2591 lines
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Entry
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- #215470 - BOUCHER-NEUHAUSER SYNDROME; BNHS
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- OMIM
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<p>
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<span class="h4">#215470</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 role="presentation">
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<a href="/clinicalSynopsis/215470"><strong>Clinical Synopsis</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="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<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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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=BOUCHER-NEUHAUSER SYNDROME" 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=1438&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/NBK247161/" 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/902" 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://medlineplus.gov/genetics/condition/boucher-neuhauser-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=215470[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=1180" 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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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/670181c4-e046-4f3d-9527-d50654aa78fe/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0111265" 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/215470" 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:0111265" 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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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715984007<br />
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<strong>ORPHA:</strong> 1180<br />
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<strong>DO:</strong> 0111265<br />
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">ICD+</a>
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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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215470
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</span>
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</span>
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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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BOUCHER-NEUHAUSER SYNDROME; BNHS
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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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SPINOCEREBELLAR ATAXIA, HYPOGONADOTROPIC HYPOGONADISM, AND CHORIORETINAL DYSTROPHY
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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">
|
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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 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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<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/19/207?start=-3&limit=10&highlight=207">
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19p13.2
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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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Boucher-Neuhauser syndrome
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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/215470"> 215470 </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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PNPLA6
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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/603197"> 603197 </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/215470" 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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<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/215470" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/215470" 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> Eyes </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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|
|
- Choroidal dystrophy (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312918002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312918002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0730291&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0730291</a>]</span><br /> -
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Retinal dystrophy (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/314407005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">314407005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0854723&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0854723</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000556</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000556</a>]</span><br /> -
|
|
Visual loss, progressive (in most patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839364&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839364</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000529" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000529</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000529" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000529</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H54.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H54.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/369.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">369.9</a>]</span><br /> -
|
|
Photophobia (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409668002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409668002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246622003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246622003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</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> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hypogonadism, hypogonadotropic <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33927004</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>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271623</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><br />
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|
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</span>
|
|
</div>
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Distal muscle wasting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848736&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848736</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</a>]</span><br />
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|
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</span>
|
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</div>
