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Entry
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- #612292 - BIRK-BAREL SYNDROME; BIBARS
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- OMIM
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<p>
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<span class="h4">#612292</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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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#mapping">Mapping</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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<li role="presentation">
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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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</div>
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</a>
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</h4>
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</div>
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</div>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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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=BIRK-BAREL 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=17620&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/NBK425128/" 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/851" 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/kcnk9-imprinting-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=612292[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=166108" 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/256c03b1-e839-4e95-8d1d-247aedce5c31/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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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0050675" 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/612292" 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:0050675" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 764861005<br />
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<strong>ORPHA:</strong> 166108<br />
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<strong>DO:</strong> 0050675<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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612292
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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BIRK-BAREL SYNDROME; BIBARS
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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">
|
|
BIRK-BAREL MENTAL RETARDATION DYSMORPHISM SYNDROME<br />
|
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MENTAL RETARDATION WITH HYPOTONIA AND FACIAL DYSMORPHISM
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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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</tr>
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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/8/578?start=-3&limit=10&highlight=578">
|
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8q24.3
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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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Birk-Barel 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/612292"> 612292 </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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</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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KCNK9
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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/605874"> 605874 </a>
|
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</span>
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</td>
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</tr>
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<p>A number sign (#) is used with this entry because of evidence that Birk-Barel syndrome (BIBARS) is caused by heterozygous mutation in the KCNK9 gene (<a href="/entry/605874">605874</a>) on chromosome 8q24.</p>
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<p>Birk-Barel syndrome (BIBARS) is a paternally imprinted, autosomal dominant disorder characterized by motor and speech delay, impaired intellectual development, early feeding difficulties, muscular hypotonia, and behavioral abnormalities, including hyperactivity and aggression (summary by <a href="#2" class="mim-tip-reference" title="Cousin, M. A., Veale, E. L., Dsouza, N. R., Tripathi, S., Holden, R. G., Arelin, M., Beek, G., Bekheirnia, M. R., Beygo, J., Bhambhani, V., Bialer, M., Bigoni, S., and 59 others. <strong>Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.</strong> Genome Med. 14: 62, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35698242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35698242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35698242[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/10.1186/s13073-022-01064-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35698242">Cousin et al., 2022</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35698242" 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="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a> reported an Israeli-Arab kindred with an apparently maternally transmitted (imprinted with paternal silencing) syndrome of mental retardation, hypotonia, and characteristic dysmorphism. All affected individuals had moderate to severe mental retardation and were hyperactive. Severe feeding difficulties at infancy, requiring tube feeding in most, were followed in all patients by dysphagia of solid foods until near puberty. Generalized hypotonia at an early age was followed by weakness of proximal muscles and of the supra- and infrascapular and trapezius muscles. Coordination, tendon reflexes, deep and superficial sensation, and vibration were all normal. Babinski sign was negative. Hearing, vision, and ophthalmologic examination were normal. All affected individuals had similar dysmorphic features with most elements being more prominent at younger ages. The face was elongated with narrow bitemporal diameter, mild atrophy of temporalis and masseter muscles, and reduced facial movements. The eyebrows were flared, bushy, and arched upward, and downturned eyelids and congested conjunctivae were present in most patients. Ears were mildly protruding with a very prominent fold of the crux of the helix and a prominent antihelical fold. The nasal bridge was high and narrow with a broad nasal tip. The columella was normal, but the philtrum was extremely short, broad, and thick in all patients. The maxillary and premaxillary regions were prominent with hypotonia of the