4998 lines
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Entry
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- *138850 - GONADOTROPIN-RELEASING HORMONE RECEPTOR; GNRHR
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- OMIM
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<p>
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<span class="h4">*138850</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/138850">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000109163;t=ENST00000226413" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=2798" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=138850" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000109163;t=ENST00000226413" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000406,NM_001012763" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000406" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=138850" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00732&isoform_id=00732_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/GNRHR" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/183422,292053,299701,399777,722236,722238,957293,1628390,2290768,3334763,4504059,40807648,61676184,61891599,109731732,119625962,119625963" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P30968" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=2798" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000109163;t=ENST00000226413" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=GNRHR" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=GNRHR" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+2798" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/GNRHR" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:2798" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2798" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr4&hgg_gene=ENST00000226413.5&hgg_start=67737118&hgg_end=67754388&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=138850[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=138850[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000109163" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=GNRHR" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=GNRHR" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GNRHR" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GNRHR&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA28800" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:4421" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0025595.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:95790" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/GNRHR#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:95790" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2798/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=2798" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00018798;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2798" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=GNRHR&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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138850
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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GONADOTROPIN-RELEASING HORMONE RECEPTOR; GNRHR
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
GNRHR1<br />
|
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GRHR<br />
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LUTEINIZING HORMONE-RELEASING HORMONE RECEPTOR; LHRHR
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GNRHR" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNRHR</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/4/255?start=-3&limit=10&highlight=255">4q13.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr4:67737118-67754388&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'})">4:67,737,118-67,754,388</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/4/255?start=-3&limit=10&highlight=255">
|
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4q13.2
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Hypogonadotropic hypogonadism 7 without anosmia
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/146110"> 146110 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/138850" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/138850" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Gonadotropin-releasing hormone (GNRH; <a href="/entry/152760">152760</a>), a hypothalamic decapeptide, is a key neuroregulator of the reproductive process. It is synthesized by hypothalamic neurons, secreted in a pulsatile manner, and carried to the anterior lobe of the pituitary gland by way of the hypothalamohypophyseal portal circulation. The primary site of action of GNRH in the pituitary gland is the gonadotrope, the cell that expresses GNRH receptors and secretes gonadotropic hormones, which in turn regulate gametogenic and hormonal functions of the gonads. GNRH receptor is a member of the G protein-coupled, Ca(2+)-dependent family of receptors. Located on the cell surface of pituitary gonadotropes, GNRHR transduces signals from GNRH and modulates the synthesis and secretion of luteinizing hormone (<a href="/entry/152780">152780</a>) and follicle-stimulating hormone (<a href="/entry/136530">136530</a>).</p>
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<p><a href="#12" class="mim-tip-reference" title="Kakar, S. S., Musgrove, L. C., Devor, D. C., Sellers, J. C., Neill, J. D. <strong>Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor.</strong> Biochem. Biophys. Res. Commun. 189: 289-295, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1333190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1333190</a>] [<a href="https://doi.org/10.1016/0006-291x(92)91556-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1333190">Kakar et al. (1992)</a> isolated a cDNA for the GNRH receptor and showed that it encodes a protein with a transmembrane topology similar to that of other G protein-coupled 7-transmembrane-domain receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1333190" 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="Grosse, R., Schoneberg, T., Schultz, G., Gudermann, T. <strong>Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor.</strong> Molec. Endocr. 11: 1305-1318, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259321</a>] [<a href="https://doi.org/10.1210/mend.11.9.9966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259321">Grosse et al. (1997)</a> used RT-PCR of human pituitary poly(A)+ RNA to clone the full-length GNRHR gene and a second truncated cDNA characterized by a 128-bp deletion between nucleotide positions 522 and 651. The deletion causes a frameshift in the open reading frame, thus generating new coding sequence for a further 75 amino acids. The truncated cDNA arises from alternative splicing that uses a cryptic 3-prime splice site in exon 2. Translation products of approximately 45 to 50 and 42 kD were immunoprecipitated from COS-7 cells transfected with wildtype and truncated GNRHR cDNAs, respectively. The splice variant was incapable of ligand binding and signal transduction. Coexpression of wildtype and truncated proteins in transiently or stably transfected cells, resulted in impaired signaling via the wildtype GNRHR by reducing maximal agonist-induced inositol phosphate accumulation. This inhibitory effect depended on the amount of splice variant cDNA cotransfected and was specific for GNRHR. Coexpression of the wildtype and truncated GNRHRs resulted in impaired insertion of wildtype GNRHR into the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259321" 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>Using cDNA probes derived from a human pituitary cDNA library, <a href="#7" class="mim-tip-reference" title="Fan, N. C., Jeung, E.-B., Peng, C., Olofsson, J. I., Krisinger, J., Leung, P. C. K. <strong>The human gonadotropin-releasing hormone (GnRH) receptor gene: cloning, genomic organization and chromosomal assignment.</strong> Molec. Cell. Endocr. 103: R1-R6, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7958384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7958384</a>] [<a href="https://doi.org/10.1016/0303-7207(94)90087-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7958384">Fan et al. (1994)</a> screened a human genomic library and isolated 7 positive clones. The clones contained the entire protein coding region of the GNRHR gene, which is distributed among 3 exons and spans over 18.9 kb. The 2 introns, measuring 4.2 and 5.0 kb, were located within the open reading frame, indicating that the GNRHR gene is a member of the intron-containing class of the G protein-coupled receptor superfamily. Genomic Southern blot analysis demonstrated the presence of a single copy of the gene in the human genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7958384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Fan, N. C., Peng, C., Krisinger, J., Leung, P. C. K. <strong>The human gonadotropin-releasing hormone receptor gene: complete structure including multiple promoters, transcription initiation sites, and polyadenylation signals.</strong> Molec. Cell. Endocr. 107: R1-R8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7768323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7768323</a>] [<a href="https://doi.org/10.1016/0303-7207(94)03460-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7768323">Fan et al. (1995)</a> showed that the GNRHR mRNA is approximately 5 kb long, of which 987 bp comprise the coding region. The gene appears to have large 5-prime and 3-prime untranslated regions, including, respectively, multiple transcription initiation sites and polyadenylation signals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7768323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Kaiser, U. B., Dushkin, H., Altherr, M. R., Beier, D. R., Chin, W. W. <strong>Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5.</strong> Genomics 20: 506-508, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8034328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8034328</a>] [<a href="https://doi.org/10.1006/geno.1994.1211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8034328">Kaiser et al. (1994)</a> used mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4 to localize the GNRHR gene to 4q13.1-q21.1. Furthermore, using linkage analysis of single-strand conformation polymorphisms, they localized the murine homolog to mouse chromosome 5. Using PCR analysis of DNA from human/hamster somatic hybrid cell lines, <a href="#7" class="mim-tip-reference" title="Fan, N. C., Jeung, E.-B., Peng, C., Olofsson, J. I., Krisinger, J., Leung, P. C. K. <strong>The human gonadotropin-releasing hormone (GnRH) receptor gene: cloning, genomic organization and chromosomal assignment.</strong> Molec. Cell. Endocr. 103: R1-R6, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7958384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7958384</a>] [<a href="https://doi.org/10.1016/0303-7207(94)90087-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7958384">Fan et al. (1994)</a> assigned the GNRHR gene to chromosome 4. By in situ hybridization using a biotinylated cDNA probe, <a href="#26" class="mim-tip-reference" title="Morrison, N., Sellar, R. E., Boyd, E., Eidne, K. A., Connor, J. M. <strong>Assignment of the gene encoding the human gonadotropin-releasing hormone receptor to 4q13.2-13.3 by fluorescence in situ hybridization.</strong> Hum. Genet. 93: 714-715, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8005601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8005601</a>] [<a href="https://doi.org/10.1007/BF00201579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8005601">Morrison et al. (1994)</a> localized the GNRHR gene to 4q13.2-q13.3. By fluorescence in situ hybridization using a larger genomic clone as a probe, <a href="#20" class="mim-tip-reference" title="Leung, P. C. K., Squire, J., Peng, C., Fan, N., Hayden, M. R., Olofsson, J. I. <strong>Mapping of the gonadotropin-releasing hormone (GnRH) receptor gene to human chromosome 4q21.2 by fluorescence in situ hybridization.</strong> Mammalian Genome 6: 309-310, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7613048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7613048</a>] [<a href="https://doi.org/10.1007/BF00352431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7613048">Leung et al. (1995)</a> apparently achieved a more precise localization of the GNRHR gene to 4q21.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7958384+8034328+7613048+8005601" 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="Kottler, M. L., Lorenzo, F., Bergametti, F., Commercon, P., Souchier, C., Counis, R. <strong>Subregional mapping of the human gonadotropin-releasing hormone receptor (GnRH-R) gene to 4q between the markers D4S392 and D4S409.</strong> Hum. Genet. 96: 477-480, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557974</a>] [<a href="https://doi.org/10.1007/BF00191810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7557974">Kottler et al. (1995)</a> isolated YAC clones containing the GNRHR gene. Genetic analysis of the YACs showed that the gene lies between D4S409 and D4S392, which are located 76 and 77 cM, respectively, from the end of the short arm of chromosome 4. Furthermore, by fluorescence in situ hybridization, <a href="#15" class="mim-tip-reference" title="Kottler, M. L., Lorenzo, F., Bergametti, F., Commercon, P., Souchier, C., Counis, R. <strong>Subregional mapping of the human gonadotropin-releasing hormone receptor (GnRH-R) gene to 4q between the markers D4S392 and D4S409.</strong> Hum. Genet. 96: 477-480, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557974</a>] [<a href="https://doi.org/10.1007/BF00191810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7557974">Kottler et al. (1995)</a> demonstrated colocalization of GNRHR with the KIT gene (<a href="/entry/164920">164920</a>), which has been mapped to 4q12. <a href="#13" class="mim-tip-reference" title="Kakar, S. S., Neill, J. D. <strong>The human gonadotropin-releasing hormone receptor gene (GNRHR) maps to chromosome band 4q13.</strong> Cytogenet. Cell Genet. 70: 211-214, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789173</a>] [<a href="https://doi.org/10.1159/000134035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789173">Kakar and Neill (1995)</a> mapped the gene to 4q13 by PCR analysis of genomic DNA from human/hamster somatic cell hybrids combined with fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7789173+7557974" 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>The growth of sex hormone-dependent tumors is inhibited by analogs of luteinizing hormone-releasing hormone (LHRH; <a href="/entry/152760">152760</a>). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency. In addition, LHRH agonists and antagonists exert a direct effect on these tumors that probably is mediated by specific high-affinity LHRH receptors found on these cells. LHRH agonists and antagonists also suppress the growth of experimental pancreatic cancers. <a href="#34" class="mim-tip-reference" title="Szende, B., Srkalovic, G., Timar, J., Mulchahey, J. J., Neill, J. D., Lapis, K., Csikos, A., Szepeshazi, K., Schally, A. V. <strong>Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.</strong> Proc. Nat. Acad. Sci. 88: 4153-4156, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1851995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1851995</a>] [<a href="https://doi.org/10.1073/pnas.88.10.4153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1851995">Szende et al. (1991)</a> demonstrated that pancreatic tumor cells exhibit high-affinity binding sites for LHRH, but only in their nuclei; low-affinity sites are associated with the cell membranes. These binding sites appear to be LHRH receptors since electron microscopic immunohistochemical studies show that an antibody to the LHRH receptor reacted with sites in the nucleus of pancreatic tumor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1851995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., Riek, R. <strong>Functional amyloids as natural storage of peptide hormones in pituitary secretory granules.</strong> Science 325: 328-332, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19541956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19541956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19541956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1173155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19541956">Maji et al. (2009)</a> found that peptide and protein hormones, including GNRH, in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation, and concluded that functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19541956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a sister and brother with normosmic idiopathic hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#6" class="mim-tip-reference" title="de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. <strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong> New Eng. J. Med. 337: 1597-1602, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>] [<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371856">de Roux et al. (1997)</a> identified compound heterozygosity for 2 missense mutations in the GNRHR gene (Q106R, <a href="#0001">138850.0001</a> and R262Q, <a href="#0002">138850.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9371856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Layman, L. C., Cohen, D. P., Jin, M., Xie, J., Li, Z., Reindollar, R. H., Bolbolan, S., Bick, D. P., Sherins, R. R., Duck, L. W., Musgrove, L. C., Sellers, J. C., Neill, J. D. <strong>Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. (Letter)</strong> Nature Genet. 18: 14-15, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425890</a>] [<a href="https://doi.org/10.1038/ng0198-14" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425890">Layman et al. (1998)</a> screened 46 unrelated patients with normosmic idiopathic HH for GNRHR mutations and identified compound heterozygosity for the R262Q mutation and another missense mutation (Y284C; <a href="#0003">138850.0003</a>) in 1 family with 4 affected sibs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425890" 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 3 sibs from a kindred with isolated HH, <a href="#3" class="mim-tip-reference" title="Caron, P., Chauvin, S., Christin-Maitre, S., Bennet, A., Lahlou, N., Counis, R., Bouchard, P., Kottler, M.-L. <strong>Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.</strong> J. Clin. Endocr. Metab. 84: 990-996, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084584</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084584">Caron et al. (1999)</a> identified compound heterozygosity for R262Q and another missense mutation in the GNRHR gene (A129D; <a href="#0004">138850.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084584" 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="Kottler, M.-L., Counis, R., Bouchard, P. <strong>Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.</strong> Arch. Med. Res. 30: 481-485, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10714361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10714361</a>] [<a href="https://doi.org/10.1016/s0188-4409(99)00072-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10714361">Kottler et al. (1999)</a> analyzed in detail the GNRHR mutations in 7 independent familial and sporadic cases of idiopathic hypogonadotropic hypogonadism reported to that time. The Q106R and R262Q mutations were frequent in patients from all geographic areas (North and South America and Europe). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10714361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a brother and 2 sisters with HH, <a href="#5" class="mim-tip-reference" title="de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G. <strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong> J. Clin. Endocr. Metab. 84: 567-572, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10022417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10022417</a>] [<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10022417">de Roux et al. (1999)</a> identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene; in addition, all 3 sibs carried another GNRHR missense mutation (S217R; <a href="#0005">138850.0005</a>) on the same allele with Q106R. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10022417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male patient with complete HH, <a href="#29" class="mim-tip-reference" title="Pralong, F. P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M. L., Portmann, L., Gaillard, R. C. <strong>Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.</strong> J. Clin. Endocr. Metab. 84: 3811-3816, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10523035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10523035</a>] [<a href="https://doi.org/10.1210/jcem.84.10.6042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10523035">Pralong et al. (1999)</a> identified homozygosity for a missense mutation in GNRHR (S168R; <a href="#0006">138850.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10523035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a woman with complete HH, <a href="#16" class="mim-tip-reference" title="Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R. <strong>A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.</strong> J. Clin. Endocr. Metab. 85: 3002-3008, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999776</a>] [<a href="https://doi.org/10.1210/jcem.85.9.6783" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10999776">Kottler et al. (2000)</a> identified compound heterozygosity for Q106R and a nonsense mutation in the GNRHR gene (L314X; <a href="#0007">138850.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10999776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 26-year-old male with a mild form of hypogonadotropic hypogonadism, <a href="#27" class="mim-tip-reference" title="Pitteloud, N., Boepple, P. A., DeCruz, S., Valkenburgh, S. B., Crowley, W. F., Jr., Hayes, F. J. <strong>The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.</strong> J. Clin. Endocr. Metab. 86: 2470-2475, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397842</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7542" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397842">Pitteloud et al. (2001)</a> identified homozygosity for the R262Q mutation in the GNRHR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397842" 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="Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C. <strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong> J. Clin. Endocr. Metab. 86: 2680-2686, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397871</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397871">Costa et al. (2001)</a> investigated 17 Brazilian patients with normosmic HH and identified homozygosity for a GNRHR missense mutation (R139H; <a href="#0008">138850.0008</a>) in a female with complete HH and compound heterozygosity for Q106R and another GNRHR missense mutation (N10K; <a href="#0009">138850.0009</a>) in 3 sibs with partial HH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397871" 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>To determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with idiopathic hypogonadotropic hypogonadism, <a href="#2" class="mim-tip-reference" title="Beranova, M., Oliveira, L. M. B., Bedecarrats, G. Y., Schipani, E., Vallejo, M., Ammini, A. C., Quintos, J. B., Hall, J. E., Martin, K. A., Hayes, F. J., Pitteloud, N., Kaiser, U. B., Crowley, W. F., Jr., Seminara, S. B. <strong>Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 86: 1580-1588, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11297587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11297587</a>] [<a href="https://doi.org/10.1210/jcem.86.4.7395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11297587">Beranova et al. (2001)</a> screened 108 probands with idiopathic hypogonadotropic hypogonadism for mutations in the coding sequence of GNRHR. Forty-eight of the 108 patients had a normal sense of smell, whereas the remaining 60 had anosmia or hyposmia (Kallmann syndrome). Five unrelated probands (3 men and 2 women), all normosmic, were documented to have changes in the coding sequence of the GNRHR. Two of these probands were from a subgroup of 5 kindreds consistent with a recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5 (40%) in patients with normosmic, autosomal recessive idiopathic hypogonadotropic hypogonadism. The remaining 3 probands with GNRHR mutations were from a subgroup of 18 patients without evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in patients with sporadic idiopathic hypogonadotropic hypogonadism and a normal sense of smell. Among the 5 individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted, including testicular sizes that varied from prepubertal to the normal adult male range. Three probands had compound heterozygous mutations, and 2 had homozygous mutations. Of the 8 DNA sequence changes identified, 4 were novel. COS-7 cells transiently transfected with cDNAs encoding the human GNRHR containing each of these 4 novel mutations failed to respond to GNRH agonist stimulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11297587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Janovick, J. A., Maya-Nunez, G., Conn, P. M. <strong>Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target.</strong> J. Clin. Endocr. Metab. 87: 3255-3262, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107234</a>] [<a href="https://doi.org/10.1210/jcem.87.7.8582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107234">Janovick et al. (2002)</a> showed pharmacologic rescue, assessed by ligand binding and restoration of receptor coupling to effector, of 5 naturally occurring GNRHR mutants identified from patients with hypogonadotropic hypogonadism, as well as rescue of other defective receptors manufactured with internal or terminal deletions or substitutions at sites expected to be involved in establishment of tertiary receptor structure. The pharmacologic agent used was a small, membrane-permeant molecule, originally designed as an orally active, nonpeptide receptor antagonist, but is believed to function as a folding template, capable of correcting the structural defects caused by the mutations and thereby restoring function. The rescued receptor, stabilized in the plasma membrane, coupled ligand binding to activation of the appropriate effector system. For comparison, low-, intermediate-, or high-affinity peptide antagonists of GNRHR (that do not penetrate the cell) were unable to effect rescue, as was a nonbinding peptidomimetic congener of the rescue agent; this latter effect demonstrates specificity of the rescue agent. <a href="#10" class="mim-tip-reference" title="Janovick, J. A., Maya-Nunez, G., Conn, P. M. <strong>Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target.</strong> J. Clin. Endocr. Metab. 87: 3255-3262, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107234</a>] [<a href="https://doi.org/10.1210/jcem.87.7.8582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107234">Janovick et al. (2002)</a> concluded that mutant GNRHRs frequently have not lost intrinsic functionality and are subject to rescue by techniques that enhance membrane expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107234" 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="#1" class="mim-tip-reference" title="Bedecarrats, G. Y., Linher, K. D., Kaiser, U. B. <strong>Two common naturally occurring mutations in the human gonadotropin-releasing hormone (GnRH) receptor have differential effects on gonadotropin gene expression and on GnRH-mediated signal transduction.</strong> J. Clin. Endocr. Metab. 88: 834-843, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574221</a>] [<a href="https://doi.org/10.1210/jc.2002-020806" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574221">Bedecarrats et al. (2003)</a> analyzed 2 common mutations in GNRHR, gln106 to arg (Q106R; <a href="#0001">138850.0001</a>) and arg262 to gln (R262Q; <a href="#0002">138850.0002</a>), for their effects on the stimulation of gonadotropin subunit and GNRHR gene expression by GNRH. Despite similar impairment of GNRH-stimulated inositol phosphate production, dose-response analyses indicated that Q106R and R262Q both reduced the sensitivity of the FSH-beta (<a href="/entry/136530">136530</a>) gene promoter to a greater extent than LH-beta (<a href="/entry/152780">152780</a>) or the alpha-glycoprotein subunit (alpha-GSU; <a href="/entry/118850">118850</a>), suggesting the involvement of more than one signaling pathway. Furthermore, although the sensitivities of the LH-beta and FSH-beta gene promoters to GNRH were similarly affected by both mutants, alpha-GSU sensitivity was decreased to a greater extent by R262Q than by Q106R. Similarly, GNRHR gene promoter sensitivity was significantly reduced only by R262Q. The authors concluded that differential stimulation of LH-beta, FSH-beta, and alpha-GSU gene expression may contribute to the varied phenotypes observed among patients harboring these mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Leanos-Miranda, A., Ulloa-Aguirre, A., Ji, T. H., Janovick, J. A., Conn, P. M. <strong>Dominant-negative action of disease-causing gonadotropin-releasing hormone receptor (GnRHR) mutants: a trait that potentially coevolved with decreased plasma membrane expression of GnRHR in humans.</strong> J. Clin. Endocr. Metab. 88: 3360-3367, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12843188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12843188</a>] [<a href="https://doi.org/10.1210/jc.2003-030084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12843188">Leanos-Miranda et al. (2003)</a> demonstrated that GNRHR mutants inhibited the function of wildtype GNRHR, measured by activation of effector and ligand binding. Inhibition varied depending on the particular GNRHR mutant coexpressed and the ratio of GNRHR mutant to wildtype GNRHR cDNA cotransfected. The GNRHR mutants did not interfere with the function of genetically modified GNRHRs bearing either a deletion of primate-specific lys191 or the carboxyl-terminal tail of catfish GNRHR. The dominant-negative effect of the naturally occurring receptor mutants occurred only for the wildtype GNRHR, which has intrinsic low maturation efficiency. The data suggested that this dominant-negative effect accompanies the diminished plasma membrane expression as a recent evolutionary event. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12843188" 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>To determine whether genetic variation within either the GNRHR or GNRH1 genes contributes to the regulation of pubertal timing in the general population, <a href="#30" class="mim-tip-reference" title="Sedlmeyer, I. L., Pearce, C. L., Trueman, J. A., Butler, J. L., Bersaglieri, T., Read, A. P., Clayton, P. E., Kolonel, L. N., Henderson, B. E., Hirschhorn, J. N., Palmert, M. R. <strong>Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing.</strong> J. Clin. Endocr. Metab. 90: 1091-1099, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15546906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15546906</a>] [<a href="https://doi.org/10.1210/jc.2004-0649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15546906">Sedlmeyer et al. (2005)</a> performed sequence analysis and haplotype-based association studies in individuals with later than average pubertal development. All observed associations were relatively modest and only nominally statistically significant. The authors concluded that genetic variation in GHRH1 and GNRHR is not likely to be a substantial modulator of pubertal timing in the general population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15546906" 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>Oligogenic Inheritance</em></strong></p><p>
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In 2 sisters with primary amenorrhea and no breast development at 25 and 18 years of age, respectively (<a href="/entry/146110">146110</a>), <a href="#31" class="mim-tip-reference" title="Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E. <strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong> J. Clin. Endocr. Metab. 85: 556-562, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10690855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10690855</a>] [<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10690855">Seminara et al. (2000)</a> identified compound heterozygosity for Q106R on one allele and R262Q (<a href="#0002">138850.0002</a>) on the other. The apparently unaffected parents were heterozygous for the mutations. <a href="#28" class="mim-tip-reference" title="Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr. <strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 117: 457-463, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17235395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17235395</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17235395[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI29884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17235395">Pitteloud et al. (2007)</a> reexamined the family studied by <a href="#31" class="mim-tip-reference" title="Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E. <strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong> J. Clin. Endocr. Metab. 85: 556-562, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10690855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10690855</a>] [<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10690855">Seminara et al. (2000)</a> and identified heterozygosity for an additional missense mutation in the FGFR1 gene (<a href="/entry/136350#0016">136350.0016</a>) in the 2 sisters and in their father, who had a history of delayed puberty. Mutation analysis of the children of the younger sister revealed that her unaffected daughter, who had undergone normal puberty, was heterozygous for the mutation in FGFR1 but had no mutations in the GNRHR gene, and that her prepubertal 10-year-old twin sons, born without cryptorchidism or microphallus, were each heterozygous for 1 of the mutations in GNRHR but did not have any mutations in the FGFR1 gene. <a href="#28" class="mim-tip-reference" title="Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr. <strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 117: 457-463, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17235395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17235395</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17235395[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI29884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17235395">Pitteloud et al. (2007)</a> concluded that defects in 2 different genes can synergize to produce a more severe phenotype in families with hypogonadotropic hypogonadism than either alone, and that this digenic model may account for some of the phenotypic heterogeneity seen in GnRH deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17235395+10690855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893836 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893836;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/rs104893836?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893836" 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=rs104893836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a sister and brother with hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#6" class="mim-tip-reference" title="de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. <strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong> New Eng. J. Med. 337: 1597-1602, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>] [<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371856">de Roux et al. (1997)</a> identified compound heterozygosity for a 317G-A transition in the GNRHR gene, resulting in a gln106-to-arg (Q106R) substitution, and a 785G-A transition, resulting in an arg262-to-gln (R262Q; <a href="#0002">138850.0002</a>) substitution. Both residues are highly conserved and are located in the first extracellular and third intracellular loop of the GNRH receptor, respectively. The unaffected parents and sister, who were clinically and endocrinologically normal, were each heterozygous for 1 of the mutations. Functional analysis demonstrated that GNRH binding was markedly reduced, but not eliminated, with the Q106R mutant, whereas GNRH binding was similar to wildtype with the R262Q mutant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9371856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a brother and 2 sisters with HH, <a href="#5" class="mim-tip-reference" title="de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G. <strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong> J. Clin. Endocr. Metab. 84: 567-572, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10022417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10022417</a>] [<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10022417">de Roux et al. (1999)</a> identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene; in addition, all 3 sibs carried another GNRHR missense mutation (S217R; <a href="#0005">138850.0005</a>) on the same allele with Q106R. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10022417" 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 2 sisters with primary amenorrhea and no breast development at 25 and 18 years of age, respectively, <a href="#31" class="mim-tip-reference" title="Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E. <strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong> J. Clin. Endocr. Metab. 