. Ophthal. 98: 1724-1728, 2014.
[PubMed: 24997176]
[Full Text: https://doi.org/10.1136/bjophthalmol-2014-305122]
</p>
</li>
<li>
<p class="mim-text-font">
Lotery, A. J., Ennis, K. T., Silvestri, G., Nicholl, S., McGibbon, D., Collins, A. D., Hughes, A. E.
<strong>Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.</strong>
Hum. Molec. Genet. 5: 705-708, 1996.
[PubMed: 8733141]
[Full Text: https://doi.org/10.1093/hmg/5.5.705]
</p>
</li>
<li>
<p class="mim-text-font">
Oliveira, L., Miniou, P., Viegas-Pequignot, E., Rozet, J.-M., Dollfus, H., Pittler, S. J.
<strong>Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1.</strong>
Genomics 22: 478-481, 1994.
[PubMed: 7806240]
[Full Text: https://doi.org/10.1006/geno.1994.1415]
</p>
</li>
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<p class="mim-text-font">
Payne, A. M., Morris, A. G., Downes, S. M., Johnson, S., Bird, A. C., Moore, A. T., Bhattacharya, S. S., Hunt, D. M.
<strong>Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. (Letter)</strong>
J. Med. Genet. 38: 611-647, 2001.
[PubMed: 11565546]
[Full Text: https://doi.org/10.1136/jmg.38.9.611]
</p>
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<p class="mim-text-font">
Perrault, I., Rozet, J. M., Calvas, P., Gerber, S., Camuzat, A., Dollfus, H., Chatelin, S., Souied, E., Ghazi, I., Leowski, C., Bonnemaison, M., Le Paslier, D., Frezal, J., Dufier, J.-L., Pittler, S., Munnich, A., Kaplan, J.
<strong>Retinal-specific guanylate cyclase gene mutations in Leber&#x27;s congenital amaurosis.</strong>
Nature Genet. 14: 461-464, 1996.
[PubMed: 8944027]
[Full Text: https://doi.org/10.1038/ng1296-461]
</p>
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<li>
<p class="mim-text-font">
Perrault, I., Rozet, J.-M., Gerber, S., Ghazi, I., Ducroq, D., Souied, E., Leowski, C., Bonnemaison, M., Dufier, J.-L., Munnich, A., Kaplan, J.
<strong>Spectrum of retGC1 mutations in Leber&#x27;s congenital amaurosis.</strong>
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[PubMed: 10951519]
[Full Text: https://doi.org/10.1038/sj.ejhg.5200503]
</p>
</li>
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<p class="mim-text-font">
Perrault, I., Rozet, J.-M., Gerber, S., Kelsell, R. E., Souied, E., Cabot, A., Hunt, D. M., Munnich, A., Kaplan, J.
<strong>A retGC-1 mutation in autosomal dominant cone-rod dystrophy. (Letter)</strong>
Am. J. Hum. Genet. 63: 651-654, 1998.
[PubMed: 9683616]
[Full Text: https://doi.org/10.1086/301985]
</p>
</li>
<li>
<p class="mim-text-font">
Scott, A. F.
<strong>Personal Communication.</strong>
Baltimore, Md. 5/2009.
</p>
</li>
<li>
<p class="mim-text-font">
Sharon, D., Wimberg, H., Kinarty, Y., Koch, K.-W.
<strong>Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D.</strong>
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[Full Text: https://doi.org/10.1016/j.preteyeres.2017.10.003]
</p>
</li>
<li>
<p class="mim-text-font">
Shyjan, A. W., de Sauvage, F. J., Gillett, N. A., Goeddel, D. V., Lowe, D. G.
<strong>Molecular cloning of a retina-specific membrane guanylyl cyclase.</strong>
Neuron 9: 727-737, 1992.
[PubMed: 1356371]
[Full Text: https://doi.org/10.1016/0896-6273(92)90035-c]
</p>
</li>
<li>
<p class="mim-text-font">
Small, K. W., Gehrs, K.