mandible and micrognathia, leading, in combination with the short philtrum, to an open-mouthed appearance. The lips were thick, with downturned upper lip and lower lip that was shorter than the upper lip. Most patients had a narrow, high-arched palate with full or submucous cleft and dysphonic speech. Large and protruding incisors were seen in younger patients. All patients had narrow, elongated necks, trunks, and feet. In some infants, mild joint contractures of the hips, elbows, phalanx, and feet were present and became prominent with age. Most patients had a pilonidal dimple or sinus. X-ray evaluation was normal. Muscle biopsies in 2 patients were compatible with spinal muscular atrophy, with normal molecular SMA tests. Mitochondria appeared normal on electron microscopy examination, and there was normal activity of the mitochondrial respiratory chain enzymes in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678320" 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="Graham, J. M., Jr., Zadeh, N., Kelley, M., Tan, E. S., Liew, W., Tan, V., Deardorff, M. A., Wilson, G. N., Sagi-Dain, L., Shalev, S. A. <strong>KCNK9 imprinting syndrome--further delineation of a possible treatable disorder.</strong> Am. J. Med. Genet. 170A: 2632-2637, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27151206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27151206</a>] [<a href="https://doi.org/10.1002/ajmg.a.37740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27151206">Graham et al. (2016)</a> described 4 unrelated patients, aged 18 months to 3 years, with Birk-Barel syndrome. All had congenital hypotonia, developmental delay, feeding difficulties, restricted facial movements, and variable dysmorphic features, including dolichocephaly with bitemporal narrowing, short philtrum, tented upper lip, palatal abnormalities, and small mandible. Three of the patients tested had normal brain imaging. Two of the children were being treated with the nonsteroidal antiinflammatory drug mefenamic acid (MFA), one child for 6 months and the other for 1 year, with some improvement in development and responsiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27151206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Sediva, M., Lassuthova, P., Zamecnik, J., Sedlackova, L., Seeman, P., Haberlova, J. <strong>Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.</strong> Europ. J. Med. Genet. 63: 103619, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30690205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30690205</a>] [<a href="https://doi.org/10.1016/j.ejmg.2019.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30690205">Sediva et al. (2020)</a> described a 17-year-old girl who had hypotonia, cleft palate, micrognathia, a tented upper lip, short philtrum, and low-set ears at birth. At 11 months of age, she was found to have psychomotor delay, hypotonia with areflexia, and mild contractures of the biceps and triceps. EMG showed signs of an axonal motor peripheral neuropathy. Muscle biopsy at 18 months of age showed neurogenic transformation with mosaic atrophy of type 2 fibers and hypertrophy of type 1 fibers. Brain MRI at 11 years of age was normal. In adolescence she was found to have borderline impaired intellectual development. Examination at 17 years of age showed tongue fasciculations, lagophthalmos, dysarthria, dysphonia, and dysphagia. She had features of a mild cerebellar syndrome and areflexia with generalized mild muscle weakness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30690205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Cousin, M. A., Veale, E. L., Dsouza, N. R., Tripathi, S., Holden, R. G., Arelin, M., Beek, G., Bekheirnia, M. R., Beygo, J., Bhambhani, V., Bialer, M., Bigoni, S., and 59 others. <strong>Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.</strong> Genome Med. 14: 62, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35698242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35698242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35698242[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/10.1186/s13073-022-01064-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35698242">Cousin et al. (2022)</a> described clinical features in 47 patients from 29 families with BIBARS, including 26 newly reported patients from 22 families. The predominant features included motor and speech delay, mildly to profoundly impaired intellectual development, feeding difficulties, hypotonia, and behavioral issues such as aggression, autism spectrum disorder, and hyperactivity. Additional features in some patients included seizures, sleep apnea, and scoliosis. Dysmorphic features in the patient cohort included elongated face, thin upper lip, microretrognathia, bitemporal narrowing, and highly arched eyebrows. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35698242" 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="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a> performed linkage analysis of 7 affected individuals, 1 healthy individual, and 4 obligatory-transmitting mothers with 400 polymorphic markers. Assuming the disease was caused by mutation in a maternally imprinted gene, <a href="#1" class="mim-tip-reference" title="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a> looked for a genomic locus with a haplotype shared by the obligatory transmitting healthy mothers and their affected children, but not their healthy children. They identified a single locus spanning 37.9 cm on chromosome 8q24, between marker D8S514 and the telomeric end of 8q. Further linkage analysis narrowed the interval. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678320" 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>Within the interval on 8q24 linked to a mental retardation dysmorphism syndrome, <a href="#1" class="mim-tip-reference" title="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a> identified only one imprinted gene: KCNK9 (<a href="/entry/605874">605874</a>), which undergoes paternal silencing in humans and mice and is exclusively expressed from the maternal allele in the brain. <a href="#1" class="mim-tip-reference" title="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a> identified a missense mutation in exon 2 of the maternal copy of KCNK9, a gly236-to-arg substitution (G236R; <a href="/entry/605874#0001">605874.0001</a>). Identification of this mutation in all affected family members and their obligatory carrier mothers implied dominant inheritance with paternal imprinting. The mutation was not found in any of 548 chromosomes from ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By exome sequencing in 4 unrelated children with developmental delay and central hypotonia, <a href="#3" class="mim-tip-reference" title="Graham, J. M., