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Entry
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- #146110 - HYPOGONADOTROPIC HYPOGONADISM 7 WITH OR WITHOUT ANOSMIA; HH7
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- OMIM
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<p>
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<span class="h4">#146110</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="/clinicalSynopsis/146110"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS147950"> <strong>Phenotypic Series</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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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#populationGenetics">Population Genetics</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" 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 class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=HYPOGONADOTROPIC HYPOGONADISM 7 WITH OR WITHOUT ANOSMIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=8668&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1334/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/3650" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=146110[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=432" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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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/disease/DOID:0090078" 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="http://www.informatics.jax.org/disease/146110" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0090078" 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': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></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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</div>
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 123953004<br />
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<strong>ORPHA:</strong> 432<br />
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<strong>DO:</strong> 0090078<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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146110
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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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HYPOGONADOTROPIC HYPOGONADISM 7 WITH OR WITHOUT ANOSMIA; HH7
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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HYPOGONADISM, ISOLATED HYPOGONADOTROPIC<br />
|
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IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; IHH
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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="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Phenotype-Gene 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 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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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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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>
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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">
|
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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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<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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<td>
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<span class="mim-font">
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GNRHR
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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/138850"> 138850 </a>
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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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<a href="/clinicalSynopsis/146110" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS147950" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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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">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/146110" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/146110" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Nose </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Normal sense of smell <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299900007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299900007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576648&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576648</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> CHEST </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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|
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<div>
|
|
<span class="mim-font">
|
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|
|
- Delayed or absent thelarche <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553927&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553927</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025515</a>]</span><br /> -
|
|
Gynecomastia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4754008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4754008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N62</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000771</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000771</a>]</span><br />
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|
|
|
</span>
|
|
</div>
|
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|
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</div>
|
|
|
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</div>
|
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> External Genitalia (Male) </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Small penis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/34911001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">34911001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276333003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276333003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q55.62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q55.62</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.64" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.64</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240701&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240701</a>, <a href="https://bioportal.bioontology.org/search?q=C4551492&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551492</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030260</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000054" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000054</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000054" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000054</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Internal Genitalia (Male) </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Small testes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276411001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276411001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241355</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008734" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008734</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008734" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008734</a>]</span><br /> -
|
|
Cryptorchidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204878001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010417</a>, <a href="https://bioportal.bioontology.org/search?q=C5441920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span><br /> -
|
|
Infertility (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8619003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8619003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15296000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15296000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4074771&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4074771</a>, <a href="https://bioportal.bioontology.org/search?q=C0021359&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021359</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Internal Genitalia (Female) </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Infertility (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8619003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8619003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15296000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15296000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4074771&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4074771</a>, <a href="https://bioportal.bioontology.org/search?q=C0021359&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021359</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span><br /> -
|
|
Primary amenorrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/156035004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">156035004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8913004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8913004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N91.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N91.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232939&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232939</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000786" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000786</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000786" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000786</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
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</div>
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|
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</div>
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
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|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Hair </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sparse to absent male facial hair <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231485</a>]</span><br /> -
|
|
Sparse to absent axillary hair <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858574&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858574</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002215" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002215</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002215" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002215</a>]</span><br /> -
|
|
Sparse to absent pubic hair <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858573&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858573</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002225" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002225</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002225" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002225</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> VOICE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Puerile voice <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231484</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Isolated hypogonadotropic hypogonadism <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3489396&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3489396</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22053006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22053006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33927004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405769009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405769009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E23.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E23.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/758.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">758.7</a>]</span><br /> -