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|
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cerebellar ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
|
|
Scanning speech <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77420001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77420001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240952&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240952</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002168" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002168</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002168" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002168</a>]</span><br /> -
|
|
Intention tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30721006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30721006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551520</a>, <a href="https://bioportal.bioontology.org/search?q=C0234376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234376</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002345" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002345</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002080" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002080</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002080" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002080</a>]</span><br /> -
|
|
Spasticity (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
|
|
Upper motor neuron signs (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0749870&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0749870</a>]</span><br /> -
|
|
Mild cognitive impairment (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386805003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386805003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G31.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G31.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1270972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1270972</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br /> -
|
|
Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</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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<span class="h5 mim-font">
|
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<em> Peripheral Nervous System </em>
|
|
</span>
|
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</div>
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- Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
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Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
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Sensorimotor axonal neuropathy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230657007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230657007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0393907&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393907</a>]</span><br />
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<strong> ENDOCRINE FEATURES </strong>
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- Hypogonadotropic hypogonadism <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> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271623</a>, <a href="https://bioportal.bioontology.org/search?q=C0022735&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022735</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><br /> -
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Hypothalamic dysfunction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111568001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111568001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751230</a>]</span><br /> -
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Delay in secondary sexual characteristics <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859094&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859094</a>]</span><br />
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</span>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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<div style="margin-left: 2em;">
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- Decreased plasma gonadotrophin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859095&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859095</a>]</span><br />
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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<div style="margin-left: 2em;">
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- Some features are variable, even within families<br /> -
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Neurologic signs onset during adolescence or young adulthood<br /> -
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Ophthalmologic signs onset in first to sixth decade<br /> -
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Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
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Some patients become wheelchair-bound<br />
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</span>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the patatin-like phospholipase domain-containing protein 6 (PNPLA6, <a href="/entry/603197#0004">603197.0004</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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<div>
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<br />
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Boucher-Neuhauser syndrome (BNHS) is caused by homozygous or compound heterozygous mutation in the PNPLA6 gene (<a href="/entry/603197">603197</a>) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Boucher-Neuhauser syndrome (BNHS) is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39; <a href="/entry/612020">612020</a>) (summary by <a href="#8" class="mim-tip-reference" title="Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., Durr, A., Schols, L., Lima-Martinez, M. M., Farooq, A., Schule, R., Stevanin, G., Marques, W., Jr., Zuchner, S. <strong>PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.</strong> Brain 137: 69-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24355708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24355708</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24355708[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/10.1093/brain/awt326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24355708">Synofzik et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24355708" 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>See also Gordon Holmes syndrome (GDHS; <a href="/entry/212840">212840</a>), caused by mutation in the RNF216 gene (<a href="/entry/609948">609948</a>), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism.</p>
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Clinical Features</strong>
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<p><a href="#5" class="mim-tip-reference" title="Neuhauser, G., Opitz, J. M. <strong>Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism.</strong> Clin. Genet. 7: 426-434, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1149314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1149314</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1975.tb00353.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1149314">Neuhauser and Opitz (1975)</a> described a kindred in which 2 brothers and 2 sisters with second-cousin parents had cerebellar ataxia in association with hypogonadotropic hypogonadism. In 3 sibs the onset of cerebellar ataxia was between 12 and 20 years and in the fourth, in the 30s. Hypogonadotropism was reflected in failure of secondary sexual characteristics, eunuchoidism, absence of libido, and infertility. <a href="#4" class="mim-tip-reference" title="Limber, E. R., Bresnick, G. H., Lebovitz, R. M., Appen, R. E., Gilbert-Barness, E. F., Pauli, R. M. <strong>Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhauser syndrome).</strong> Am. J. Med. Genet. 33: 409-414, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2801777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2801777</a>] [<a href="https://doi.org/10.1002/ajmg.1320330325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2801777">Limber et al. (1989)</a> provided a follow-up on the family described by Neuhauser and Opitz (1975) and demonstrated that the affected members had a syndrome that included, in addition to spinocerebellar ataxia and hypogonadotropic hypogonadism, chorioretinal dystrophy. <a href="#4" class="mim-tip-reference" title="Limber, E. R., Bresnick, G. H., Lebovitz, R. M., Appen, R. E., Gilbert-Barness, E. F., Pauli, R. M. <strong>Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhauser syndrome).</strong> Am. J. Med. Genet. 33: 409-414, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2801777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2801777</a>] [<a href="https://doi.org/10.1002/ajmg.1320330325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2801777">Limber et al. (1989)</a> also reported another family in which a brother and sister had cerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy, and noted that an earlier example of this triad had been reported by <a href="#2" class="mim-tip-reference" title="Boucher, B. J., Gibberd, F. B. <strong>Familial ataxia, hypogonadism and retinal degeneration.</strong> Acta Neurol. Scand. 45: 507-510, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5806782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5806782</a>]" pmid="5806782">Boucher and Gibberd (1969)</a> in 2 affected sisters. <a href="#4" class="mim-tip-reference" title="Limber, E. R., Bresnick, G. H., Lebovitz, R. M., Appen, R. E., Gilbert-Barness, E. F., Pauli, R. M. <strong>Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhauser syndrome).</strong> Am. J. Med. Genet. 33: 409-414, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2801777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2801777</a>] [<a href="https://doi.org/10.1002/ajmg.1320330325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2801777">Limber et al. (1989)</a> recognized the association of spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy as an autonomous single-gene disorder and called it Boucher-Neuhauser syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1149314+2801777+5806782" 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="Fok, A. C. K., Wong, M. C., Cheah, J. S. <strong>Syndrome of cerebellar ataxia and hypogonadotropic hypogonadism: evidence for pituitary gonadotrophin deficiency.</strong> J. Neurol. Neurosurg. Psychiat. 52: 407-409, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494301</a>] [<a href="https://doi.org/10.1136/jnnp.52.3.407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2494301">Fok et al. (1989)</a> reported a Chinese male with cerebellar ataxia, hypogonadotropic hypogonadism, and peripapillary degeneration with chorioretinal atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2494301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Baroncini, A., Franco, N., Forabosco, A. <strong>A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhauser syndrome).</strong> Clin. Genet. 39: 274-277, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906382</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1991.tb03025.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1906382">Baroncini et al. (1991)</a> described affected brothers. A review of reported cases indicated that the neurologic signs usually develop during adolescence or early adulthood (range, early childhood to the fourth decade) and are slowly progressive or nonprogressive, whereas ophthalmologic manifestations have an age of onset that varies from the first to the sixth decade of life and a pronounced variability in progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Salvador, F., Garcia-Arumi, J., Corcostegui, B., Minoves, T., Tarrus, F. <strong>Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy.</strong> Am. J. Ophthal. 120: 241-244, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7639308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7639308</a>] [<a href="https://doi.org/10.1016/s0002-9394(14)72612-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7639308">Salvador et al. (1995)</a> reported the ophthalmologic findings in a 39-year-old woman with this disorder. Puberty had been delayed although menarche occurred and secondary sex characteristics developed with hormone injections at 17 years of age. Menstruation ceased when the medication was discontinued 4 years later. At 28 years of age, the patient experienced progressive deterioration of balance, and at age 32 years, scanning speech and intention tremor appeared. MRI showed diffuse atrophy of the cerebellar hemispheres. Progressive loss of vision and photophobia began at the age of 37 years. Ophthalmoscopy showed extensive atrophic changes of the retinal pigment epithelium and choriocapillaris in the posterior pole and midperiphery of both eyes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7639308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A. <strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong> J. Med. Genet. 34: 767-771, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321767</a>] [<a href="https://doi.org/10.1136/jmg.34.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9321767">Rump et al. (1997)</a> described 2 sibs from a nonconsanguineous family with this disorder and reviewed 17 previously reported cases. <a href="#6" class="mim-tip-reference" title="Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A. <strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong> J. Med. Genet. 