85: 556-562, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10690855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10690855</a>] [<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10690855">Seminara et al. (2000)</a> identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene. The apparently unaffected parents were heterozygous for the mutations. <a href="#28" class="mim-tip-reference" title="Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr. <strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 117: 457-463, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17235395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17235395</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17235395[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI29884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17235395">Pitteloud et al. (2007)</a> reexamined this family and identified heterozygosity for an additional missense mutation in the FGFR1 gene (<a href="/entry/136350#0016">136350.0016</a>) in the 2 sisters and in their father, who had a history of delayed puberty. Mutation analysis of the children of the younger sister revealed that her unaffected daughter, who underwent normal puberty, was heterozygous for the mutation in FGFR1 but had no mutations in the GNRHR gene, and that her prepubertal 10-year-old twin sons, born without cryptorchidism or microphallus, were each heterozygous for 1 of the mutations in the GNRHR gene but did not have any mutations in the FGFR1 gene. <a href="#28" class="mim-tip-reference" title="Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr. <strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 117: 457-463, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17235395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17235395</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17235395[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI29884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17235395">Pitteloud et al. (2007)</a> concluded that defects in 2 different genes can synergize to produce a more severe phenotype in families with hypogonadotropic hypogonadism than either alone, and that this digenic model may account for some of the phenotypic heterogeneity seen in GnRH deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17235395+10690855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a woman with complete HH, <a href="#16" class="mim-tip-reference" title="Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R. <strong>A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.</strong> J. Clin. Endocr. Metab. 85: 3002-3008, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999776</a>] [<a href="https://doi.org/10.1210/jcem.85.9.6783" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10999776">Kottler et al. (2000)</a> identified compound heterozygosity for Q106R and a nonsense mutation in the GNRHR gene (L314X; <a href="#0007">138850.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10999776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 26-year-old male with mild HH, who had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and normal testicular size, and who developed sperm after treatment with CG (see <a href="/entry/118860">118860</a>), <a href="#27" class="mim-tip-reference" title="Pitteloud, N., Boepple, P. A., DeCruz, S., Valkenburgh, S. B., Crowley, W. F., Jr., Hayes, F. J. <strong>The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.</strong> J. Clin. Endocr. Metab. 86: 2470-2475, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397842</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7542" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397842">Pitteloud et al. (2001)</a> identified homozygosity for the Q106R mutation in the GNRHR gene. The authors noted that <a href="#6" class="mim-tip-reference" title="de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. <strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong> New Eng. J. Med. 337: 1597-1602, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>] [<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371856">de Roux et al. (1997)</a> had previously shown that GNRH binding is decreased, but not eliminated, with the Q106R mutant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11397842+9371856" 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 4 Brazilian sibs with partial HH, <a href="#4" class="mim-tip-reference" title="Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C. <strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong> J. Clin. Endocr. Metab. 86: 2680-2686, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397871</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397871">Costa et al. (2001)</a> identified compound heterozygosity for Q106R and another missense mutation in the GNRHR gene (N10K; <a href="#0009">138850.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397871" 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 2 brothers with severe HH, <a href="#14" class="mim-tip-reference" title="Karges, B., Karges, W., Mine, M., Ludwig, L., Kuhne, R., Milgrom, E., de Roux, N. <strong>Mutation ala(171)thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 88: 1873-1879, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679486</a>] [<a href="https://doi.org/10.1210/jc.2002-020005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12679486">Karges et al. (2003)</a> identified compound heterozygosity for Q106R and another missense mutation in the GNRHR gene (A171T; <a href="#0012">138850.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893837 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893837;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/rs104893837?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893837" 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=rs104893837" 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=RCV000030908 OR RCV000494391 OR RCV001849268 OR RCV004584328 OR RCV004782017" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030908, RCV000494391, RCV001849268, RCV004584328, RCV004782017" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030908...</a>
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<p>For discussion of the arg262-to-gln (R262Q) mutation in the GNRHR gene that was found in compound heterozygous state in patients with hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>) by <a href="#6" class="mim-tip-reference" title="de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. <strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong> New Eng. J. Med. 337: 1597-1602, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>] [<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371856">de Roux et al. (1997)</a> and <a href="#31" class="mim-tip-reference" title="Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E. <strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong> J. Clin. Endocr. Metab. 85: 556-562, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10690855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10690855</a>] [<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10690855">Seminara et al. (2000)</a>, see <a href="#0001">138850.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9371856+10690855" 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 R262Q mutation in GNRHR was also found in compound heterozygous state in 4 sibs with HH by <a href="#18" class="mim-tip-reference" title="Layman, L. C., Cohen, D. P., Jin, M., Xie, J., Li, Z., Reindollar, R. H., Bolbolan, S., Bick, D. P., Sherins, R. R., Duck, L. W., Musgrove, L. C., Sellers, J. C., Neill, J. D. <strong>Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. (Letter)</strong> Nature Genet. 18: 14-15, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425890</a>] [<a href="https://doi.org/10.1038/ng0198-14" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425890">Layman et al. (1998)</a> (see <a href="#0003">138850.0003</a>) and in 3 sibs with HH by <a href="#3" class="mim-tip-reference" title="Caron, P., Chauvin, S., Christin-Maitre, S., Bennet, A., Lahlou, N., Counis, R., Bouchard, P., Kottler, M.-L. <strong>Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.</strong> J. Clin. Endocr. Metab. 84: 990-996, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084584</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084584">Caron et al. (1999)</a> (see <a href="#0004">138850.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9425890+10084584" 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="de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G. <strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong> J. Clin. Endocr. Metab. 84: 567-572, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10022417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10022417</a>] [<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10022417">De Roux et al. (1999)</a> found the R262Q mutation in compound heterozygous state in 3 sibs with HH, who carried both the Q106R (<a href="#0001">138850.0001</a>) and S217R (<a href="#0005">138850.0005</a>) mutations on the other allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10022417" 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 2 brothers with HH7, <a href="#21" class="mim-tip-reference" title="Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C. <strong>A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia.</strong> J. Clin. Endocr. Metab. 91: 5117-5121, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16968799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16968799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16968799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2006-0807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16968799">Lin et al. (2006)</a> identified homozygosity for the R262Q mutation in the GNRHR gene. The proband, who presented at 15 years of age with delayed puberty, responded to a short course of testosterone with appropriate progress through puberty, whereas his younger brother showed little response after treatment. <a href="#21" class="mim-tip-reference" title="Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C. <strong>A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia.</strong> J. Clin. Endocr. Metab. 91: 5117-5121, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16968799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16968799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16968799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2006-0807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16968799">Lin et al. (2006)</a> concluded that homozygous partial loss-of-function mutations in GNRHR, such as R262Q, can cause variable phenotypes, including apparent delayed puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16968799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28933074 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933074;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/rs28933074?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933074" 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=rs28933074" 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=RCV000030909" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030909" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030909</a>
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<p>In 4 sibs with hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#18" class="mim-tip-reference" title="Layman, L. C., Cohen, D. P., Jin, M., Xie, J., Li, Z., Reindollar, R. H., Bolbolan, S., Bick, D. P., Sherins, R. R., Duck, L. W., Musgrove, L. C., Sellers, J. C., Neill, J. D. <strong>Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. (Letter)</strong> Nature Genet. 18: 14-15, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425890</a>] [<a href="https://doi.org/10.1038/ng0198-14" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425890">Layman et al. (1998)</a> identified compound heterozygosity for the R262Q mutation in the GNRHR gene (<a href="#0002">138850.0002</a>) and an A-G transition resulting in a tyr284-to-cys (Y284C; <a href="#0003">138850.0003</a>) substitution in transmembrane region 6. The mutations were not found in an unaffected sib or in 75 unrelated controls. At least 1 of the affected females ovulated in response to exogenous gonadotropins. The 2 GNRHR mutations had minimal effects on receptor affinity, but receptor expression was decreased for both. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893838 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893838;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/rs104893838?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893838" 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=rs104893838" 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=RCV000030910 OR RCV001851889" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030910, RCV001851889" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030910...</a>
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<p>In 3 sibs with isolated hypogonadotropic hypogonadism (HH7; 146110), <a href="#3" class="mim-tip-reference" title="Caron, P., Chauvin, S., Christin-Maitre, S., Bennet, A., Lahlou, N., Counis, R., Bouchard, P., Kottler, M.-L. <strong>Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.</strong> J. Clin. Endocr. Metab. 84: 990-996, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084584</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084584">Caron et al. (1999)</a> identified compound heterozygosity for the R262Q mutation in the GNRHR gene (<a href="#0002">138850.0002</a>) and a 386C-A transversion, resulting in an ala129-to-asp (A129D) substitution. Their unaffected parents were each heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893839 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893839;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=rs104893839" 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=rs104893839" 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=RCV000030911" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030911" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030911</a>
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<p>For discussion of the ser217-to-arg (S217R) mutation in the GNRHR gene that was found in compound heterozygous state in 3 sibs with hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>) by <a href="#5" class="mim-tip-reference" title="de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G. <strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong> J. Clin. Endocr. Metab. 84: 567-572, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10022417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10022417</a>] [<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10022417">de Roux et al. (1999)</a>, see <a href="#0001">138850.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10022417" 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 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</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">rs104893840 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893840;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=rs104893840" 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=rs104893840" 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=RCV000030912 OR RCV001849269" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030912, RCV001849269" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030912...</a>
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<p><a href="#29" class="mim-tip-reference" title="Pralong, F. P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M. L., Portmann, L., Gaillard, R. C. <strong>Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.</strong> J. Clin. Endocr. Metab. 84: 3811-3816, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10523035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10523035</a>] [<a href="https://doi.org/10.1210/jcem.84.10.6042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10523035">Pralong et al. (1999)</a> described a male patient with complete hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>) who presented primary failure of pulsatile GNRH (<a href="/entry/152760">152760</a>) therapy, but responded to exogenous gonadotropin administration. The patient had a T-to-A transversion at codon 168 of the gene encoding the GNRH receptor (GNRHR), resulting in a ser168-to-arg (S168R) change in the fourth transmembrane domain of GNRHR. This mutation was present in homozygous state in the patient, whereas it was in heterozygous state in both phenotypically normal parents. When introduced into GNRHR cDNA, S168R resulted in complete loss of the receptor-mediated signaling response to GNRH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10523035" 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 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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GNRHR, LEU314TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893841 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893841;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=rs104893841" 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=rs104893841" 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=RCV000030913" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030913" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030913</a>
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<p>In a woman with complete hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#16" class="mim-tip-reference" title="Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R. <strong>A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.</strong> J. Clin. Endocr. Metab. 85: 3002-3008, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999776</a>] [<a href="https://doi.org/10.1210/jcem.85.9.6783" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10999776">Kottler et al. (2000)</a> identified compound heterozygosity for 2 mutations in the GNRHR gene: the Q106R mutation (<a href="#0001">138850.0001</a>) and a leu314-to-ter (L314X) substitution, resulting in partial deletion of the seventh transmembrane domain. The L314X mutant receptor showed neither measurable binding nor inositol phosphate production when transfected in CHO-K1 cells compared to the wildtype receptor. Family members who were heterozygous for either mutation had normal pubertal development and fertility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10999776" 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 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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GNRHR, ARG139HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893842 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893842;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/rs104893842?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893842" 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=rs104893842" 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=RCV000030914 OR RCV000203470 OR RCV000497820" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030914, RCV000203470, RCV000497820" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030914...</a>
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<p>In a Brazilian woman with complete hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#4" class="mim-tip-reference" title="Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C. <strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong> J. Clin. Endocr. Metab. 86: 2680-2686, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397871</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397871">Costa et al. (2001)</a> identified homozygosity for an arg139-to-his (R139H) substitution located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GNRHR gene. The R139H mutation completely eliminated detectable GNRH-binding activity and prevented GNRH-induced stimulation of inositol phosphate accumulation in vitro. The patient had undetectable serum basal LH and FSH levels that failed to respond to GNRH stimulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397871" 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 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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GNRHR, ASN10LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893843 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893843;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/rs104893843?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893843" 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=rs104893843" 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=RCV000030915 OR RCV000375229" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030915, RCV000375229" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030915...</a>