|
|
Delayed or absent puberty <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2677536&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2677536</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000823" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000823</a>]</span><br /> -
|
|
Infertility (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8619003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8619003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15296000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15296000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4074771&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4074771</a>, <a href="https://bioportal.bioontology.org/search?q=C0021359&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021359</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000789</a>]</span><br /> -
|
|
Low luteinizing hormone (LH, see <a href="/entry/152780">152780</a>) levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4015262&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4015262</a>]</span><br /> -
|
|
Low follicle-stimulating hormone (FSH, see <a href="/entry/136530">136530</a>) levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4015263&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4015263</a>]</span><br /> -
|
|
Low testosterone levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011625&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011625</a>]</span><br /> -
|
|
Low estradiol levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011626&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011626</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Phenotypic variability has been described, with some patients exhibiting partial and others complete hypogonadotropic hypogonadism<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the gonadotropin-releasing hormone receptor gene (GNRHR, <a href="/entry/138850#0001">138850.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Hypogonadotropic hypogonadism with or without anosmia
|
|
- <a href="/phenotypicSeries/PS147950">PS147950</a>
|
|
- 27 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/952?start=-3&limit=10&highlight=952"> 1p13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619755"> ?Hypogonadotropic hypogonadism 27 without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619755"> 619755 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162361"> NHLH2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162361"> 162361 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1607?start=-3&limit=10&highlight=1607"> 1q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614842"> ?Hypogonadotropic hypogonadism 13 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614842"> 614842 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603286"> KISS1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603286"> 603286 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/631?start=-3&limit=10&highlight=631"> 2q14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614880"> {Hypogonadotropic hypogonadism 15 with or without anosmia} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614880"> 614880 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604846"> HS6ST1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604846"> 604846 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/410?start=-3&limit=10&highlight=410"> 3p14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615267"> Hypogonadotropic hypogonadism 18 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615267"> 615267 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606807"> IL17RD </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606807"> 606807 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/459?start=-3&limit=10&highlight=459"> 3p13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610628"> Hypogonadotropic hypogonadism 4 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610628"> 610628 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607002"> PROK2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607002"> 607002 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/255?start=-3&limit=10&highlight=255"> 4q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146110"> Hypogonadotropic hypogonadism 7 without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146110"> 146110 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138850"> GNRHR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138850"> 138850 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
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|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/456?start=-3&limit=10&highlight=456"> 4q24 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614840"> Hypogonadotropic hypogonadism 11 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614840"> 614840 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162332"> TACR3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162332"> 162332 </a>
|
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</span>
|
|
</td>
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</tr>
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|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/524?start=-3&limit=10&highlight=524"> 4q27 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618841"> Hypogonadotropic hypogonadism 25 with anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618841"> 618841 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616506"> NDNF </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616506"> 616506 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/616?start=-3&limit=10&highlight=616"> 5q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615266"> Hypogonadotropic hypogonadism 17 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615266"> 615266 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607984"> SPRY4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607984"> 607984 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/380?start=-3&limit=10&highlight=380"> 7q21.11 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614897"> {Hypogonadotropic hypogonadism 16 with or without anosmia} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614897"> 614897 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603961"> SEMA3A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603961"> 603961 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/622?start=-3&limit=10&highlight=622"> 7q31.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616030"> Hypogonadotropic hypogonadism 22, with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616030"> 616030 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613301"> FEZF1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613301"> 613301 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/99?start=-3&limit=10&highlight=99"> 8p21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615270"> Hypogonadotropic hypogonadism 20 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615270"> 615270 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603725"> FGF17 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603725"> 603725 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/139?start=-3&limit=10&highlight=139"> 8p21.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614841"> ?Hypogonadotropic hypogonadism 12 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614841"> 614841 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/152760"> GNRH1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/152760"> 152760 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/211?start=-3&limit=10&highlight=211"> 8p11.23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/147950"> Hypogonadotropic hypogonadism 2 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/147950"> 147950 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/136350"> FGFR1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/136350"> 136350 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/295?start=-3&limit=10&highlight=295"> 8q12.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612370"> Hypogonadotropic hypogonadism 5 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612370"> 612370 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608892"> CHD7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608892"> 608892 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/698?start=-3&limit=10&highlight=698"> 9q34.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614838"> Hypogonadotropic hypogonadism 9 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614838"> 614838 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608137"> NSMF </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608137"> 608137 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/502?start=-3&limit=10&highlight=502"> 10q24.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612702"> Hypogonadotropic hypogonadism 6 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612702"> 612702 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600483"> FGF8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600483"> 600483 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/617?start=-3&limit=10&highlight=617"> 10q26.12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614858"> Hypogonadotropic hypogonadism 14 with or without anosmia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614858"> 614858 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606417"> WDR11 </a>
|
|
</span>
|
|
</td>
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<span class="mim-font">
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<a href="/entry/229070"> Hypogonadotropic hypogonadism 24 without anosmia </a>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/229070"> 229070 </a>
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<a href="/entry/136530"> FSHB </a>
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<span class="mim-font">
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<a href="/entry/136530"> 136530 </a>
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<a href="/geneMap/12/528?start=-3&limit=10&highlight=528"> 12q13.3 </a>
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<span class="mim-font">
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<a href="/entry/614839"> Hypogonadotropic hypogonadism 10 with or without anosmia </a>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/614839"> 614839 </a>
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<span class="mim-font">
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<a href="/entry/162330"> TAC3 </a>
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<span class="mim-font">
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<a href="/entry/162330"> 162330 </a>
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<a href="/geneMap/12/669?start=-3&limit=10&highlight=669"> 12q21.33 </a>
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<span class="mim-font">
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<a href="/entry/615269"> Hypogonadotropic hypogonadism 19 with or without anosmia </a>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/615269"> 615269 </a>
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<span class="mim-font">
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<a href="/entry/602748"> DUSP6 </a>
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<span class="mim-font">
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<a href="/entry/602748"> 602748 </a>
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<a href="/geneMap/15/242?start=-3&limit=10&highlight=242"> 15q21.3 </a>
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<span class="mim-font">
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<a href="/entry/619718"> Hypogonadotropic hypogonadism 26 with or without anosmia </a>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/619718"> 619718 </a>
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<span class="mim-font">
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<a href="/entry/600480"> TCF12 </a>
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<span class="mim-font">
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<a href="/entry/600480"> 600480 </a>
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<span class="mim-font">
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<a href="/geneMap/19/35?start=-3&limit=10&highlight=35"> 19p13.3 </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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<a href="/entry/614837"> Hypogonadotropic hypogonadism 8 with or without anosmia </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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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<td>
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<span class="mim-font">
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<a href="/entry/614837"> 614837 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/604161"> KISS1R </a>
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</span>
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<span class="mim-font">
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<a href="/entry/604161"> 604161 </a>
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</span>
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<span class="mim-font">
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<a href="/geneMap/19/923?start=-3&limit=10&highlight=923"> 19q13.33 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/228300"> Hypogonadotropic hypogonadism 23 with or without anosmia </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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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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<span class="mim-font">
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<a href="/entry/228300"> 228300 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/152780"> LHB </a>
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<span class="mim-font">
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<a href="/entry/152780"> 152780 </a>
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<a href="/geneMap/20/80?start=-3&limit=10&highlight=80"> 20p12.3 </a>
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</span>
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</td>
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<span class="mim-font">
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<a href="/entry/244200"> Hypogonadotropic hypogonadism 3 with or without anosmia </a>
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</span>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/244200"> 244200 </a>
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<span class="mim-font">
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<a href="/entry/607123"> PROKR2 </a>
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<span class="mim-font">
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<a href="/entry/607123"> 607123 </a>
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<a href="/geneMap/20/108?start=-3&limit=10&highlight=108"> 20p12.1 </a>
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<span class="mim-font">
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<a href="/entry/615271"> Hypogonadotropic hypogonadism 21 with anosmia </a>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/615271"> 615271 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/604808"> FLRT3 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/604808"> 604808 </a>
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<span class="mim-font">
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<a href="/geneMap/X/43?start=-3&limit=10&highlight=43"> Xp22.31 </a>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/308700"> Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/308700"> 308700 </a>
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<a href="/entry/300836"> ANOS1 </a>
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<span class="mim-font">
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<a href="/entry/300836"> 300836 </a>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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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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<p>A number sign (#) is used with this entry because hypogonadotropic hypogonadism-7 with or without anosmia (HH7) is caused by homozygous or compound heterozygous mutation in the GNRHR gene (<a href="/entry/138850">138850</a>) on chromosome 4q13, sometimes in association with mutation in another gene, e.g., FGFR1 (<a href="/entry/136350">136350</a>).</p>
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<a id="description" class="mim-anchor"></a>
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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<p>Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; <a href="/entry/152760">152760</a>) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by <a href="#17" class="mim-tip-reference" title="Raivio, T., Falardeau, J., Dwyer, A., Quinton, R., Hayes, F. J., Hughes, V. A., Cole, L. W., Pearce, S. H., Lee, H., Boepple, P., Crowley, W. F., Jr., Pitteloud, N. <strong>Reversal of idiopathic hypogonadotropic hypogonadism.</strong> New Eng. J. Med. 357: 863-873, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17761590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17761590</a>] [<a href="https://doi.org/10.1056/NEJMoa066494" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17761590">Raivio et al., 2007</a>). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17761590" 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>For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see <a href="/entry/147950">147950</a>.</p>
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<strong>Clinical Features</strong>
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<p><a href="#7" 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> studied a brother and sister with normosmic hypogonadotropic hypogonadism. The 22-year-old propositus was referred because of hypogonadism and impaired libido, who had undergone puberty at age 16. His height was 180 cm and his arm span 186 cm. Physical examination revealed absence of facial hair, sparse pubic hair (Tanner stage 3), and a penis of 6 cm. He had scrotal testes, and the volume of each was 8 ml (normal, 15 to 25 ml). There was no gynecomastia. He had a normal sense of smell and no mirror movements of the upper limbs, no abnormal eye movements, no colorblindness, and no renal or craniofacial abnormalities. The karyotype was 46,XY. The patient's 37-year-old sister had a history of primary amenorrhea and infertility. Spontaneous thelarche had occurred at age 14 years. She had a single episode of uterine bleeding at age 18, and afterward received combined oral contraceptive treatment. This treatment was interrupted when she desired children. However, amenorrhea and absence of pregnancy led to ovulation-inducing treatment, which resulted in 2 normal pregnancies and the births of a girl and a boy, 4 and 7 years old at the time of report. After each pregnancy, she had persistent amenorrhea, and oral contraceptive treatment was resumed. Her height was 165 cm. Pubic hair development was at Tanner stage 5, and her breasts and external genitalia were those of a normal woman. Both parents and a sister were clinically and endocrinologically normal. <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="#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> studied 3 sibs with mutations in GNRHR from a kindred with isolated hypogonadotropic hypogonadism. The 2 brothers, who were referred for lack of puberty, had microphallus and bilateral cryptorchidism; their sister had primary amenorrhea and a complete lack of puberty. The authors concluded that these hypogonadal patients were partially resistant to pulsatile GNRH administration, suggesting that they should instead be treated with gonadotropins to induce spermatogenesis or ovulation. <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="#14" 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> reported a 26-year-old male with a mild form of hypogonadotropic hypogonadism, which they called a 'fertile eunuch variant' of HH. The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with chorionic gonadotropin (CG; see <a href="/entry/118860">118860</a>) alone, he developed sperm in his ejaculate, and his wife conceived. Following cessation of CG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone (LH; see <a href="/entry/152780">152780</a>) secretion. The authors concluded that this case expanded the clinical spectrum of GNRHR mutations, providing the first genetic basis for the fertile eunuch variant of hypogonadotropic hypogonadism and documenting the occurrence of reversible hypogonadotropic hypogonadism in a patient with a GNRHR mutation. <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><strong><em>Clinical Variability</em></strong></p><p>
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<a href="#6" 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> performed detailed endocrinologic studies in 3 affected members of a family with hypogonadotropic hypogonadism who had mutations in GNRHR (see MOLECULAR GENETICS). The proband, a 30-year-old male, had complete HH with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha subunit (see <a href="/entry/152780">152780</a>), absence of response to GNRH (<a href="/entry/152760">152760</a>) and GNRH agonist (triptorelin), and absence of effect of pulsatile administration of GNRH. His affected 18- and 24-year-old sisters had only partial hypogonadotropic hypogonadism. They both had primary amenorrhea and normal breast development, but the younger sister had retarded bone maturation and uterus development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GNRH. In both sisters, there were no spontaneous pulses of LH, but pulsatile administration of GNRH provoked pulsatile secretion of LH in the younger one. The authors concluded that the same GNRHR mutations may exhibit varying degrees of alteration of gonadotropin function in affected members of the same family. <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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<p><a href="#8" 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. <a href="#8" 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, and that the findings demonstrated the efficacy of an approach based on pharmacologic rescue and suggested the basis of new approaches for intervention in this and similar disorders. <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>