34: 767-771, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321767</a>] [<a href="https://doi.org/10.1136/jmg.34.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9321767">Rump et al. (1997)</a> considered the presence of features additional to the triad of chorioretinal dystrophy, hypogonadotropic hypogonadism, and spinal cerebellar ataxia likely to intimate a different diagnosis. They also pointed out that the onset of neurologic symptoms may be delayed until the third decade of life and may be variable in nature, hence making the diagnosis difficult. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9321767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., Durr, A., Schols, L., Lima-Martinez, M. M., Farooq, A., Schule, R., Stevanin, G., Marques, W., Jr., Zuchner, S. <strong>PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.</strong> Brain 137: 69-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24355708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24355708</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24355708[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/10.1093/brain/awt326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24355708">Synofzik et al. (2014)</a> reported 4 Brazilian sibs, born of consanguineous parents, with Boucher-Neuhauser syndrome. All presented with visual impairment due to chorioretinal dystrophy within the first 3 years of life. Gait ataxia without spasticity developed around age 6 to 7 years. All patients also had hypogonadotropic hypogonadism, including primary amenorrhea in females. Other features included distal muscle wasting, hyporeflexia, and mild cognitive impairment. Brain MRI showed an atrophic pons and cerebellum, as well as a small pituitary. The patients were between 48 and 56 years of age at the time of the report. Five patients from 3 additional families with BNHS were also identified, and all of these patients were adults at the time of the report. The phenotype was somewhat variable: in an Italian family, 1 sister presented at age 12 with visual impairment due to chorioretinal dystrophy, whereas the other sister presented at age 6 with gait ataxia but never developed chorioretinal dystrophy. Both had mild cognitive impairment, hypogonadotropic hypogonadism, and signs of spasticity. In a Brazilian family, 2 brothers presented at age 6 with gait ataxia, and were later found to have chorioretinal dystrophy and hypogonadotropic hypogonadism. Both had normal cognition. A Venezuelan patient was noted to have delayed puberty and visual impairment at age 14; gait ataxia developed around age 20. He did not have cognitive impairment or spasticity. A French man from a fourth family presented with delayed puberty at age 14 and developed gait ataxia in his thirties. He did not have chorioretinal atrophy and had been clinically diagnosed with Gordon Holmes syndrome (<a href="/entry/212840">212840</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24355708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., Eren, E., Mengen, E., Gurbuz, F., Cook, M., Castellano, J. M., Kekil, M. B., Mungan, N. O., Yuksel, B., Ojeda, S. R. <strong>Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.</strong> J. Clin. Endocr. Metab. 99: E2067-E2075, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25033069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25033069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25033069[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.2014-1836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25033069">Topaloglu et al. (2014)</a> reported 6 patients from 3 unrelated families with pubertal failure and ataxia who carried biallelic mutations in the PNPLA6 gene. One of the families, of Dutch descent, had previously been reported by <a href="#6" class="mim-tip-reference" title="Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A. <strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong> J. Med. Genet. 34: 767-771, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321767</a>] [<a href="https://doi.org/10.1136/jmg.34.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9321767">Rump et al. (1997)</a>. The other 2 families were Turkish. All patients had primary pubertal failure with variable onset of unsteady gait and dysarthria; all had a normal sense of smell. The Turkish patients had no ophthalmologic features, suggesting that such features are not always observed in patients with PNPLA6 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25033069+9321767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Baroncini, A., Franco, N., Forabosco, A. <strong>A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhauser syndrome).</strong> Clin. Genet. 39: 274-277, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906382</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1991.tb03025.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1906382">Baroncini et al. (1991)</a> suggested autosomal recessive inheritance for this disorder because cases had been reported in sibs in a single generation with unaffected parents and consanguinity was identified in 1 instance; males and females were equally affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906382" 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 9 patients from 4 unrelated families with Boucher-Neuhauser syndrome, <a href="#8" class="mim-tip-reference" title="Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., Durr, A., Schols, L., Lima-Martinez, M. M., Farooq, A., Schule, R., Stevanin, G., Marques, W., Jr., Zuchner, S. <strong>PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.</strong> Brain 137: 69-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24355708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24355708</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24355708[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/10.1093/brain/awt326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24355708">Synofzik et al. (2014)</a> identified homozygous or compound heterozygous mutations in the PNPLA6 gene (see, e.g., <a href="/entry/603197#0004">603197.0004</a>-<a href="/entry/603197#0008">603197.0008</a>). All mutations occurred at highly conserved residues and were predicted to disrupt protein function, but in vitro functional studies of the variants were not performed. The mutations in the first 2 families were found by whole-exome sequencing, whereas mutations in the second 2 families were found by direct sequencing of the PNPLA6 gene in 4 additional families with the disorder. A patient from a fifth family who did not have chorioretinopathy also carried biallelic PNPLA6 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24355708" 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 6 patients from 3 unrelated families with BNHS, <a href="#9" class="mim-tip-reference" title="Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., Eren, E., Mengen, E., Gurbuz, F., Cook, M., Castellano, J. M., Kekil, M. B., Mungan, N. O., Yuksel, B., Ojeda, S. R. <strong>Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.