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<p>In 4 Brazilian sibs with partial hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), who had low serum basal LH levels that were responsive to GNRH stimulation, <a href="#4" class="mim-tip-reference" title="Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C. <strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong> J. Clin. Endocr. Metab. 86: 2680-2686, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397871</a>] [<a href="https://doi.org/10.1210/jcem.86.6.7551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11397871">Costa et al. (2001)</a> identified compound heterozygosity for the Q106R mutation in the GNRHR gene (<a href="#0001">138850.0001</a>) and an asn10-to-lys (N10K; <a href="#0009">138850.0009</a>) substitution in the extracellular amino-terminal domain. The Q106R mutation had been shown by <a href="#6" class="mim-tip-reference" title="de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. <strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong> New Eng. J. Med. 337: 1597-1602, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>] [<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371856">de Roux et al. (1997)</a> to bind GNRH with reduced affinity, and in vitro analysis also demonstrated decreased affinity for GNRH with the N10K mutant compared to wildtype GNRHR. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9371856+11397871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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GNRHR, GLU90LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893844 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893844;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/rs104893844?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893844" 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=rs104893844" 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=RCV000030916 OR RCV001560549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030916, RCV001560549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030916...</a>
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<p>In 2 sibs with the complete form of hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#33" class="mim-tip-reference" title="Soderlund, D., Canto, P., de la Chesnaye, E., Ulloa-Aguirre, A., Mendez, J. P. <strong>A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene.</strong> Clin. Endocr. 54: 493-498, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11318785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11318785</a>] [<a href="https://doi.org/10.1046/j.1365-2265.2001.01211.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11318785">Soderlund et al. (2001)</a> detected a novel homozygous G-to-A transition at nucleotide 268 of the GNRHR gene, which resulted in a glu90-to-lys (E90K) amino acid substitution. This mutation is located in the second transmembrane domain of the GNRH receptor. To assess the functional role of E90, <a href="#24" class="mim-tip-reference" title="Maya-Nunez, G., Janovick, J. A., Ulloa-Aguirre, A., Soderlund, D., Conn, P. M., Mendez, J. P. <strong>Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E90K) GnRH receptor function by a deletion at a distant site.</strong> J. Clin. Endocr. Metab. 87: 2144-2149, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994356</a>] [<a href="https://doi.org/10.1210/jcem.87.5.8386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994356">Maya-Nunez et al. (2002)</a> performed mutation analysis of the E90K substitution. Transient expression of the mutant receptor in COS-7 cells resulted in a virtual abolition of GNRH agonist binding and agonist-stimulated phosphoinositide turnover, initially suggesting that E90 may be essential for GNRH binding. To examine the role of a site known to suppress GNRHR function, mutants with deletion of K191 from the GNRHR and/or addition of catfish Gnrhr intracellular C-terminal tail to GNRHR were prepared. Activation of intracellular signaling in response to buserelin was restored by deletion of K191 from the E90K mutant receptor but minimally by addition of the catfish GNRHR C-terminal tail. This study provided evidence that the E90K mutation impairs GNRHR-effector coupling. <a href="#24" class="mim-tip-reference" title="Maya-Nunez, G., Janovick, J. A., Ulloa-Aguirre, A., Soderlund, D., Conn, P. M., Mendez, J. P. <strong>Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E90K) GnRH receptor function by a deletion at a distant site.</strong> J. Clin. Endocr. Metab. 87: 2144-2149, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994356</a>] [<a href="https://doi.org/10.1210/jcem.87.5.8386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994356">Maya-Nunez et al. (2002)</a> concluded that the observation that sequence modifications that enhance surface expression of the receptor restore function presents the possibility that loss of surface expression may underlie the severe phenotype exhibited by hypogonadotropic hypogonadism patients bearing this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11318785+11994356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797044452 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044452;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=rs797044452" 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=rs797044452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a woman with complete GNRH resistance (HH7; <a href="/entry/146110">146110</a>), <a href="#32" class="mim-tip-reference" title="Silveira, L. F. G., Stewart, P. M., Thomas, M., Clark, D. A., Bouloux, P. M. G., MacColl, G. S. <strong>Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR 'knockout'.</strong> J. Clin. Endocr. Metab. 87: 2973-2977, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050282</a>] [<a href="https://doi.org/10.1210/jcem.87.6.8535" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12050282">Silveira et al. (2002)</a> identified homozygosity for a G-A transition at the intron 1/exon 2 boundary. RT-PCR analysis of RNA showed a transcript lacking all of exon 2, with splicing of exon 1 to exon 3 and creation of a frameshift, generating a coding sequence for 3 new amino acids followed by a stop codon. Although it was not clear whether the mutant receptor was actually expressed, the resultant mRNA sequence was presumed to produce a truncated receptor with no binding or signaling capacity. The proband presented with primary amenorrhea and absent thelarche and pubarche. Dynamic tests demonstrated absent spontaneous gonadotropin pulsatility, and there was no response to either exogenous pulsatile or acute GNRH administration. However, the patient responded to exogenous gonadotropin administration with a resulting normal pregnancy. Her unaffected sister was heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050282" 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>.0012 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74452732 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74452732;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/rs74452732?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74452732" 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=rs74452732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 brothers with severe hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>), <a href="#14" class="mim-tip-reference" title="Karges, B., Karges, W., Mine, M., Ludwig, L., Kuhne, R., Milgrom, E., de Roux, N. <strong>Mutation ala(171)thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 88: 1873-1879, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679486</a>] [<a href="https://doi.org/10.1210/jc.2002-020005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12679486">Karges et al. (2003)</a> identified compound heterozygosity for 2 mutations in the GNRHR gene: Q106R (<a href="#0001">138850.0001</a>) and a 511G-A transition that results in an ala171-to-thr (A171T) substitution at transmembrane helix 4 (TMH4). After in vitro expression in human embryonic kidney 293T cells, the A171T mutant LHCGR exhibited a lack of phospholipase C activity in signal transduction. Specific receptor binding of radioisotope-labeled GNRH ligand was undetectable in transfected cells. Molecular modeling and dynamic simulation of the mutant receptor suggested the introduction of a stable hydrogen bond that impeded conformational mobility of the TMH3 and TMH4 domains required for sequential ligand binding and receptor activation, thus stabilizing the LHCGR in its inactive conformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</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">rs281865427 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865427;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=rs281865427" 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=rs281865427" 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=RCV000030915 OR RCV000030919 OR RCV000375229 OR RCV000498552" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030915, RCV000030919, RCV000375229, RCV000498552" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030915...</a>
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<p><a href="#25" class="mim-tip-reference" title="Meysing, A. U., Kanasaki, H., Bedecarrats, G. Y., Acierno, J. S., Jr., Conn, P. M., Martin, K. A., Seminara, S. B., Hall, J. E., Crowley, W. F., Jr., Kaiser, U. B. <strong>GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone.</strong> J. Clin. Endocr. Metab. 89: 3189-3198, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15240592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15240592</a>] [<a href="https://doi.org/10.1210/jc.2003-031808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15240592">Meysing et al. (2004)</a> reported a normosmic woman with congenital idiopathic hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>) in whom treatment with pulsatile GNRH resulted in an unusual response. The woman not only required an increased dose of pulsatile GNRH for ovarian follicular development, but LH secretion did not increase appropriately, estradiol levels remained low, and she did not ovulate spontaneously. Sequencing of the GNRHR coding sequence revealed compound heterozygosity for a 30T-A transversion in exon 1 of the GNRHR gene, resulting in a 2-amino acid substitution on one allele (N10K+Q11K), and a missense mutation on the other allele (P320L; <a href="#0014">138850.0014</a>). Introduction of the P320L mutation into the GNRH receptor led to failure of detectable ligand binding and failure of stimulation of inositol phosphate production and gonadotropin subunit gene promoter activity in response to GnRH in transiently transfected cells. Introduction of the N10K+Q11K mutation into the GNRH receptor resulted in reduced binding of a GNRH agonist to 25% of the wildtype receptor. In addition, the EC50 value for GNRH stimulation of inositol phosphate production was significantly increased, and the dose-response curves for stimulation of alpha-gonadotropin subunit (<a href="/entry/118850">118850</a>), LH-beta (<a href="/entry/152780">152780</a>), and FSH-beta (<a href="/entry/136530">136530</a>) gene transcription by GNRH were similarly shifted to the right. The authors proposed that these GNRHR mutations result in a rightward shift of the dose-response curves of gonadotropin responses to pulsatile GNRH in the subject and unmask the differential sensitivities of LH and FSH to GNRH, resulting in low LH and estradiol levels despite appropriate FSH secretion and follicular growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15240592" 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 pro320-to-leu (P320L) mutation in the GNRHR gene that was found in compound heterozygous state in a woman with hypogonadotropic hypogonadism (HH7; <a href="/entry/146110">146110</a>) by <a href="#25" class="mim-tip-reference" title="Meysing, A. U., Kanasaki, H., Bedecarrats, G. Y., Acierno, J. S., Jr., Conn, P. M., Martin, K. A., Seminara, S. B., Hall, J. E., Crowley, W. F., Jr., Kaiser, U. B. <strong>GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone.</strong> J. Clin. Endocr. Metab. 89: 3189-3198, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15240592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15240592</a>] [<a href="https://doi.org/10.1210/jc.2003-031808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15240592">Meysing et al. (2004)</a>, see <a href="#0013">138850.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15240592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Mason1986" class="mim-tip-reference" title="Mason, A. J., Hayflick, J. S., Zoeller, R. T., Young, W. S., III, Phillips, H. S., Nikolics, K., Seeburg, P. H. <strong>A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the 'hpg' mouse.</strong> Science 234: 1366-1371, 1986.">Mason et al. (1986)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Bedecarrats2003" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
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Bedecarrats, G. Y., Linher, K. D., Kaiser, U. B.
|
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<strong>Two common naturally occurring mutations in the human gonadotropin-releasing hormone (GnRH) receptor have differential effects on gonadotropin gene expression and on GnRH-mediated signal transduction.</strong>
|
|
J. Clin. Endocr. Metab. 88: 834-843, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jc.2002-020806" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
|
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<a id="Beranova2001" class="mim-anchor"></a>
|
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Beranova, M., Oliveira, L. M. B., Bedecarrats, G. Y., Schipani, E., Vallejo, M., Ammini, A. C., Quintos, J. B., Hall, J. E., Martin, K. A., Hayes, F. J., Pitteloud, N., Kaiser, U. B., Crowley, W. F., Jr., Seminara, S. B.
|
|
<strong>Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 86: 1580-1588, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11297587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11297587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11297587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.86.4.7395" target="_blank">Full Text</a>]
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|
|
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|
|
|
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<li>
|
|
<a id="3" class="mim-anchor"></a>
|
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<a id="Caron1999" class="mim-anchor"></a>
|
|
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|
|
Caron, P., Chauvin, S., Christin-Maitre, S., Bennet, A., Lahlou, N., Counis, R., Bouchard, P., Kottler, M.-L.
|
|
<strong>Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.</strong>
|
|
J. Clin. Endocr. Metab. 84: 990-996, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.84.3.5518" target="_blank">Full Text</a>]
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Costa2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C.
|
|
<strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2680-2686, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397871</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.86.6.7551" target="_blank">Full Text</a>]
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|
|
|
<li>
|
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<a id="5" class="mim-anchor"></a>
|
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<a id="de Roux1999" class="mim-anchor"></a>
|
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|
|
<p class="mim-text-font">
|
|
de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G.
|
|
<strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong>
|
|
J. Clin. Endocr. Metab. 84: 567-572, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10022417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10022417</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10022417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank">Full Text</a>]
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</li>
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|
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<li>
|
|
<a id="6" class="mim-anchor"></a>
|
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<a id="de Roux1997" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E.
|
|
<strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong>
|
|
New Eng. J. Med. 337: 1597-1602, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9371856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJM199711273372205" target="_blank">Full Text</a>]
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Fan1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fan, N. C., Jeung, E.-B., Peng, C., Olofsson, J. I., Krisinger, J., Leung, P. C. K.
|
|
<strong>The human gonadotropin-releasing hormone (GnRH) receptor gene: cloning, genomic organization and chromosomal assignment.</strong>
|
|
Molec. Cell. Endocr. 103: R1-R6, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7958384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7958384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7958384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0303-7207(94)90087-6" target="_blank">Full Text</a>]
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</p>
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|
|
</li>
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<li>
|
|
<a id="8" class="mim-anchor"></a>
|
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<a id="Fan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fan, N. C., Peng, C., Krisinger, J., Leung, P. C. K.
|
|
<strong>The human gonadotropin-releasing hormone receptor gene: complete structure including multiple promoters, transcription initiation sites, and polyadenylation signals.</strong>
|
|
Molec. Cell. Endocr. 107: R1-R8, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7768323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7768323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7768323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0303-7207(94)03460-b" target="_blank">Full Text</a>]
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Grosse1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grosse, R., Schoneberg, T., Schultz, G., Gudermann, T.
|
|
<strong>Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor.</strong>
|
|
Molec. Endocr. 11: 1305-1318, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1210/mend.11.9.9966" target="_blank">Full Text</a>]
|
|
|
|
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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
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<a id="Janovick2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janovick, J. A., Maya-Nunez, G., Conn, P. M.