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<p>The transmission pattern of hypogonadotropic hypogonadism in the family reported by <a href="#7" 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> was consistent with autosomal recessive inheritance. <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>
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<p>In a brother and sister with normosmic hypogonadotropic hypogonadism, <a href="#7" 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="/entry/138850#0001">138850.0001</a> and R262Q, <a href="/entry/138850#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="#11" 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, including 32 males at least 18 years of age and 14 females at least 17 years of age, and identified compound heterozygosity for the R262Q mutation and another missense mutation (Y284C; <a href="/entry/138850#0003">138850.0003</a>) in 1 family with 4 affected sibs. At least 1 of the affected females ovulated in response to exogenous gonadotropins. <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 the R262Q mutation and another missense mutation in GNRHR (A129D; <a href="/entry/138850#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="#10" 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="#6" 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 3 missense mutations in the GNRHR gene, with R262Q on 1 allele, and Q106R and S217R (<a href="/entry/138850#0005">138850.0005</a>) on the other allele. Endocrinologic analysis demonstrated varying degrees of alteration of gonadotropin function in the 3 sibs, although they all carried the same mutations. <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, who presented with primary failure of pulsatile GNRH (<a href="/entry/152760">152760</a>) therapy but responded to exogenous gonadotropin administration, <a href="#16" 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 the GNRHR gene (S168R; <a href="/entry/138850#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="#9" 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 (L314X; <a href="/entry/138850#0007">138850.0007</a>) in the GNRHR gene. <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="#14" 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="#5" 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, 10 males and 7 females, from 14 different families with normosmic hypogonadotropic hypogonadism. The diagnosis of HH was based on absent or incomplete sexual development after 17 years of age associated with low or normal levels of LH in both sexes and low levels of testosterone in males and of estradiol in females. All patients presented with a normal sense of smell in an olfactory-specific test. In 1 female patient with complete HH, who had undetectable serum basal LH and FSH levels that failed to respond to GNRH stimulation, <a href="#5" 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 a missense mutation in the GNRHR gene (R139H; <a href="/entry/138850#0008">138850.0008</a>). In 4 sibs with partial HH, who had low serum basal LH levels that were responsive to GNRH stimulation, they identified compound heterozygosity for the Q106R mutation and another missense mutation in GNRHR (N10K; <a href="/entry/138850#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 a woman with primary amenorrhea and absent thelarche and pubarche, <a href="#19" 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 splice site mutation (<a href="/entry/138850#0011">138850.0011</a>). The patient had no spontaneous gonadotropin pulsatility and did not respond to either exogenous pulsatile or acute GNRH administration, but exogenous gonadotropin administration resulted in a normal pregnancy. <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><p><a href="#13" 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 female patient with congenital idiopathic HH in whom treatment with pulsatile GNRH resulted in an unusual response: she 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. Analysis of the GNRHR coding sequence revealed compound heterozygous GNRHR mutations (<a href="/entry/138850#0013">138850.0013</a> and <a href="/entry/138850#0014">138850.0014</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><p>In 2 brothers with HH, <a href="#12" 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> reported homozygosity for the R262Q mutation in GNRHR. The proband presented at 15 years of age with delayed puberty. After a short course of testosterone, he seemed to be progressing through puberty appropriately and was discharged from follow-up. His younger brother was also referred with delayed puberty but showed little progress after treatment. <a href="#12" 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 present with 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><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="#18" 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="#15" 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="#18" 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="#15" 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><strong><em>Possible Association with Functional Hypothalamic Amenorrhea in Carrier Females</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., Avbelj, M., Dhruvakumar, S., Plummer, L., Hughes, V. A., Seminara, S. B., Boepple, P. A., Sidis, Y., Crowley, W. F., Jr., Martin, K. A., Hall, J. E., Pitteloud, N. <strong>A genetic basis for functional hypothalamic amenorrhea.</strong> New Eng. J. Med. 364: 215-225, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21247312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21247312</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21247312[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/10.1056/NEJMoa0911064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21247312">Caronia et al. (2011)</a> studied 55 women with functional hypothalamic amenorrhea, who had all completed puberty spontaneously and had a history of secondary amenorrhea for 6 months or more, with low or normal gonadotropin levels and low serum estradiol levels. All had 1 or more predisposing factors, including excessive exercise, loss of more than 15% of body weight, and/or a subclinical eating disorder, and all had normal results on neuroimaging. The authors screened 7 HH-associated genes in the 55 affected women and identified 7 patients from 6 families who carried heterozygous mutations, including 1 in KAL1, 2 in FGFR1, 2 in PROKR2 (<a href="/entry/607123">607123</a>), and 1 in the GNRHR gene. Since these women with mutations resumed regular menses after discontinuing hormone-replacement therapy, <a href="#4" class="mim-tip-reference" title="Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., Avbelj, M., Dhruvakumar, S., Plummer, L., Hughes, V. A., Seminara, S. B., Boepple, P. A., Sidis, Y., Crowley, W. F., Jr., Martin, K. A., Hall, J. E., Pitteloud, N. <strong>A genetic basis for functional hypothalamic amenorrhea.</strong> New Eng. J. Med. 364: 215-225, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21247312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21247312</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21247312[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/10.1056/NEJMoa0911064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21247312">Caronia et al. (2011)</a> concluded that the genetic component of hypothalamic amenorrhea predisposes patients to, but is not sufficient to cause, GnRH deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21247312" 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>To determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with idiopathic hypogonadotropic hypogonadism, <a href="#1" 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 gene. 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. <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="#2" class="mim-tip-reference" title="Bhagavath, B., Ozata, M., Ozdemir, I. C., Bolu, E., Bick, D. P., Sherins, R. J., Layman, L. C. <strong>The prevalence of gonadotropin-releasing hormone receptor mutations in a large cohort of patients with hypogonadotropic hypogonadism.</strong> Fertil. Steril. 84: 951-957, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16213849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16213849</a>] [<a href="https://doi.org/10.1016/j.fertnstert.2005.04.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16213849">Bhagavath et al. (2005)</a> analyzed DNA from 185 HH patients and identified compound heterozygous GNRHR mutations in 3 (1.6%). All 3 were Caucasian, from a cohort of 85 HH patients with documented normosmia, and both the male patients as well as the female patient had so-called 'complete' HH, in which there is no evidence of steroid production as evidenced by a completely prepubertal phenotype. No mutations were found in the hyposmic or anosmic HH patients. GNRHR mutations were identified in 1 (6.7%) of 15 families with at least 2 affected sibs and in 2 (11.1%) of 18 normosmic HH females. No mutations were found in presumed autosomal dominant families. <a href="#2" class="mim-tip-reference" title="Bhagavath, B., Ozata, M., Ozdemir, I. C., Bolu, E., Bick, D. P., Sherins, R. J., Layman, L. C. <strong>The prevalence of gonadotropin-releasing hormone receptor mutations in a large cohort of patients with hypogonadotropic hypogonadism.</strong> Fertil. Steril. 84: 951-957, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16213849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16213849</a>] [<a href="https://doi.org/10.1016/j.fertnstert.2005.04.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16213849">Bhagavath et al. (2005)</a> concluded that GNRHR mutations account for approximately 3.5% of all normosmic HH and 7 to 11% of presumed autosomal recessive HH, suggesting that additional genes play an important role in normal puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16213849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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</div>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Beranova2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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: <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>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.4.7395" target="_blank">Full Text</a>]
|
|
|
|
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</p>
|
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|
|
</li>
|
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|
|
<li>
|
|
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|
|
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|
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|
|
Bhagavath, B., Ozata, M., Ozdemir, I. C., Bolu, E., Bick, D. P., Sherins, R. J., Layman, L. C.