</strong> J. Clin. Endocr. Metab. 99: E2067-E2075, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25033069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25033069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25033069[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.2014-1836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25033069">Topaloglu et al. (2014)</a> identified homozygous or compound heterozygous mutations in the PNPLA6 gene (see, e.g., <a href="/entry/603197#0011">603197.0011</a>-<a href="/entry/603197#0012">603197.0012</a>). One of the families had previously been reported by <a href="#6" class="mim-tip-reference" title="Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A. <strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong> J. Med. Genet. 34: 767-771, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321767</a>] [<a href="https://doi.org/10.1136/jmg.34.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9321767">Rump et al. (1997)</a>. The mutation in the first family was found by homozygosity mapping and whole-exome sequencing; subsequent mutations were found by direct sequencing of the PNPLA6 gene in 5 additional families. The mutations failed to rescue the neurodegenerative 'Sws' vacuolization phenotype in Drosophila with loss of Pnpla6. Inhibition of NTE activity in a mouse gonadotrope cell line inhibited GNRH (<a href="/entry/152760">152760</a>)-stimulated luteinizing hormone (LH) exocytosis, without affecting GNRH receptor (GNRHR; <a href="/entry/138850">138850</a>) signaling or LH-beta (LHB; <a href="/entry/152780">152780</a>) synthesis. The findings were consistent with the mutations resulting in a loss of function. Some patients did not have chorioretinopathy, a finding more consistent with a clinical diagnosis of Gordon Holmes syndrome; <a href="#9" class="mim-tip-reference" title="Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., Eren, E., Mengen, E., Gurbuz, F., Cook, M., Castellano, J. M., Kekil, M. B., Mungan, N. O., Yuksel, B., Ojeda, S. R. <strong>Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.</strong> J. Clin. Endocr. Metab. 99: E2067-E2075, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25033069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25033069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25033069[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.2014-1836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25033069">Topaloglu et al. (2014)</a> noted that GDHS and BNHS are phenotypically related. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25033069+9321767" 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>A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhauser syndrome).</strong>
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Clin. Genet. 39: 274-277, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906382</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1991.tb03025.x" 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="2" class="mim-anchor"></a>
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<a id="Boucher1969" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Boucher, B. J., Gibberd, F. B.
|
|
<strong>Familial ataxia, hypogonadism and retinal degeneration.</strong>
|
|
Acta Neurol. Scand. 45: 507-510, 1969.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5806782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5806782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5806782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Fok1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Fok, A. C. K., Wong, M. C., Cheah, J. S.
|
|
<strong>Syndrome of cerebellar ataxia and hypogonadotropic hypogonadism: evidence for pituitary gonadotrophin deficiency.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 52: 407-409, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2494301" 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/10.1136/jnnp.52.3.407" 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="4" class="mim-anchor"></a>
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<a id="Limber1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Limber, E. R., Bresnick, G. H., Lebovitz, R. M., Appen, R. E., Gilbert-Barness, E. F., Pauli, R. M.
|
|
<strong>Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhauser syndrome).</strong>
|
|
Am. J. Med. Genet. 33: 409-414, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2801777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2801777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2801777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320330325" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Neuhauser1975" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Neuhauser, G., Opitz, J. M.
|
|
<strong>Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism.</strong>
|
|
Clin. Genet. 7: 426-434, 1975.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1149314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1149314</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1149314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1975.tb00353.x" 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="6" class="mim-anchor"></a>
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<a id="Rump1997" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A.
|
|
<strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong>
|
|
J. Med. Genet. 34: 767-771, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321767</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9321767" 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/10.1136/jmg.34.9.767" 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="7" class="mim-anchor"></a>
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<a id="Salvador1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Salvador, F., Garcia-Arumi, J., Corcostegui, B., Minoves, T., Tarrus, F.
|
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<strong>Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy.</strong>
|
|
Am. J. Ophthal. 120: 241-244, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7639308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7639308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7639308" 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/s0002-9394(14)72612-1" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Synofzik2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., Durr, A., Schols, L., Lima-Martinez, M. M., Farooq, A., Schule, R., Stevanin, G., Marques, W., Jr., Zuchner, S.
|
|
<strong>PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.</strong>
|
|
Brain 137: 69-77, 2014.