|
|
<strong>Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target.</strong>
|
|
J. Clin. Endocr. Metab. 87: 3255-3262, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.87.7.8582" target="_blank">Full Text</a>]
|
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kaiser1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaiser, U. B., Dushkin, H., Altherr, M. R., Beier, D. R., Chin, W. W.
|
|
<strong>Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5.</strong>
|
|
Genomics 20: 506-508, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8034328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8034328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8034328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1994.1211" target="_blank">Full Text</a>]
|
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</p>
|
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|
|
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|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
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<a id="Kakar1992" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Kakar, S. S., Musgrove, L. C., Devor, D. C., Sellers, J. C., Neill, J. D.
|
|
<strong>Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 189: 289-295, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1333190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1333190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1333190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0006-291x(92)91556-6" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
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<a id="Kakar1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kakar, S. S., Neill, J. D.
|
|
<strong>The human gonadotropin-releasing hormone receptor gene (GNRHR) maps to chromosome band 4q13.</strong>
|
|
Cytogenet. Cell Genet. 70: 211-214, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000134035" target="_blank">Full Text</a>]
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|
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|
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|
|
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|
|
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|
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|
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|
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|
|
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|
|
<p class="mim-text-font">
|
|
Karges, B., Karges, W., Mine, M., Ludwig, L., Kuhne, R., Milgrom, E., de Roux, N.
|
|
<strong>Mutation ala(171)thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1873-1879, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1210/jc.2002-020005" target="_blank">Full Text</a>]
|
|
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|
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|
|
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|
|
|
|
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|
|
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|
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<a id="Kottler1995" class="mim-anchor"></a>
|
|
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|
|
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|
|
Kottler, M. L., Lorenzo, F., Bergametti, F., Commercon, P., Souchier, C., Counis, R.
|
|
<strong>Subregional mapping of the human gonadotropin-releasing hormone receptor (GnRH-R) gene to 4q between the markers D4S392 and D4S409.</strong>
|
|
Hum. Genet. 96: 477-480, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557974</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7557974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1007/BF00191810" target="_blank">Full Text</a>]
|
|
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|
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|
|
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|
|
|
|
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|
|
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|
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<a id="Kottler2000" class="mim-anchor"></a>
|
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|
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|
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Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R.
|
|
<strong>A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.</strong>
|
|
J. Clin. Endocr. Metab. 85: 3002-3008, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10999776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10999776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10999776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.9.6783" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Kottler1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kottler, M.-L., Counis, R., Bouchard, P.
|
|
<strong>Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.</strong>
|
|
Arch. Med. Res. 30: 481-485, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10714361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10714361</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10714361" 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/s0188-4409(99)00072-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Layman1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Layman, L. C., Cohen, D. P., Jin, M., Xie, J., Li, Z., Reindollar, R. H., Bolbolan, S., Bick, D. P., Sherins, R. R., Duck, L. W., Musgrove, L. C., Sellers, J. C., Neill, J. D.
|
|
<strong>Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. (Letter)</strong>
|
|
Nature Genet. 18: 14-15, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425890</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425890" 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/ng0198-14" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Leanos-Miranda2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leanos-Miranda, A., Ulloa-Aguirre, A., Ji, T. H., Janovick, J. A., Conn, P. M.
|
|
<strong>Dominant-negative action of disease-causing gonadotropin-releasing hormone receptor (GnRHR) mutants: a trait that potentially coevolved with decreased plasma membrane expression of GnRHR in humans.</strong>
|
|
J. Clin. Endocr. Metab. 88: 3360-3367, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12843188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12843188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12843188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-030084" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Leung1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leung, P. C. K., Squire, J., Peng, C., Fan, N., Hayden, M. R., Olofsson, J. I.
|
|
<strong>Mapping of the gonadotropin-releasing hormone (GnRH) receptor gene to human chromosome 4q21.2 by fluorescence in situ hybridization.</strong>
|
|
Mammalian Genome 6: 309-310, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7613048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7613048</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7613048" 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/BF00352431" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Lin2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C.
|
|
<strong>A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia.</strong>
|
|
J. Clin. Endocr. Metab. 91: 5117-5121, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16968799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16968799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16968799[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=16968799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2006-0807" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Maji2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., Riek, R.
|
|
<strong>Functional amyloids as natural storage of peptide hormones in pituitary secretory granules.</strong>
|
|
Science 325: 328-332, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19541956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19541956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19541956[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=19541956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1173155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Mason1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mason, A. J., Hayflick, J. S., Zoeller, R. T., Young, W. S., III, Phillips, H. S., Nikolics, K., Seeburg, P. H.
|
|
<strong>A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the 'hpg' mouse.</strong>
|
|
Science 234: 1366-1371, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3024317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3024317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3024317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3024317" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Maya-Nunez2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maya-Nunez, G., Janovick, J. A., Ulloa-Aguirre, A., Soderlund, D., Conn, P. M., Mendez, J. P.
|
|
<strong>Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E90K) GnRH receptor function by a deletion at a distant site.</strong>
|
|
J. Clin. Endocr. Metab. 87: 2144-2149, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.87.5.8386" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Meysing2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meysing, A. U., Kanasaki, H., Bedecarrats, G. Y., Acierno, J. S., Jr., Conn, P. M., Martin, K. A., Seminara, S. B., Hall, J. E., Crowley, W. F., Jr., Kaiser, U. B.
|
|
<strong>GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone.</strong>
|
|
J. Clin. Endocr. Metab. 89: 3189-3198, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15240592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15240592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15240592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-031808" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Morrison1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morrison, N., Sellar, R. E., Boyd, E., Eidne, K. A., Connor, J. M.
|
|
<strong>Assignment of the gene encoding the human gonadotropin-releasing hormone receptor to 4q13.2-13.3 by fluorescence in situ hybridization.</strong>
|
|
Hum. Genet. 93: 714-715, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8005601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8005601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8005601" 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/BF00201579" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Pitteloud2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pitteloud, N., Boepple, P. A., DeCruz, S., Valkenburgh, S. B., Crowley, W. F., Jr., Hayes, F. J.
|
|
<strong>The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2470-2475, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11397842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11397842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11397842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.6.7542" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Pitteloud2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr.
|
|
<strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Invest. 117: 457-463, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17235395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17235395</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17235395[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=17235395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI29884" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Pralong1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pralong, F. P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M. L., Portmann, L., Gaillard, R. C.
|
|
<strong>Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.</strong>
|
|
J. Clin. Endocr. Metab. 84: 3811-3816, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10523035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10523035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10523035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.10.6042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Sedlmeyer2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sedlmeyer, I. L., Pearce, C. L., Trueman, J. A., Butler, J. L., Bersaglieri, T., Read, A. P., Clayton, P. E., Kolonel, L. N., Henderson, B. E., Hirschhorn, J. N., Palmert, M. R.
|
|
<strong>Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing.</strong>
|
|
J. Clin. Endocr. Metab. 90: 1091-1099, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15546906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15546906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15546906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-0649" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Seminara2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E.
|
|
<strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong>
|
|
J. Clin. Endocr. Metab. 85: 556-562, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10690855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10690855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10690855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Silveira2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Silveira, L. F. G., Stewart, P. M., Thomas, M., Clark, D. A., Bouloux, P. M. G., MacColl, G. S.
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<strong>Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR 'knockout'.</strong>
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J. Clin. Endocr. Metab. 87: 2973-2977, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.87.6.8535" target="_blank">Full Text</a>]
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</p>
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</li>
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<a id="33" class="mim-anchor"></a>
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<a id="Soderlund2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Soderlund, D., Canto, P., de la Chesnaye, E., Ulloa-Aguirre, A., Mendez, J. P.
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<strong>A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene.</strong>
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Clin. Endocr. 54: 493-498, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11318785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11318785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11318785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1046/j.1365-2265.2001.01211.x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="34" class="mim-anchor"></a>
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<a id="Szende1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Szende, B., Srkalovic, G., Timar, J., Mulchahey, J. J., Neill, J. D., Lapis, K., Csikos, A., Szepeshazi, K., Schally, A. V.
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<strong>Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.</strong>
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Proc. Nat. Acad. Sci. 88: 4153-4156, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1851995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1851995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1851995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.88.10.4153" target="_blank">Full Text</a>]
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</p>
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 3/26/2015
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 9/27/2012<br>Ada Hamosh - updated : 8/27/2009<br>John A. Phillips, III - updated : 10/1/2007<br>Marla J. F. O'Neill - updated : 3/13/2007<br>John A. Phillips, III - updated : 10/20/2006<br>John A. Phillips, III - updated : 8/22/2006<br>John A. Phillips, III - updated : 8/6/2004<br>John A. Phillips, III - updated : 1/29/2004<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 10/2/2003<br>John A. Phillips, III - updated : 10/2/2003<br>John A. Phillips, III - updated : 1/23/2003<br>John A. Phillips, III - updated : 1/6/2003<br>John A. Phillips, III - updated : 10/31/2002<br>John A. Phillips, III - updated : 11/6/2001<br>John A. Phillips, III - updated : 8/13/2001<br>John A. Phillips, III - updated : 8/8/2001<br>John A. Phillips, III - updated : 3/16/2001<br>Victor A. McKusick - updated : 7/13/2000<br>John A. Phillips, III - updated : 4/3/2000<br>John A. Phillips, III - updated : 11/29/1999<br>John A. Phillips, III - updated : 10/14/1999<br>Victor A. McKusick - updated : 12/29/1997<br>Victor A. McKusick - updated : 12/5/1997<br>John A. Phillips, III - updated : 11/8/1997<br>Alan F. Scott - updated : 7/6/1995
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 2/1/1993
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/21/2022
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/18/2022<br>carol : 08/12/2016<br>carol : 03/28/2015<br>carol : 3/27/2015<br>mcolton : 3/26/2015<br>carol : 10/16/2012<br>carol : 10/11/2012<br>carol : 10/1/2012<br>carol : 9/27/2012<br>alopez : 9/3/2009<br>terry : 8/27/2009<br>carol : 6/24/2009<br>alopez : 10/1/2007<br>carol : 3/13/2007<br>carol : 2/22/2007<br>alopez : 10/20/2006<br>alopez : 8/22/2006<br>alopez : 8/6/2004<br>terry : 2/20/2004<br>alopez : 1/29/2004<br>alopez : 1/29/2004<br>cwells : 11/7/2003<br>tkritzer : 11/5/2003<br>terry : 11/3/2003<br>alopez : 10/2/2003<br>alopez : 10/2/2003<br>alopez : 1/23/2003<br>alopez : 1/6/2003<br>alopez : 10/31/2002<br>alopez : 11/6/2001<br>alopez : 8/13/2001<br>alopez : 8/8/2001<br>alopez : 8/8/2001<br>alopez : 3/16/2001<br>alopez : 7/21/2000<br>terry : 7/13/2000<br>alopez : 6/5/2000<br>terry : 4/3/2000<br>terry : 4/3/2000<br>alopez : 11/29/1999<br>alopez : 11/29/1999<br>alopez : 10/14/1999<br>alopez : 10/14/1999<br>alopez : 3/1/1999<br>dkim : 10/13/1998<br>terry : 1/7/1998<br>terry : 12/30/1997<br>terry : 12/29/1997<br>terry : 12/29/1997<br>alopez : 12/12/1997<br>mark : 12/5/1997<br>mark : 12/5/1997<br>alopez : 12/4/1997<br>alopez : 12/3/1997<br>mark : 10/20/1995<br>mark : 7/6/1995<br>terry : 1/27/1995<br>mimadm : 9/24/1994<br>carol : 5/13/1994<br>carol : 2/1/1993
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 138850
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<div>
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<h3>
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<span class="mim-font">
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GONADOTROPIN-RELEASING HORMONE RECEPTOR; GNRHR
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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GNRHR1<br />
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GRHR<br />
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LUTEINIZING HORMONE-RELEASING HORMONE RECEPTOR; LHRHR
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</span>
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<div>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GNRHR</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 4q13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 4:67,737,118-67,754,388 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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4q13.2
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</td>
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<td>
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<span class="mim-font">
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Hypogonadotropic hypogonadism 7 without anosmia
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</td>
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<td>
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<span class="mim-font">
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146110
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gonadotropin-releasing hormone (GNRH; 152760), a hypothalamic decapeptide, is a key neuroregulator of the reproductive process. It is synthesized by hypothalamic neurons, secreted in a pulsatile manner, and carried to the anterior lobe of the pituitary gland by way of the hypothalamohypophyseal portal circulation. The primary site of action of GNRH in the pituitary gland is the gonadotrope, the cell that expresses GNRH receptors and secretes gonadotropic hormones, which in turn regulate gametogenic and hormonal functions of the gonads. GNRH receptor is a member of the G protein-coupled, Ca(2+)-dependent family of receptors. Located on the cell surface of pituitary gonadotropes, GNRHR transduces signals from GNRH and modulates the synthesis and secretion of luteinizing hormone (152780) and follicle-stimulating hormone (136530).</p>
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</span>
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<div>
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<br />
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</div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kakar et al. (1992) isolated a cDNA for the GNRH receptor and showed that it encodes a protein with a transmembrane topology similar to that of other G protein-coupled 7-transmembrane-domain receptors. </p><p>Grosse et al. (1997) used RT-PCR of human pituitary poly(A)+ RNA to clone the full-length GNRHR gene and a second truncated cDNA characterized by a 128-bp deletion between nucleotide positions 522 and 651. The deletion causes a frameshift in the open reading frame, thus generating new coding sequence for a further 75 amino acids. The truncated cDNA arises from alternative splicing that uses a cryptic 3-prime splice site in exon 2. Translation products of approximately 45 to 50 and 42 kD were immunoprecipitated from COS-7 cells transfected with wildtype and truncated GNRHR cDNAs, respectively. The splice variant was incapable of ligand binding and signal transduction. Coexpression of wildtype and truncated proteins in transiently or stably transfected cells, resulted in impaired signaling via the wildtype GNRHR by reducing maximal agonist-induced inositol phosphate accumulation. This inhibitory effect depended on the amount of splice variant cDNA cotransfected and was specific for GNRHR. Coexpression of the wildtype and truncated GNRHRs resulted in impaired insertion of wildtype GNRHR into the plasma membrane. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using cDNA probes derived from a human pituitary cDNA library, Fan et al. (1994) screened a human genomic library and isolated 7 positive clones. The clones contained the entire protein coding region of the GNRHR gene, which is distributed among 3 exons and spans over 18.9 kb. The 2 introns, measuring 4.2 and 5.0 kb, were located within the open reading frame, indicating that the GNRHR gene is a member of the intron-containing class of the G protein-coupled receptor superfamily. Genomic Southern blot analysis demonstrated the presence of a single copy of the gene in the human genome. </p><p>Fan et al. (1995) showed that the GNRHR mRNA is approximately 5 kb long, of which 987 bp comprise the coding region. The gene appears to have large 5-prime and 3-prime untranslated regions, including, respectively, multiple transcription initiation sites and polyadenylation signals. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kaiser et al. (1994) used mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4 to localize the GNRHR gene to 4q13.1-q21.1. Furthermore, using linkage analysis of single-strand conformation polymorphisms, they localized the murine homolog to mouse chromosome 5. Using PCR analysis of DNA from human/hamster somatic hybrid cell lines, Fan et al. (1994) assigned the GNRHR gene to chromosome 4. By in situ hybridization using a biotinylated cDNA probe, Morrison et al. (1994) localized the GNRHR gene to 4q13.2-q13.3. By fluorescence in situ hybridization using a larger genomic clone as a probe, Leung et al. (1995) apparently achieved a more precise localization of the GNRHR gene to 4q21.2. </p><p>Kottler et al. (1995) isolated YAC clones containing the GNRHR gene. Genetic analysis of the YACs showed that the gene lies between D4S409 and D4S392, which are located 76 and 77 cM, respectively, from the end of the short arm of chromosome 4. Furthermore, by fluorescence in situ hybridization, Kottler et al. (1995) demonstrated colocalization of GNRHR with the KIT gene (164920), which has been mapped to 4q12. Kakar and Neill (1995) mapped the gene to 4q13 by PCR analysis of genomic DNA from human/hamster somatic cell hybrids combined with fluorescence in situ hybridization. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The growth of sex hormone-dependent tumors is inhibited by analogs of luteinizing hormone-releasing hormone (LHRH; 152760). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency. In addition, LHRH agonists and antagonists exert a direct effect on these tumors that probably is mediated by specific high-affinity LHRH receptors found on these cells. LHRH agonists and antagonists also suppress the growth of experimental pancreatic cancers. Szende et al. (1991) demonstrated that pancreatic tumor cells exhibit high-affinity binding sites for LHRH, but only in their nuclei; low-affinity sites are associated with the cell membranes. These binding sites appear to be LHRH receptors since electron microscopic immunohistochemical studies show that an antibody to the LHRH receptor reacted with sites in the nucleus of pancreatic tumor cells. </p><p>Maji et al. (2009) found that peptide and protein hormones, including GNRH, in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation, and concluded that functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a sister and brother with normosmic idiopathic hypogonadotropic hypogonadism (HH7; 146110), de Roux et al. (1997) identified compound heterozygosity for 2 missense mutations in the GNRHR gene (Q106R, 138850.0001 and R262Q, 138850.0002). </p><p>Layman et al. (1998) screened 46 unrelated patients with normosmic idiopathic HH for GNRHR mutations and identified compound heterozygosity for the R262Q mutation and another missense mutation (Y284C; 138850.0003) in 1 family with 4 affected sibs. </p><p>In 3 sibs from a kindred with isolated HH, Caron et al. (1999) identified compound heterozygosity for R262Q and another missense mutation in the GNRHR gene (A129D; 138850.0004). </p><p>Kottler et al. (1999) analyzed in detail the GNRHR mutations in 7 independent familial and sporadic cases of idiopathic hypogonadotropic hypogonadism reported to that time. The Q106R and R262Q mutations were frequent in patients from all geographic areas (North and South America and Europe). </p><p>In a brother and 2 sisters with HH, de Roux et al. (1999) identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene; in addition, all 3 sibs carried another GNRHR missense mutation (S217R; 138850.0005) on the same allele with Q106R. </p><p>In a male patient with complete HH, Pralong et al. (1999) identified homozygosity for a missense mutation in GNRHR (S168R; 138850.0006). </p><p>In a woman with complete HH, Kottler et al. (2000) identified compound heterozygosity for Q106R and a nonsense mutation in the GNRHR gene (L314X; 138850.0007). </p><p>In a 26-year-old male with a mild form of hypogonadotropic hypogonadism, Pitteloud et al. (2001) identified homozygosity for the R262Q mutation in the GNRHR gene. </p><p>Costa et al. (2001) investigated 17 Brazilian patients with normosmic HH and identified homozygosity for a GNRHR missense mutation (R139H; 138850.0008) in a female with complete HH and compound heterozygosity for Q106R and another GNRHR missense mutation (N10K; 138850.0009) in 3 sibs with partial HH. </p><p>To determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with idiopathic hypogonadotropic hypogonadism, Beranova et al. (2001) screened 108 probands with idiopathic hypogonadotropic hypogonadism for mutations in the coding sequence of GNRHR. Forty-eight of the 108 patients had a normal sense of smell, whereas the remaining 60 had anosmia or hyposmia (Kallmann syndrome). Five unrelated probands (3 men and 2 women), all normosmic, were documented to have changes in the coding sequence of the GNRHR. Two of these probands were from a subgroup of 5 kindreds consistent with a recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5 (40%) in patients with normosmic, autosomal recessive idiopathic hypogonadotropic hypogonadism. The remaining 3 probands with GNRHR mutations were from a subgroup of 18 patients without evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in patients with sporadic idiopathic hypogonadotropic hypogonadism and a normal sense of smell. Among the 5 individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted, including testicular sizes that varied from prepubertal to the normal adult male range. Three probands had compound heterozygous mutations, and 2 had homozygous mutations. Of the 8 DNA sequence changes identified, 4 were novel. COS-7 cells transiently transfected with cDNAs encoding the human GNRHR containing each of these 4 novel mutations failed to respond to GNRH agonist stimulation. </p><p>Janovick et al. (2002) showed pharmacologic rescue, assessed by ligand binding and restoration of receptor coupling to effector, of 5 naturally occurring GNRHR mutants identified from patients with hypogonadotropic hypogonadism, as well as rescue of other defective receptors manufactured with internal or terminal deletions or substitutions at sites expected to be involved in establishment of tertiary receptor structure. The pharmacologic agent used was a small, membrane-permeant molecule, originally designed as an orally active, nonpeptide receptor antagonist, but is believed to function as a folding template, capable of correcting the structural defects caused by the mutations and thereby restoring function. The rescued receptor, stabilized in the plasma membrane, coupled ligand binding to activation of the appropriate effector system. For comparison, low-, intermediate-, or high-affinity peptide antagonists of GNRHR (that do not penetrate the cell) were unable to effect rescue, as was a nonbinding peptidomimetic congener of the rescue agent; this latter effect demonstrates specificity of the rescue agent. Janovick et al. (2002) concluded that mutant GNRHRs frequently have not lost intrinsic functionality and are subject to rescue by techniques that enhance membrane expression. </p><p>Bedecarrats et al. (2003) analyzed 2 common mutations in GNRHR, gln106 to arg (Q106R; 138850.0001) and arg262 to gln (R262Q; 138850.0002), for their effects on the stimulation of gonadotropin subunit and GNRHR gene expression by GNRH. Despite similar impairment of GNRH-stimulated inositol phosphate production, dose-response analyses indicated that Q106R and R262Q both reduced the sensitivity of the FSH-beta (136530) gene promoter to a greater extent than LH-beta (152780) or the alpha-glycoprotein subunit (alpha-GSU; 118850), suggesting the involvement of more than one signaling pathway. Furthermore, although the sensitivities of the LH-beta and FSH-beta gene promoters to GNRH were similarly affected by both mutants, alpha-GSU sensitivity was decreased to a greater extent by R262Q than by Q106R. Similarly, GNRHR gene promoter sensitivity was significantly reduced only by R262Q. The authors concluded that differential stimulation of LH-beta, FSH-beta, and alpha-GSU gene expression may contribute to the varied phenotypes observed among patients harboring these mutations. </p><p>Leanos-Miranda et al. (2003) demonstrated that GNRHR mutants inhibited the function of wildtype GNRHR, measured by activation of effector and ligand binding. Inhibition varied depending on the particular GNRHR mutant coexpressed and the ratio of GNRHR mutant to wildtype GNRHR cDNA cotransfected. The GNRHR mutants did not interfere with the function of genetically modified GNRHRs bearing either a deletion of primate-specific lys191 or the carboxyl-terminal tail of catfish GNRHR. The dominant-negative effect of the naturally occurring receptor mutants occurred only for the wildtype GNRHR, which has intrinsic low maturation efficiency. The data suggested that this dominant-negative effect accompanies the diminished plasma membrane expression as a recent evolutionary event. </p><p>To determine whether genetic variation within either the GNRHR or GNRH1 genes contributes to the regulation of pubertal timing in the general population, Sedlmeyer et al. (2005) performed sequence analysis and haplotype-based association studies in individuals with later than average pubertal development. All observed associations were relatively modest and only nominally statistically significant. The authors concluded that genetic variation in GHRH1 and GNRHR is not likely to be a substantial modulator of pubertal timing in the general population. </p><p><strong><em>Oligogenic Inheritance</em></strong></p><p>
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In 2 sisters with primary amenorrhea and no breast development at 25 and 18 years of age, respectively (146110), Seminara et al. (2000) identified compound heterozygosity for Q106R on one allele and R262Q (138850.0002) on the other. The apparently unaffected parents were heterozygous for the mutations. Pitteloud et al. (2007) reexamined the family studied by Seminara et al. (2000) and identified heterozygosity for an additional missense mutation in the FGFR1 gene (136350.0016) in the 2 sisters and in their father, who had a history of delayed puberty. Mutation analysis of the children of the younger sister revealed that her unaffected daughter, who had undergone normal puberty, was heterozygous for the mutation in FGFR1 but had no mutations in the GNRHR gene, and that her prepubertal 10-year-old twin sons, born without cryptorchidism or microphallus, were each heterozygous for 1 of the mutations in GNRHR but did not have any mutations in the FGFR1 gene. Pitteloud et al. (2007) concluded that defects in 2 different genes can synergize to produce a more severe phenotype in families with hypogonadotropic hypogonadism than either alone, and that this digenic model may account for some of the phenotypic heterogeneity seen in GnRH deficiency. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>14 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, GLN106ARG
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<br />
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SNP: rs104893836,
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gnomAD: rs104893836,
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ClinVar: RCV000190591, RCV000255385, RCV000599632, RCV000662016, RCV001327939, RCV003330392, RCV003415714, RCV004018637