|
|
<strong>The prevalence of gonadotropin-releasing hormone receptor mutations in a large cohort of patients with hypogonadotropic hypogonadism.</strong>
|
|
Fertil. Steril. 84: 951-957, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16213849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16213849</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16213849" 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/10.1016/j.fertnstert.2005.04.029" target="_blank">Full Text</a>]
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Caron1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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: <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>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.3.5518" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Caronia2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., Avbelj, M., Dhruvakumar, S., Plummer, L., Hughes, V. A., Seminara, S. B., Boepple, P. A., Sidis, Y., Crowley, W. F., Jr., Martin, K. A., Hall, J. E., Pitteloud, N.
|
|
<strong>A genetic basis for functional hypothalamic amenorrhea.</strong>
|
|
New Eng. J. Med. 364: 215-225, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21247312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21247312</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21247312[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=21247312" 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/NEJMoa0911064" target="_blank">Full Text</a>]
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Costa2001" class="mim-anchor"></a>
|
|
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|
|
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|
|
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>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="de Roux1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.2.5449" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="de Roux1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<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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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" 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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|
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[<a href="https://doi.org/10.1210/jcem.87.7.8582" target="_blank">Full Text</a>]
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
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<a id="Kottler2000" class="mim-anchor"></a>
|
|
<div class="">
|
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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>]
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|
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[<a href="https://doi.org/10.1210/jcem.85.9.6783" target="_blank">Full Text</a>]
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|
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|
|
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|
|
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|
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<a id="Kottler1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
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>]
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[<a href="https://doi.org/10.1016/s0188-4409(99)00072-7" target="_blank">Full Text</a>]
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<a id="Layman1998" class="mim-anchor"></a>
|
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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>]
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[<a href="https://doi.org/10.1038/ng0198-14" target="_blank">Full Text</a>]
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<a id="Lin2006" class="mim-anchor"></a>
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Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C.
|
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<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.
|
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|
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|
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[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>]
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[<a href="https://doi.org/10.1210/jc.2006-0807" target="_blank">Full Text</a>]
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|
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|
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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>]
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[<a href="https://doi.org/10.1210/jc.2003-031808" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Pitteloud2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
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[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>]
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[<a href="https://doi.org/10.1210/jcem.86.6.7542" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Pitteloud2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
|
|
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|
|
[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>]
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[<a href="https://doi.org/10.1172/JCI29884" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Pralong1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
|
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|
|
[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>]
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[<a href="https://doi.org/10.1210/jcem.84.10.6042" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Raivio2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Raivio, T., Falardeau, J., Dwyer, A., Quinton, R., Hayes, F. J., Hughes, V. A., Cole, L. W., Pearce, S. H., Lee, H., Boepple, P., Crowley, W. F., Jr., Pitteloud, N.