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24355708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24355708</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24355708[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=24355708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awt326" 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="9" class="mim-anchor"></a>
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<a id="Topaloglu2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., Eren, E., Mengen, E., Gurbuz, F., Cook, M., Castellano, J. M., Kekil, M. B., Mungan, N. O., Yuksel, B., Ojeda, S. R.
|
|
<strong>Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.</strong>
|
|
J. Clin. Endocr. Metab. 99: E2067-E2075, 2014. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25033069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25033069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25033069[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=25033069" 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.2014-1836" target="_blank">Full Text</a>]
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</p>
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</div>
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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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Cassandra L. Kniffin - updated : 10/13/2014
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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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Cassandra L. Kniffin - updated : 2/24/2014<br>Marla J. F. O'Neill - updated : 6/6/2013<br>Michael J. Wright - updated : 2/11/1998
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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 : 12/12/1991
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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 : 01/04/2023
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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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alopez : 02/09/2015<br>carol : 10/20/2014<br>mcolton : 10/14/2014<br>ckniffin : 10/13/2014<br>alopez : 3/4/2014<br>mcolton : 2/25/2014<br>ckniffin : 2/24/2014<br>carol : 6/6/2013<br>carol : 8/16/2012<br>mgross : 3/17/2004<br>alopez : 2/18/1998<br>terry : 2/11/1998<br>mark : 10/16/1995<br>mimadm : 2/19/1994<br>supermim : 3/16/1992<br>carol : 12/12/1991
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</span>
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<div class="container visible-print-block">
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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> 215470
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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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BOUCHER-NEUHAUSER SYNDROME; BNHS
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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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<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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SPINOCEREBELLAR ATAXIA, HYPOGONADOTROPIC HYPOGONADISM, AND CHORIORETINAL DYSTROPHY
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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> 715984007;
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<strong>ORPHA:</strong> 1180;
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<strong>DO:</strong> 0111265;
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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>
|
|
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>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
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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19p13.2
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Boucher-Neuhauser syndrome
|
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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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215470
|
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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">
|
|
PNPLA6
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
603197
|
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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">
|
|
<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 Boucher-Neuhauser syndrome (BNHS) is caused by homozygous or compound heterozygous mutation in the PNPLA6 gene (603197) on chromosome 19p13.</p>
|
|
</span>
|
|
<div>
|
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<p>Boucher-Neuhauser syndrome (BNHS) is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39; 612020) (summary by Synofzik et al., 2014). </p><p>See also Gordon Holmes syndrome (GDHS; 212840), caused by mutation in the RNF216 gene (609948), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism.</p>
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<p>Neuhauser and Opitz (1975) described a kindred in which 2 brothers and 2 sisters with second-cousin parents had cerebellar ataxia in association with hypogonadotropic hypogonadism. In 3 sibs the onset of cerebellar ataxia was between 12 and 20 years and in the fourth, in the 30s. Hypogonadotropism was reflected in failure of secondary sexual characteristics, eunuchoidism, absence of libido, and infertility. Limber et al. (1989) provided a follow-up on the family described by Neuhauser and Opitz (1975) and demonstrated that the affected members had a syndrome that included, in addition to spinocerebellar ataxia and hypogonadotropic hypogonadism, chorioretinal dystrophy. Limber et al. (1989) also reported another family in which a brother and sister had cerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy, and noted that an earlier example of this triad had been reported by Boucher and Gibberd (1969) in 2 affected sisters. Limber et al. (1989) recognized the association of spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy as an autonomous single-gene disorder and called it Boucher-Neuhauser syndrome. </p><p>Fok et al. (1989) reported a Chinese male with cerebellar ataxia, hypogonadotropic hypogonadism, and peripapillary degeneration with chorioretinal atrophy. </p><p>Baroncini et al. (1991) described affected