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a sister and brother with hypogonadotropic hypogonadism (HH7; 146110), de Roux et al. (1997) identified compound heterozygosity for a 317G-A transition in the GNRHR gene, resulting in a gln106-to-arg (Q106R) substitution, and a 785G-A transition, resulting in an arg262-to-gln (R262Q; 138850.0002) substitution. Both residues are highly conserved and are located in the first extracellular and third intracellular loop of the GNRH receptor, respectively. The unaffected parents and sister, who were clinically and endocrinologically normal, were each heterozygous for 1 of the mutations. Functional analysis demonstrated that GNRH binding was markedly reduced, but not eliminated, with the Q106R mutant, whereas GNRH binding was similar to wildtype with the R262Q mutant. </p><p>In a brother and 2 sisters with HH, de Roux et al. (1999) identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene; in addition, all 3 sibs carried another GNRHR missense mutation (S217R; 138850.0005) on the same allele with Q106R. </p><p>In 2 sisters with primary amenorrhea and no breast development at 25 and 18 years of age, respectively, Seminara et al. (2000) identified compound heterozygosity for the Q106R and R262Q mutations in the GNRHR gene. The apparently unaffected parents were heterozygous for the mutations. Pitteloud et al. (2007) reexamined this family and identified heterozygosity for an additional missense mutation in the FGFR1 gene (136350.0016) in the 2 sisters and in their father, who had a history of delayed puberty. Mutation analysis of the children of the younger sister revealed that her unaffected daughter, who underwent normal puberty, was heterozygous for the mutation in FGFR1 but had no mutations in the GNRHR gene, and that her prepubertal 10-year-old twin sons, born without cryptorchidism or microphallus, were each heterozygous for 1 of the mutations in the GNRHR gene but did not have any mutations in the FGFR1 gene. Pitteloud et al. (2007) concluded that defects in 2 different genes can synergize to produce a more severe phenotype in families with hypogonadotropic hypogonadism than either alone, and that this digenic model may account for some of the phenotypic heterogeneity seen in GnRH deficiency. </p><p>In a woman with complete HH, Kottler et al. (2000) identified compound heterozygosity for Q106R and a nonsense mutation in the GNRHR gene (L314X; 138850.0007). </p><p>In a 26-year-old male with mild HH, who had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and normal testicular size, and who developed sperm after treatment with CG (see 118860), Pitteloud et al. (2001) identified homozygosity for the Q106R mutation in the GNRHR gene. The authors noted that de Roux et al. (1997) had previously shown that GNRH binding is decreased, but not eliminated, with the Q106R mutant. </p><p>In 4 Brazilian sibs with partial HH, Costa et al. (2001) identified compound heterozygosity for Q106R and another missense mutation in the GNRHR gene (N10K; 138850.0009). </p><p>In 2 brothers with severe HH, Karges et al. (2003) identified compound heterozygosity for Q106R and another missense mutation in the GNRHR gene (A171T; 138850.0012). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, ARG262GLN
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<br />
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SNP: rs104893837,
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gnomAD: rs104893837,
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ClinVar: RCV000030908, RCV000494391, RCV001849268, RCV004584328, RCV004782017
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the arg262-to-gln (R262Q) mutation in the GNRHR gene that was found in compound heterozygous state in patients with hypogonadotropic hypogonadism (HH7; 146110) by de Roux et al. (1997) and Seminara et al. (2000), see 138850.0001. </p><p>The R262Q mutation in GNRHR was also found in compound heterozygous state in 4 sibs with HH by Layman et al. (1998) (see 138850.0003) and in 3 sibs with HH by Caron et al. (1999) (see 138850.0004). </p><p>De Roux et al. (1999) found the R262Q mutation in compound heterozygous state in 3 sibs with HH, who carried both the Q106R (138850.0001) and S217R (138850.0005) mutations on the other allele. </p><p>In 2 brothers with HH7, Lin et al. (2006) identified homozygosity for the R262Q mutation in the GNRHR gene. The proband, who presented at 15 years of age with delayed puberty, responded to a short course of testosterone with appropriate progress through puberty, whereas his younger brother showed little response after treatment. Lin et al. (2006) concluded that homozygous partial loss-of-function mutations in GNRHR, such as R262Q, can cause variable phenotypes, including apparent delayed puberty. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, TYR284CYS
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<br />
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SNP: rs28933074,
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gnomAD: rs28933074,
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ClinVar: RCV000030909
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 sibs with hypogonadotropic hypogonadism (HH7; 146110), Layman et al. (1998) identified compound heterozygosity for the R262Q mutation in the GNRHR gene (138850.0002) and an A-G transition resulting in a tyr284-to-cys (Y284C; 138850.0003) substitution in transmembrane region 6. The mutations were not found in an unaffected sib or in 75 unrelated controls. At least 1 of the affected females ovulated in response to exogenous gonadotropins. The 2 GNRHR mutations had minimal effects on receptor affinity, but receptor expression was decreased for both. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, ALA129ASP
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<br />
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SNP: rs104893838,
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gnomAD: rs104893838,
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ClinVar: RCV000030910, RCV001851889
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 sibs with isolated hypogonadotropic hypogonadism (HH7; 146110), Caron et al. (1999) identified compound heterozygosity for the R262Q mutation in the GNRHR gene (138850.0002) and a 386C-A transversion, resulting in an ala129-to-asp (A129D) substitution. Their unaffected parents were each heterozygous for 1 of the mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, SER217ARG
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<br />
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SNP: rs104893839,
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ClinVar: RCV000030911
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the ser217-to-arg (S217R) mutation in the GNRHR gene that was found in compound heterozygous state in 3 sibs with hypogonadotropic hypogonadism (HH7; 146110) by de Roux et al. (1999), see 138850.0001. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, SER168ARG
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<br />
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SNP: rs104893840,
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ClinVar: RCV000030912, RCV001849269
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Pralong et al. (1999) described a male patient with complete hypogonadotropic hypogonadism (HH7; 146110) who presented primary failure of pulsatile GNRH (152760) therapy, but responded to exogenous gonadotropin administration. The patient had a T-to-A transversion at codon 168 of the gene encoding the GNRH receptor (GNRHR), resulting in a ser168-to-arg (S168R) change in the fourth transmembrane domain of GNRHR. This mutation was present in homozygous state in the patient, whereas it was in heterozygous state in both phenotypically normal parents. When introduced into GNRHR cDNA, S168R resulted in complete loss of the receptor-mediated signaling response to GNRH. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, LEU314TER
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<br />
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SNP: rs104893841,
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ClinVar: RCV000030913
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a woman with complete hypogonadotropic hypogonadism (HH7; 146110), Kottler et al. (2000) identified compound heterozygosity for 2 mutations in the GNRHR gene: the Q106R mutation (138850.0001) and a leu314-to-ter (L314X) substitution, resulting in partial deletion of the seventh transmembrane domain. The L314X mutant receptor showed neither measurable binding nor inositol phosphate production when transfected in CHO-K1 cells compared to the wildtype receptor. Family members who were heterozygous for either mutation had normal pubertal development and fertility. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, ARG139HIS
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<br />
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SNP: rs104893842,
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gnomAD: rs104893842,
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ClinVar: RCV000030914, RCV000203470, RCV000497820
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Brazilian woman with complete hypogonadotropic hypogonadism (HH7; 146110), Costa et al. (2001) identified homozygosity for an arg139-to-his (R139H) substitution located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GNRHR gene. The R139H mutation completely eliminated detectable GNRH-binding activity and prevented GNRH-induced stimulation of inositol phosphate accumulation in vitro. The patient had undetectable serum basal LH and FSH levels that failed to respond to GNRH stimulation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, ASN10LYS
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<br />
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SNP: rs104893843,
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gnomAD: rs104893843,
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ClinVar: RCV000030915, RCV000375229
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 Brazilian sibs with partial hypogonadotropic hypogonadism (HH7; 146110), who had low serum basal LH levels that were responsive to GNRH stimulation, Costa et al. (2001) identified compound heterozygosity for the Q106R mutation in the GNRHR gene (138850.0001) and an asn10-to-lys (N10K; 138850.0009) substitution in the extracellular amino-terminal domain. The Q106R mutation had been shown by de Roux et al. (1997) to bind GNRH with reduced affinity, and in vitro analysis also demonstrated decreased affinity for GNRH with the N10K mutant compared to wildtype GNRHR. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, GLU90LYS
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<br />
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SNP: rs104893844,
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gnomAD: rs104893844,
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ClinVar: RCV000030916, RCV001560549
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs with the complete form of hypogonadotropic hypogonadism (HH7; 146110), Soderlund et al. (2001) detected a novel homozygous G-to-A transition at nucleotide 268 of the GNRHR gene, which resulted in a glu90-to-lys (E90K) amino acid substitution. This mutation is located in the second transmembrane domain of the GNRH receptor. To assess the functional role of E90, Maya-Nunez et al. (2002) performed mutation analysis of the E90K substitution. Transient expression of the mutant receptor in COS-7 cells resulted in a virtual abolition of GNRH agonist binding and agonist-stimulated phosphoinositide turnover, initially suggesting that E90 may be essential for GNRH binding. To examine the role of a site known to suppress GNRHR function, mutants with deletion of K191 from the GNRHR and/or addition of catfish Gnrhr intracellular C-terminal tail to GNRHR were prepared. Activation of intracellular signaling in response to buserelin was restored by deletion of K191 from the E90K mutant receptor but minimally by addition of the catfish GNRHR C-terminal tail. This study provided evidence that the E90K mutation impairs GNRHR-effector coupling. Maya-Nunez et al. (2002) concluded that the observation that sequence modifications that enhance surface expression of the receptor restore function presents the possibility that loss of surface expression may underlie the severe phenotype exhibited by hypogonadotropic hypogonadism patients bearing this mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0011 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNRHR, IVS1, G-A, -1
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<br />
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SNP: rs797044452,
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ClinVar: RCV000030917
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a woman with complete GNRH resistance (HH7; 146110), Silveira et al. (2002) identified homozygosity for a G-A transition at the intron 1/exon 2 boundary. RT-PCR analysis of RNA showed a transcript lacking all of exon 2, with splicing of exon 1 to exon 3 and creation of a frameshift, generating a coding sequence for 3 new amino acids followed by a stop codon. Although it was not clear whether the mutant receptor was actually expressed, the resultant mRNA sequence was presumed to produce a truncated receptor with no binding or signaling capacity. The proband presented with primary amenorrhea and absent thelarche and pubarche. Dynamic tests demonstrated absent spontaneous gonadotropin pulsatility, and there was no response to either exogenous pulsatile or acute GNRH administration. However, the patient responded to exogenous gonadotropin administration with a resulting normal pregnancy. Her unaffected sister was heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0012 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GNRHR, ALA171THR
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<br />
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SNP: rs74452732,
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gnomAD: rs74452732,
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ClinVar: RCV000030918
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 brothers with severe hypogonadotropic hypogonadism (HH7; 146110), Karges et al. (2003) identified compound heterozygosity for 2 mutations in the GNRHR gene: Q106R (138850.0001) and a 511G-A transition that results in an ala171-to-thr (A171T) substitution at transmembrane helix 4 (TMH4). After in vitro expression in human embryonic kidney 293T cells, the A171T mutant LHCGR exhibited a lack of phospholipase C activity in signal transduction. Specific receptor binding of radioisotope-labeled GNRH ligand was undetectable in transfected cells. Molecular modeling and dynamic simulation of the mutant receptor suggested the introduction of a stable hydrogen bond that impeded conformational mobility of the TMH3 and TMH4 domains required for sequential ligand binding and receptor activation, thus stabilizing the LHCGR in its inactive conformation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
|
|
GNRHR, ASN10LYS AND GLN11LYS
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<br />
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SNP: rs281865427,
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ClinVar: RCV000030915, RCV000030919, RCV000375229, RCV000498552
|
|
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Meysing et al. (2004) reported a normosmic woman with congenital idiopathic hypogonadotropic hypogonadism (HH7; 146110) in whom treatment with pulsatile GNRH resulted in an unusual response. The woman not only required an increased dose of pulsatile GNRH for ovarian follicular development, but LH secretion did not increase appropriately, estradiol levels remained low, and she did not ovulate spontaneously. Sequencing of the GNRHR coding sequence revealed compound heterozygosity for a 30T-A transversion in exon 1 of the GNRHR gene, resulting in a 2-amino acid substitution on one allele (N10K+Q11K), and a missense mutation on the other allele (P320L; 138850.0014). Introduction of the P320L mutation into the GNRH receptor led to failure of detectable ligand binding and failure of stimulation of inositol phosphate production and gonadotropin subunit gene promoter activity in response to GnRH in transiently transfected cells. Introduction of the N10K+Q11K mutation into the GNRH receptor resulted in reduced binding of a GNRH agonist to 25% of the wildtype receptor. In addition, the EC50 value for GNRH stimulation of inositol phosphate production was significantly increased, and the dose-response curves for stimulation of alpha-gonadotropin subunit (118850), LH-beta (152780), and FSH-beta (136530) gene transcription by GNRH were similarly shifted to the right. The authors proposed that these GNRHR mutations result in a rightward shift of the dose-response curves of gonadotropin responses to pulsatile GNRH in the subject and unmask the differential sensitivities of LH and FSH to GNRH, resulting in low LH and estradiol levels despite appropriate FSH secretion and follicular growth. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNRHR, PRO320LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893847,
|
|
|
|
|
|
|
|
ClinVar: RCV000030920
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro320-to-leu (P320L) mutation in the GNRHR gene that was found in compound heterozygous state in a woman with hypogonadotropic hypogonadism (HH7; 146110) by Meysing et al. (2004), see 138850.0013. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Mason et al. (1986)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
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<div>
|
|
<p />
|
|
</div>
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|
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<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Bedecarrats, G. Y., Linher, K. D., Kaiser, U. B.