|
|
<strong>Reversal of idiopathic hypogonadotropic hypogonadism.</strong>
|
|
New Eng. J. Med. 357: 863-873, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17761590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17761590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17761590" 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/NEJMoa066494" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Seminara2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
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[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>]
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[<a href="https://doi.org/10.1210/jcem.85.2.6357" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<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>
|
|
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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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 04/06/2017
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 2/9/2016<br>Marla J. F. O'Neill - updated : 3/25/2015<br>Marla J. F. O'Neill - updated : 10/19/2012<br>Marla J. F. O'Neill - updated : 10/11/2012<br>Marla J. F. O'Neill - updated : 9/27/2012<br>Marla J. F. O'Neill - updated : 2/23/2012<br>Marla J. F. O'Neill - updated : 7/14/2009<br>Marla J. F. O'Neill - updated : 4/30/2009<br>Marla J. F. O'Neill - updated : 3/23/2009<br>Marla J. F. O'Neill - updated : 10/31/2008<br>Marla J. F. O'Neill - updated : 10/8/2008<br>Marla J. F. O'Neill - updated : 3/13/2007<br>John A. Phillips, III - updated : 8/21/2006<br>Marla J. F. O'Neill - updated : 6/2/2006<br>John A. Phillips, III - updated : 1/29/2004<br>John A. Phillips, III - updated : 1/29/2004<br>Victor A. McKusick - updated : 12/8/2003<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 1/6/2003<br>John A. Phillips, III - updated : 7/25/2002<br>John A. Phillips, III - updated : 2/23/2000<br>John A. Phillips, III - updated : 7/16/1998<br>John A. Phillips, III - updated : 12/20/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 7/6/1990
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/26/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/06/2017<br>carol : 08/05/2016<br>carol : 05/24/2016<br>carol : 2/9/2016<br>carol : 3/27/2015<br>mcolton : 3/25/2015<br>carol : 10/19/2012<br>carol : 10/11/2012<br>terry : 10/4/2012<br>carol : 9/27/2012<br>carol : 9/27/2012<br>carol : 4/18/2012<br>terry : 3/19/2012<br>carol : 2/23/2012<br>terry : 2/23/2012<br>carol : 11/10/2009<br>carol : 7/14/2009<br>terry : 7/14/2009<br>terry : 6/4/2009<br>wwang : 5/5/2009<br>terry : 4/30/2009<br>wwang : 3/30/2009<br>terry : 3/23/2009<br>joanna : 3/9/2009<br>wwang : 11/6/2008<br>terry : 10/31/2008<br>wwang : 10/15/2008<br>terry : 10/8/2008<br>terry : 9/25/2008<br>carol : 4/16/2007<br>carol : 3/14/2007<br>carol : 3/13/2007<br>alopez : 8/21/2006<br>carol : 6/2/2006<br>carol : 6/2/2006<br>terry : 6/2/2006<br>tkritzer : 7/14/2004<br>carol : 2/23/2004<br>alopez : 1/29/2004<br>alopez : 1/29/2004<br>alopez : 1/29/2004<br>tkritzer : 12/17/2003<br>tkritzer : 12/11/2003<br>terry : 12/8/2003<br>tkritzer : 11/6/2003<br>tkritzer : 11/5/2003<br>terry : 11/3/2003<br>alopez : 1/6/2003<br>tkritzer : 7/25/2002<br>tkritzer : 7/25/2002<br>alopez : 3/16/2001<br>mgross : 2/23/2000<br>carol : 7/20/1998<br>carol : 7/17/1998<br>dholmes : 7/16/1998<br>mark : 12/10/1997<br>alopez : 7/29/1997<br>alopez : 7/10/1997<br>terry : 7/7/1997<br>jenny : 5/21/1997<br>jenny : 5/21/1997<br>mimadm : 11/5/1994<br>supermim : 3/16/1992<br>carol : 1/18/1991<br>carol : 7/6/1990
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>#</strong> 146110
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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HYPOGONADOTROPIC HYPOGONADISM 7 WITH OR WITHOUT ANOSMIA; HH7
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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HYPOGONADISM, ISOLATED HYPOGONADOTROPIC<br />
|
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IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; IHH
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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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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 123953004;
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<strong>ORPHA:</strong> 432;
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<strong>DO:</strong> 0090078;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
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</h4>
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
|
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Phenotype <br /> MIM number
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</th>
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<th>
|
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Inheritance
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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<th>
|
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Gene/Locus
|
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</th>
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<th>
|
|
Gene/Locus <br /> MIM number
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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>
|
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<span class="mim-font">
|
|
4q13.2
|
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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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146110
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
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">
|
|
3
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
GNRHR
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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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138850
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because hypogonadotropic hypogonadism-7 with or without anosmia (HH7) is caused by homozygous or compound heterozygous mutation in the GNRHR gene (138850) on chromosome 4q13, sometimes in association with mutation in another gene, e.g., FGFR1 (136350).</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>Description</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' </p><p>For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.</p>
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<strong>Clinical Features</strong>
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<p>De Roux et al. (1997) studied a brother and sister with normosmic hypogonadotropic hypogonadism. The 22-year-old propositus was referred because of hypogonadism and impaired libido, who had undergone puberty at age 16. His height was 180 cm and his arm span 186 cm. Physical examination revealed absence of facial hair, sparse pubic hair (Tanner stage 3), and a penis of 6 cm. He had scrotal testes, and the volume of each was 8 ml (normal, 15 to 25 ml). There was no gynecomastia. He had a normal sense of smell and no mirror movements of the upper limbs, no abnormal eye movements, no colorblindness, and no renal or craniofacial abnormalities. The karyotype was 46,XY. The patient's 37-year-old sister had a history of primary amenorrhea and infertility. Spontaneous thelarche had occurred at age 14 years. She had a single episode of uterine bleeding at age 18, and afterward received combined oral contraceptive treatment. This treatment was interrupted when she desired children. However, amenorrhea and absence of pregnancy led to ovulation-inducing treatment, which resulted in 2 normal pregnancies and the births of a girl and a boy, 4 and 7 years old at the time of report. After each pregnancy, she had persistent amenorrhea, and oral contraceptive treatment was resumed. Her height was 165 cm. Pubic hair development was at Tanner stage 5, and her breasts and external genitalia were those of a normal woman. Both parents and a sister were clinically and endocrinologically normal. </p><p>Caron et al. (1999) studied 3 sibs with mutations in GNRHR from a kindred with isolated hypogonadotropic hypogonadism. The 2 brothers, who were referred for lack of puberty, had microphallus and bilateral cryptorchidism; their sister had primary amenorrhea and a complete lack of puberty. The authors concluded that these hypogonadal patients were partially resistant to pulsatile GNRH administration, suggesting that they should instead be treated with gonadotropins to induce spermatogenesis or ovulation. </p><p>Pitteloud et al. (2001) reported a 26-year-old male with a mild form of hypogonadotropic hypogonadism, which they called a 'fertile eunuch variant' of HH. The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with chorionic gonadotropin (CG; see 118860) alone, he developed sperm in his ejaculate, and his wife conceived. Following cessation of CG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone (LH; see 152780) secretion. The authors concluded that this case expanded the clinical spectrum of GNRHR mutations, providing the first genetic basis for the fertile eunuch variant of hypogonadotropic hypogonadism and documenting the occurrence of reversible hypogonadotropic hypogonadism in a patient with a GNRHR mutation. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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De Roux et al. (1999) performed detailed endocrinologic studies in 3 affected members of a family with hypogonadotropic hypogonadism who had mutations in GNRHR (see MOLECULAR GENETICS). The proband, a 30-year-old male, had complete HH with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha subunit (see 152780), absence of response to GNRH (152760) and GNRH agonist (triptorelin), and absence of effect of pulsatile administration of GNRH. His affected 18- and 24-year-old sisters had only partial hypogonadotropic hypogonadism. They both had primary amenorrhea and normal breast development, but the younger sister had retarded bone maturation and uterus development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GNRH. In both sisters, there were no spontaneous pulses of LH, but pulsatile administration of GNRH provoked pulsatile secretion of LH in the younger one. The authors concluded that the same GNRHR mutations may exhibit varying degrees of alteration of gonadotropin function in affected members of the same family. </p>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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<span class="mim-text-font">
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<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. 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, and that the findings demonstrated the efficacy of an approach based on pharmacologic rescue and suggested the basis of new approaches for intervention in this and similar disorders. </p>
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<h4>
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<strong>Inheritance</strong>
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<p>The transmission pattern of hypogonadotropic hypogonadism in the family reported by de Roux et al. (1997) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>In a brother and sister with normosmic hypogonadotropic hypogonadism, 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, including 32 males at least 18 years of age and 14 females at least 17 years of age, and identified compound heterozygosity for the R262Q mutation and another missense mutation (Y284C; 138850.0003) in 1 family with 4 affected sibs. At least 1 of the affected females ovulated in response to exogenous gonadotropins. </p><p>In 3 sibs from a kindred with isolated HH, Caron et al. (1999) identified compound heterozygosity for the R262Q mutation and another missense mutation in GNRHR (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 3 missense mutations in the GNRHR gene, with R262Q on 1 allele, and Q106R and S217R (138850.0005) on the other allele. Endocrinologic analysis demonstrated varying degrees of alteration of gonadotropin function in the 3 sibs, although they all carried the same mutations. </p><p>In a male patient with complete HH, who presented with primary failure of pulsatile GNRH (152760) therapy but responded to exogenous gonadotropin administration, Pralong et al. (1999) identified homozygosity for a missense mutation in the GNRHR gene (S168R; 138850.0006). </p><p>In a woman with complete HH, Kottler et al. (2000) identified compound heterozygosity for Q106R and a nonsense mutation (L314X; 138850.0007) in the GNRHR gene. </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, 10 males and 7 females, from 14 different families with normosmic hypogonadotropic hypogonadism. The diagnosis of HH was based on absent or incomplete sexual development after 17 years of age associated with low or normal levels of LH in both sexes and low levels of testosterone in males and of estradiol in females. All patients presented with a normal sense of smell in an olfactory-specific test. In 1 female patient with complete HH, who had undetectable serum basal LH and FSH levels that failed to respond to GNRH stimulation, Costa et al. (2001) identified homozygosity for a missense mutation in the GNRHR gene (R139H; 138850.0008). In 4 sibs with partial HH, who had low serum basal LH levels that were responsive to GNRH stimulation, they identified compound heterozygosity for the Q106R mutation and another missense mutation in GNRHR (N10K; 138850.0009). </p><p>In a woman with primary amenorrhea and absent thelarche and pubarche, Silveira et al. (2002) identified homozygosity for a splice site mutation (138850.0011). The patient had no spontaneous gonadotropin pulsatility and did not respond to either exogenous pulsatile or acute GNRH administration, but exogenous gonadotropin administration resulted in a normal pregnancy. </p><p>Meysing et al. (2004) reported a normosmic female patient with congenital idiopathic HH in whom treatment with pulsatile GNRH resulted in an unusual response: she 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. Analysis of the GNRHR coding sequence revealed compound heterozygous GNRHR mutations (138850.0013 and 138850.0014). </p><p>In 2 brothers with HH, Lin et al. (2006) reported homozygosity for the R262Q mutation in GNRHR. The proband presented at 15 years of age with delayed puberty. After a short course of testosterone, he seemed to be progressing through puberty appropriately and was discharged from follow-up. His younger brother was also referred with delayed puberty but showed little progress after treatment. Lin et al. (2006) concluded that homozygous partial loss-of-function mutations in GNRHR such as R262Q can present with variable phenotypes, including apparent delayed puberty. </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, 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 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><p><strong><em>Possible Association with Functional Hypothalamic Amenorrhea in Carrier Females</em></strong></p><p>
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Caronia et al. (2011) studied 55 women with functional hypothalamic amenorrhea, who had all completed puberty spontaneously and had a history of secondary amenorrhea for 6 months or more, with low or normal gonadotropin levels and low serum estradiol levels. All had 1 or more predisposing factors, including excessive exercise, loss of more than 15% of body weight, and/or a subclinical eating disorder, and all had normal results on neuroimaging. The authors screened 7 HH-associated genes in the 55 affected women and identified 7 patients from 6 families who carried heterozygous mutations, including 1 in KAL1, 2 in FGFR1, 2 in PROKR2 (607123), and 1 in the GNRHR gene. Since these women with mutations resumed regular menses after discontinuing hormone-replacement therapy, Caronia et al. (2011) concluded that the genetic component of hypothalamic amenorrhea predisposes patients to, but is not sufficient to cause, GnRH deficiency. </p>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<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 gene. 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. </p><p>Bhagavath et al. (2005) analyzed DNA from 185 HH patients and identified compound heterozygous GNRHR mutations in 3 (1.6%). All 3 were Caucasian, from a cohort of 85 HH patients with documented normosmia, and both the male patients as well as the female patient had so-called 'complete' HH, in which there is no evidence of steroid production as evidenced by a completely prepubertal phenotype. No mutations were found in the hyposmic or anosmic HH patients. GNRHR mutations were identified in 1 (6.7%) of 15 families with at least 2 affected sibs and in 2 (11.1%) of 18 normosmic HH females. No mutations were found in presumed autosomal dominant families. Bhagavath et al. (2005) concluded that GNRHR mutations account for approximately 3.5% of all normosmic HH and 7 to 11% of presumed autosomal recessive HH, suggesting that additional genes play an important role in normal puberty. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<p class="mim-text-font">
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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>
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|
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">
|
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Bhagavath, B., Ozata, M., Ozdemir, I. C., Bolu, E., Bick, D. P., Sherins, R. J., Layman, L. C.