brothers. A review of reported cases indicated that the neurologic signs usually develop during adolescence or early adulthood (range, early childhood to the fourth decade) and are slowly progressive or nonprogressive, whereas ophthalmologic manifestations have an age of onset that varies from the first to the sixth decade of life and a pronounced variability in progression. </p><p>Salvador et al. (1995) reported the ophthalmologic findings in a 39-year-old woman with this disorder. Puberty had been delayed although menarche occurred and secondary sex characteristics developed with hormone injections at 17 years of age. Menstruation ceased when the medication was discontinued 4 years later. At 28 years of age, the patient experienced progressive deterioration of balance, and at age 32 years, scanning speech and intention tremor appeared. MRI showed diffuse atrophy of the cerebellar hemispheres. Progressive loss of vision and photophobia began at the age of 37 years. Ophthalmoscopy showed extensive atrophic changes of the retinal pigment epithelium and choriocapillaris in the posterior pole and midperiphery of both eyes. </p><p>Rump et al. (1997) described 2 sibs from a nonconsanguineous family with this disorder and reviewed 17 previously reported cases. Rump et al. (1997) considered the presence of features additional to the triad of chorioretinal dystrophy, hypogonadotropic hypogonadism, and spinal cerebellar ataxia likely to intimate a different diagnosis. They also pointed out that the onset of neurologic symptoms may be delayed until the third decade of life and may be variable in nature, hence making the diagnosis difficult. </p><p>Synofzik et al. (2014) reported 4 Brazilian sibs, born of consanguineous parents, with Boucher-Neuhauser syndrome. All presented with visual impairment due to chorioretinal dystrophy within the first 3 years of life. Gait ataxia without spasticity developed around age 6 to 7 years. All patients also had hypogonadotropic hypogonadism, including primary amenorrhea in females. Other features included distal muscle wasting, hyporeflexia, and mild cognitive impairment. Brain MRI showed an atrophic pons and cerebellum, as well as a small pituitary. The patients were between 48 and 56 years of age at the time of the report. Five patients from 3 additional families with BNHS were also identified, and all of these patients were adults at the time of the report. The phenotype was somewhat variable: in an Italian family, 1 sister presented at age 12 with visual impairment due to chorioretinal dystrophy, whereas the other sister presented at age 6 with gait ataxia but never developed chorioretinal dystrophy. Both had mild cognitive impairment, hypogonadotropic hypogonadism, and signs of spasticity. In a Brazilian family, 2 brothers presented at age 6 with gait ataxia, and were later found to have chorioretinal dystrophy and hypogonadotropic hypogonadism. Both had normal cognition. A Venezuelan patient was noted to have delayed puberty and visual impairment at age 14; gait ataxia developed around age 20. He did not have cognitive impairment or spasticity. A French man from a fourth family presented with delayed puberty at age 14 and developed gait ataxia in his thirties. He did not have chorioretinal atrophy and had been clinically diagnosed with Gordon Holmes syndrome (212840). </p><p>Topaloglu et al. (2014) reported 6 patients from 3 unrelated families with pubertal failure and ataxia who carried biallelic mutations in the PNPLA6 gene. One of the families, of Dutch descent, had previously been reported by Rump et al. (1997). The other 2 families were Turkish. All patients had primary pubertal failure with variable onset of unsteady gait and dysarthria; all had a normal sense of smell. The Turkish patients had no ophthalmologic features, suggesting that such features are not always observed in patients with PNPLA6 mutations. </p>
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<strong>Inheritance</strong>
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<p>Baroncini et al. (1991) suggested autosomal recessive inheritance for this disorder because cases had been reported in sibs in a single generation with unaffected parents and consanguinity was identified in 1 instance; males and females were equally affected. </p>
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<p>In 9 patients from 4 unrelated families with Boucher-Neuhauser syndrome, Synofzik et al. (2014) identified homozygous or compound heterozygous mutations in the PNPLA6 gene (see, e.g., 603197.0004-603197.0008). All mutations occurred at highly conserved residues and were predicted to disrupt protein function, but in vitro functional studies of the variants were not performed. The mutations in the first 2 families were found by whole-exome sequencing, whereas mutations in the second 2 families were found by direct sequencing of the PNPLA6 gene in 4 additional families with the disorder. A patient from a fifth family who did not have chorioretinopathy also carried biallelic PNPLA6 mutations. </p><p>In 6 patients from 3 unrelated families with BNHS, Topaloglu et al. (2014) identified homozygous or compound heterozygous mutations in the PNPLA6 gene (see, e.g., 603197.0011-603197.0012). One of the families had previously been reported by Rump et al. (1997). The mutation in the first family was found by homozygosity mapping and whole-exome sequencing; subsequent mutations were found by direct sequencing of the PNPLA6 gene in 5 additional families. The mutations failed to rescue the neurodegenerative 'Sws' vacuolization phenotype in Drosophila with loss of Pnpla6. Inhibition of NTE activity in a mouse gonadotrope cell line inhibited GNRH (152760)-stimulated luteinizing hormone (LH) exocytosis, without affecting GNRH receptor (GNRHR; 138850) signaling or LH-beta (LHB; 152780) synthesis. The findings were consistent with the mutations resulting in a loss of function. Some patients did not have chorioretinopathy, a finding more consistent with a clinical diagnosis of Gordon Holmes syndrome; Topaloglu et al. (2014) noted that GDHS and BNHS are phenotypically related. </p>
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<strong>REFERENCES</strong>
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<p class="mim-text-font">
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Baroncini, A., Franco, N., Forabosco, A.