<strong>Clinical study of a large family with autosomal dominant progressive cone degeneration.</strong>
Am. J. Ophthal. 121: 1-12, 1996.
[PubMed: 8554074]
[Full Text: https://doi.org/10.1016/s0002-9394(14)70528-8]
</p>
</li>
<li>
<p class="mim-text-font">
Stunkel, M. L., Brodie, S. E., Cideciyan, A. V., Pfeifer, W. L., Kennedy, E. L., Stone, E. M., Jacobson, S. G., Drack, A. V.
<strong>Expanded retinal disease spectrum associated with autosomal recessive mutations in GUCY2D.</strong>
Am. J. Ophthal. 190: 58-68, 2018.
[PubMed: 29559409]
[Full Text: https://doi.org/10.1016/j.ajo.2018.03.021]
</p>
</li>
<li>
<p class="mim-text-font">
Udar, N., Yelchits, S., Chalukya, M., Yellore, V., Nusinowitz, S., Silva-Garcia, R., Vrabec, T., Maumenee, I. H., Donoso, L., Small, K. W.
<strong>Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.</strong>
Hum. Mutat. 21: 170-171, 2003.
[PubMed: 12552567]
[Full Text: https://doi.org/10.1002/humu.9109]
</p>
</li>
<li>
<p class="mim-text-font">
Ugur Iseri, S. A., Durlu, Y. K., Tolun, A.
<strong>A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber&#x27;s congenital amaurosis.</strong>
Europ. J. Hum. Genet. 18: 1121-1126, 2010.
[PubMed: 20517349]
[Full Text: https://doi.org/10.1038/ejhg.2010.81]
</p>
</li>
<li>
<p class="mim-text-font">
Weigell-Weber, M., Fokstuen, S., Torok, B., Niemeyer, G., Schinzel, A., Hergersberg, M.
<strong>Codons 837 and 838 in the retinal guanylate cyclase gene on chromosome 17p: hot spots for mutations in autosomal dominant cone-rod dystrophy?</strong>
Arch. Ophthal. 118: 300 only, 2000.
[PubMed: 10676808]
[Full Text: https://doi.org/10.1001/archopht.118.2.300]
</p>
</li>
<li>
<p class="mim-text-font">
Wilkie, S. E., Newbold, R. J., Deery, E., Walker, C. E., Stinton, I., Ramamurthy, V., Hurley, J. B., Bhattacharya, S. S., Warren, M. J., Hunt, D. M.
<strong>Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy.</strong>
Hum. Molec. Genet. 9: 3065-3073, 2000.
[PubMed: 11115851]
[Full Text: https://doi.org/10.1093/hmg/9.20.3065]
</p>
</li>
<li>
<p class="mim-text-font">
Yang, R.-B., Foster, D. C., Garbers, D. L., Fulle, H.-J.
<strong>Two membrane forms of guanylyl cyclase found in the eye.</strong>
Proc. Nat. Acad. Sci. 92: 602-606, 1995.
[PubMed: 7831337]
[Full Text: https://doi.org/10.1073/pnas.92.2.602]
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Yang, R.-B., Fulle, H.-J., Garbers, D. L.
<strong>Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina.</strong>
Genomics 31: 367-372, 1996.
[PubMed: 8838319]
[Full Text: https://doi.org/10.1006/geno.1996.0060]
</p>
</li>
<li>
<p class="mim-text-font">
Yzer, S., Leroy, B. P., De Baere, E., de Ravel, T. J., Zonneveld, M. N., Voesenek, K., Kellner, U., Martinez Ciriano, J. P., de Faber, J.-T. H. N., Rohrschneider, K., Roepman, R., den Hollander, A. I., Cruysberg, J. R., Meire, F., Casteels, I., van Moll-Ramirez, N. G., Allikmets, R., van den Born, L. I., Cremers, F. P. M.
<strong>Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis.</strong>
Invest. Ophthal. Vis. Sci. 47: 1167-1176, 2006.
[PubMed: 16505055]
[Full Text: https://doi.org/10.1167/iovs.05-0848]
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