|
|
<strong>Two common naturally occurring mutations in the human gonadotropin-releasing hormone (GnRH) receptor have differential effects on gonadotropin gene expression and on GnRH-mediated signal transduction.</strong>
|
|
J. Clin. Endocr. Metab. 88: 834-843, 2003.
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[PubMed: 12574221]
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[Full Text: https://doi.org/10.1210/jc.2002-020806]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Beranova, M., Oliveira, L. M. B., Bedecarrats, G. Y., Schipani, E., Vallejo, M., Ammini, A. C., Quintos, J. B., Hall, J. E., Martin, K. A., Hayes, F. J., Pitteloud, N., Kaiser, U. B., Crowley, W. F., Jr., Seminara, S. B.
|
|
<strong>Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 86: 1580-1588, 2001.
|
|
|
|
|
|
[PubMed: 11297587]
|
|
|
|
|
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[Full Text: https://doi.org/10.1210/jcem.86.4.7395]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Caron, P., Chauvin, S., Christin-Maitre, S., Bennet, A., Lahlou, N., Counis, R., Bouchard, P., Kottler, M.-L.
|
|
<strong>Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.</strong>
|
|
J. Clin. Endocr. Metab. 84: 990-996, 1999.
|
|
|
|
|
|
[PubMed: 10084584]
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|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.3.5518]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C.
|
|
<strong>Two novel mutations in the gonadotropin- releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2680-2686, 2001.
|
|
|
|
|
|
[PubMed: 11397871]
|
|
|
|
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[Full Text: https://doi.org/10.1210/jcem.86.6.7551]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G.
|
|
<strong>The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.</strong>
|
|
J. Clin. Endocr. Metab. 84: 567-572, 1999.
|
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|
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[PubMed: 10022417]
|
|
|
|
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[Full Text: https://doi.org/10.1210/jcem.84.2.5449]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E.
|
|
<strong>A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor.</strong>
|
|
New Eng. J. Med. 337: 1597-1602, 1997.
|
|
|
|
|
|
[PubMed: 9371856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199711273372205]
|
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Fan, N. C., Jeung, E.-B., Peng, C., Olofsson, J. I., Krisinger, J., Leung, P. C. K.
|
|
<strong>The human gonadotropin-releasing hormone (GnRH) receptor gene: cloning, genomic organization and chromosomal assignment.</strong>
|
|
Molec. Cell. Endocr. 103: R1-R6, 1994.
|
|
|
|
|
|
[PubMed: 7958384]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0303-7207(94)90087-6]
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</p>
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</li>
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Fan, N. C., Peng, C., Krisinger, J., Leung, P. C. K.
|
|
<strong>The human gonadotropin-releasing hormone receptor gene: complete structure including multiple promoters, transcription initiation sites, and polyadenylation signals.</strong>
|
|
Molec. Cell. Endocr. 107: R1-R8, 1995.
|
|
|
|
|
|
[PubMed: 7768323]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0303-7207(94)03460-b]
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</p>
|
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</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Grosse, R., Schoneberg, T., Schultz, G., Gudermann, T.
|
|
<strong>Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor.</strong>
|
|
Molec. Endocr. 11: 1305-1318, 1997.
|
|
|
|
|
|
[PubMed: 9259321]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/mend.11.9.9966]
|
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</p>
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janovick, J. A., Maya-Nunez, G., Conn, P. M.
|
|
<strong>Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target.</strong>
|
|
J. Clin. Endocr. Metab. 87: 3255-3262, 2002.
|
|
|
|
|
|
[PubMed: 12107234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.87.7.8582]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kaiser, U. B., Dushkin, H., Altherr, M. R., Beier, D. R., Chin, W. W.
|
|
<strong>Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5.</strong>
|
|
Genomics 20: 506-508, 1994.
|
|
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|
|
[PubMed: 8034328]
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[Full Text: https://doi.org/10.1006/geno.1994.1211]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kakar, S. S., Musgrove, L. C., Devor, D. C., Sellers, J. C., Neill, J. D.
|
|
<strong>Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 189: 289-295, 1992.
|
|
|
|
|
|
[PubMed: 1333190]
|
|
|
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|
|
[Full Text: https://doi.org/10.1016/0006-291x(92)91556-6]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kakar, S. S., Neill, J. D.
|
|
<strong>The human gonadotropin-releasing hormone receptor gene (GNRHR) maps to chromosome band 4q13.</strong>
|
|
Cytogenet. Cell Genet. 70: 211-214, 1995.
|
|
|
|
|
|
[PubMed: 7789173]
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[Full Text: https://doi.org/10.1159/000134035]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karges, B., Karges, W., Mine, M., Ludwig, L., Kuhne, R., Milgrom, E., de Roux, N.
|
|
<strong>Mutation ala(171)thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1873-1879, 2003.
|
|
|
|
|
|
[PubMed: 12679486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-020005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kottler, M. L., Lorenzo, F., Bergametti, F., Commercon, P., Souchier, C., Counis, R.
|
|
<strong>Subregional mapping of the human gonadotropin-releasing hormone receptor (GnRH-R) gene to 4q between the markers D4S392 and D4S409.</strong>
|
|
Hum. Genet. 96: 477-480, 1995.
|
|
|
|
|
|
[PubMed: 7557974]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00191810]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R.
|
|
<strong>A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.</strong>
|
|
J. Clin. Endocr. Metab. 85: 3002-3008, 2000.
|
|
|
|
|
|
[PubMed: 10999776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.9.6783]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kottler, M.-L., Counis, R., Bouchard, P.
|
|
<strong>Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.</strong>
|
|
Arch. Med. Res. 30: 481-485, 1999.
|
|
|
|
|
|
[PubMed: 10714361]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0188-4409(99)00072-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Layman, L. C., Cohen, D. P., Jin, M., Xie, J., Li, Z., Reindollar, R. H., Bolbolan, S., Bick, D. P., Sherins, R. R., Duck, L. W., Musgrove, L. C., Sellers, J. C., Neill, J. D.
|
|
<strong>Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. (Letter)</strong>
|
|
Nature Genet. 18: 14-15, 1998.
|
|
|
|
|
|
[PubMed: 9425890]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0198-14]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leanos-Miranda, A., Ulloa-Aguirre, A., Ji, T. H., Janovick, J. A., Conn, P. M.
|
|
<strong>Dominant-negative action of disease-causing gonadotropin-releasing hormone receptor (GnRHR) mutants: a trait that potentially coevolved with decreased plasma membrane expression of GnRHR in humans.</strong>
|
|
J. Clin. Endocr. Metab. 88: 3360-3367, 2003.
|
|
|
|
|
|
[PubMed: 12843188]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-030084]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leung, P. C. K., Squire, J., Peng, C., Fan, N., Hayden, M. R., Olofsson, J. I.
|
|
<strong>Mapping of the gonadotropin-releasing hormone (GnRH) receptor gene to human chromosome 4q21.2 by fluorescence in situ hybridization.</strong>
|
|
Mammalian Genome 6: 309-310, 1995.
|
|
|
|
|
|
[PubMed: 7613048]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00352431]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C.
|
|
<strong>A homozygous R262Q mutation in the gonadotropin-releasing hormone receptor presenting as constitutional delay of growth and puberty with subsequent borderline oligospermia.</strong>
|
|
J. Clin. Endocr. Metab. 91: 5117-5121, 2006.
|
|
|
|
|
|
[PubMed: 16968799]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2006-0807]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., Riek, R.
|
|
<strong>Functional amyloids as natural storage of peptide hormones in pituitary secretory granules.</strong>
|
|
Science 325: 328-332, 2009.
|
|
|
|
|
|
[PubMed: 19541956]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1173155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mason, A. J., Hayflick, J. S., Zoeller, R. T., Young, W. S., III, Phillips, H. S., Nikolics, K., Seeburg, P. H.
|
|
<strong>A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the 'hpg' mouse.</strong>
|
|
Science 234: 1366-1371, 1986.
|
|
|
|
|
|
[PubMed: 3024317]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3024317]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maya-Nunez, G., Janovick, J. A., Ulloa-Aguirre, A., Soderlund, D., Conn, P. M., Mendez, J. P.
|
|
<strong>Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E90K) GnRH receptor function by a deletion at a distant site.</strong>
|
|
J. Clin. Endocr. Metab. 87: 2144-2149, 2002.
|
|
|
|
|
|
[PubMed: 11994356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.87.5.8386]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meysing, A. U., Kanasaki, H., Bedecarrats, G. Y., Acierno, J. S., Jr., Conn, P. M., Martin, K. A., Seminara, S. B., Hall, J. E., Crowley, W. F., Jr., Kaiser, U. B.
|
|
<strong>GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone.</strong>
|
|
J. Clin. Endocr. Metab. 89: 3189-3198, 2004.
|
|
|
|
|
|
[PubMed: 15240592]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-031808]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morrison, N., Sellar, R. E., Boyd, E., Eidne, K. A., Connor, J. M.
|
|
<strong>Assignment of the gene encoding the human gonadotropin-releasing hormone receptor to 4q13.2-13.3 by fluorescence in situ hybridization.</strong>
|
|
Hum. Genet. 93: 714-715, 1994.
|
|
|
|
|
|
[PubMed: 8005601]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00201579]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pitteloud, N., Boepple, P. A., DeCruz, S., Valkenburgh, S. B., Crowley, W. F., Jr., Hayes, F. J.
|
|
<strong>The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.</strong>
|
|
J. Clin. Endocr. Metab. 86: 2470-2475, 2001.
|
|
|
|
|
|
[PubMed: 11397842]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.6.7542]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., Li, W.-P., Maccoll, G., Eliseenkova, A. V., Olsen, S. K., Ibrahimi, O. A., Hayes, F. J., Boepple, P., Hall, J. E., Bouloux, P., Mohammadi, M., Crowley, W., Jr.
|
|
<strong>Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Invest. 117: 457-463, 2007.
|
|
|
|
|
|
[PubMed: 17235395]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI29884]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pralong, F. P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M. L., Portmann, L., Gaillard, R. C.
|
|
<strong>Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.</strong>
|
|
J. Clin. Endocr. Metab. 84: 3811-3816, 1999.
|
|
|
|
|
|
[PubMed: 10523035]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.10.6042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sedlmeyer, I. L., Pearce, C. L., Trueman, J. A., Butler, J. L., Bersaglieri, T., Read, A. P., Clayton, P. E., Kolonel, L. N., Henderson, B. E., Hirschhorn, J. N., Palmert, M. R.
|
|
<strong>Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing.</strong>
|
|
J. Clin. Endocr. Metab. 90: 1091-1099, 2005.
|
|
|
|
|
|
[PubMed: 15546906]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-0649]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E.
|
|
<strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong>
|
|
J. Clin. Endocr. Metab. 85: 556-562, 2000.
|
|
|
|
|
|
[PubMed: 10690855]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.2.6357]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Silveira, L. F. G., Stewart, P. M., Thomas, M., Clark, D. A., Bouloux, P. M. G., MacColl, G. S.
|
|
<strong>Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR 'knockout'.</strong>
|
|
J. Clin. Endocr. Metab. 87: 2973-2977, 2002.
|
|
|
|
|
|
[PubMed: 12050282]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.87.6.8535]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soderlund, D., Canto, P., de la Chesnaye, E., Ulloa-Aguirre, A., Mendez, J. P.
|
|
<strong>A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene.</strong>
|
|
Clin. Endocr. 54: 493-498, 2001.
|
|
|
|
|
|
[PubMed: 11318785]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2265.2001.01211.x]
|
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|
|
|
</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
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Szende, B., Srkalovic, G., Timar, J., Mulchahey, J. J., Neill, J. D., Lapis, K., Csikos, A., Szepeshazi, K., Schally, A. V.
|
|
<strong>Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 4153-4156, 1991.
|
|
|
|
|
|
[PubMed: 1851995]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.10.4153]
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Marla J. F. O'Neill - updated : 3/26/2015<br>Marla J. F. O'Neill - updated : 9/27/2012<br>Ada Hamosh - updated : 8/27/2009<br>John A. Phillips, III - updated : 10/1/2007<br>Marla J. F. O'Neill - updated : 3/13/2007<br>John A. Phillips, III - updated : 10/20/2006<br>John A. Phillips, III - updated : 8/22/2006<br>John A. Phillips, III - updated : 8/6/2004<br>John A. Phillips, III - updated : 1/29/2004<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 10/2/2003<br>John A. Phillips, III - updated : 10/2/2003<br>John A. Phillips, III - updated : 1/23/2003<br>John A. Phillips, III - updated : 1/6/2003<br>John A. Phillips, III - updated : 10/31/2002<br>John A. Phillips, III - updated : 11/6/2001<br>John A. Phillips, III - updated : 8/13/2001<br>John A. Phillips, III - updated : 8/8/2001<br>John A. Phillips, III - updated : 3/16/2001<br>Victor A. McKusick - updated : 7/13/2000<br>John A. Phillips, III - updated : 4/3/2000<br>John A. Phillips, III - updated : 11/29/1999<br>John A. Phillips, III - updated : 10/14/1999<br>Victor A. McKusick - updated : 12/29/1997<br>Victor A. McKusick - updated : 12/5/1997<br>John A. Phillips, III - updated : 11/8/1997<br>Alan F. Scott - updated : 7/6/1995
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