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<strong>A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhauser syndrome).</strong>
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Clin. Genet. 39: 274-277, 1991.
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[PubMed: 1906382]
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[Full Text: https://doi.org/10.1111/j.1399-0004.1991.tb03025.x]
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Boucher, B. J., Gibberd, F. B.
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<strong>Familial ataxia, hypogonadism and retinal degeneration.</strong>
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Acta Neurol. Scand. 45: 507-510, 1969.
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[PubMed: 5806782]
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Fok, A. C. K., Wong, M. C., Cheah, J. S.
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<strong>Syndrome of cerebellar ataxia and hypogonadotropic hypogonadism: evidence for pituitary gonadotrophin deficiency.</strong>
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J. Neurol. Neurosurg. Psychiat. 52: 407-409, 1989.
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[PubMed: 2494301]
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[Full Text: https://doi.org/10.1136/jnnp.52.3.407]
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Limber, E. R., Bresnick, G. H., Lebovitz, R. M., Appen, R. E., Gilbert-Barness, E. F., Pauli, R. M.
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<strong>Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhauser syndrome).</strong>
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Am. J. Med. Genet. 33: 409-414, 1989.
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[PubMed: 2801777]
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[Full Text: https://doi.org/10.1002/ajmg.1320330325]
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Neuhauser, G., Opitz, J. M.
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<strong>Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism.</strong>
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Clin. Genet. 7: 426-434, 1975.
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[PubMed: 1149314]
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[Full Text: https://doi.org/10.1111/j.1399-0004.1975.tb00353.x]
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Rump, P., Hamel, B. C. J., Pinckers, A. J. L. G., van Dop, P. A.
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<strong>Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.</strong>
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J. Med. Genet. 34: 767-771, 1997.
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[PubMed: 9321767]
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[Full Text: https://doi.org/10.1136/jmg.34.9.767]
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Salvador, F., Garcia-Arumi, J., Corcostegui, B., Minoves, T., Tarrus, F.
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<strong>Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy.</strong>
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Am. J. Ophthal. 120: 241-244, 1995.
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[PubMed: 7639308]
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[Full Text: https://doi.org/10.1016/s0002-9394(14)72612-1]
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Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., Durr, A., Schols, L., Lima-Martinez, M. M., Farooq, A., Schule, R., Stevanin, G., Marques, W., Jr., Zuchner, S.
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<strong>PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.</strong>
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Brain 137: 69-77, 2014.
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[PubMed: 24355708]
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[Full Text: https://doi.org/10.1093/brain/awt326]
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Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., Eren, E., Mengen, E., Gurbuz, F., Cook, M., Castellano, J. M., Kekil, M. B., Mungan, N. O., Yuksel, B., Ojeda, S. R.
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<strong>Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.</strong>
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J. Clin. Endocr. Metab. 99: E2067-E2075, 2014. Note: Electronic Article.
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[PubMed: 25033069]
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[Full Text: https://doi.org/10.1210/jc.2014-1836]
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Cassandra L. Kniffin - updated : 10/13/2014<br>Cassandra L. Kniffin - updated : 2/24/2014<br>Marla J. F. O'Neill - updated : 6/6/2013<br>Michael J. Wright - updated : 2/11/1998
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Scientific Director, OMIM <br />
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