|
|
<strong>The prevalence of gonadotropin-releasing hormone receptor mutations in a large cohort of patients with hypogonadotropic hypogonadism.</strong>
|
|
Fertil. Steril. 84: 951-957, 2005.
|
|
|
|
|
|
[PubMed: 16213849]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.fertnstert.2005.04.029]
|
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|
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|
</p>
|
|
</li>
|
|
|
|
<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.
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|
<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]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.3.5518]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., Avbelj, M., Dhruvakumar, S., Plummer, L., Hughes, V. A., Seminara, S. B., Boepple, P. A., Sidis, Y., Crowley, W. F., Jr., Martin, K. A., Hall, J. E., Pitteloud, N.
|
|
<strong>A genetic basis for functional hypothalamic amenorrhea.</strong>
|
|
New Eng. J. Med. 364: 215-225, 2011.
|
|
|
|
|
|
[PubMed: 21247312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0911064]
|
|
|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Costa, E. M. F., Bedecarrats, G. Y., Mendonca, B. B., Arnhold, I. J. P., Kaiser, U. B., Latronico, A. C.
|
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<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]
|
|
|
|
|
|
[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">
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de Roux, N., Young, J., Brailly-Tabard, S., Misrahi, M., Milgrom, E., Schaison, G.
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<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: 10022417]
|
|
|
|
|
|
[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>
|
|
<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">
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Janovick, J. A., Maya-Nunez, G., Conn, P. M.
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|
<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">
|
|
Kottler, M.-L., Chauvin, S., Lahlou, N., Harris, C. E., Johnston, C. J., Lagarde, J.-P., Bouchard, P., Farid, N. R., Counis, R.
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|
<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]
|
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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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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]
|
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</p>
|
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</li>
|
|
|
|
<li>
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<p class="mim-text-font">
|
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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]
|
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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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Lin, L, Conway, G. S, Hill, N. R, Dattani, M. T, Hindmarsh, P. C, Achermann, J. C.
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<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.
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|
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|
|
[PubMed: 16968799]
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[Full Text: https://doi.org/10.1210/jc.2006-0807]
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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]
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Pitteloud, N., Boepple, P. A., DeCruz, S., Valkenburgh, S. B., Crowley, W. F., Jr., Hayes, F. J.
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<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]
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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.
|
|
|
|
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[PubMed: 17235395]
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|
|
|
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[Full Text: https://doi.org/10.1172/JCI29884]
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Pralong, F. P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M. L., Portmann, L., Gaillard, R. C.
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<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.
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|
|
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|
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[PubMed: 10523035]
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|
|
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[Full Text: https://doi.org/10.1210/jcem.84.10.6042]
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Raivio, T., Falardeau, J., Dwyer, A., Quinton, R., Hayes, F. J., Hughes, V. A., Cole, L. W., Pearce, S. H., Lee, H., Boepple, P., Crowley, W. F., Jr., Pitteloud, N.
|
|
<strong>Reversal of idiopathic hypogonadotropic hypogonadism.</strong>
|
|
New Eng. J. Med. 357: 863-873, 2007.
|
|
|
|
|
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[PubMed: 17761590]
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[Full Text: https://doi.org/10.1056/NEJMoa066494]
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Seminara, S. B., Beranova, M., Oliveira, L. M. B., Martin, K. A., Crowley, W. F., Jr., Hall, J. E.
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<strong>Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.</strong>
|
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J. Clin. Endocr. Metab. 85: 556-562, 2000.
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[PubMed: 10690855]
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[Full Text: https://doi.org/10.1210/jcem.85.2.6357]
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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: 12050282]
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[Full Text: https://doi.org/10.1210/jcem.87.6.8535]
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Marla J. F. O'Neill - updated : 04/06/2017<br>Marla J. F. O'Neill - updated : 2/9/2016<br>Marla J. F. O'Neill - updated : 3/25/2015<br>Marla J. F. O'Neill - updated : 10/19/2012<br>Marla J. F. O'Neill - updated : 10/11/2012<br>Marla J. F. O'Neill - updated : 9/27/2012<br>Marla J. F. O'Neill - updated : 2/23/2012<br>Marla J. F. O'Neill - updated : 7/14/2009<br>Marla J. F. O'Neill - updated : 4/30/2009<br>Marla J. F. O'Neill - updated : 3/23/2009<br>Marla J. F. O'Neill - updated : 10/31/2008<br>Marla J. F. O'Neill - updated : 10/8/2008<br>Marla J. F. O'Neill - updated : 3/13/2007<br>John A. Phillips, III - updated : 8/21/2006<br>Marla J. F. O'Neill - updated : 6/2/2006<br>John A. Phillips, III - updated : 1/29/2004<br>John A. Phillips, III - updated : 1/29/2004<br>Victor A. McKusick - updated : 12/8/2003<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 1/6/2003<br>John A. Phillips, III - updated : 7/25/2002<br>John A. Phillips, III - updated : 2/23/2000<br>John A. Phillips, III - updated : 7/16/1998<br>John A. Phillips, III - updated : 12/20/1996
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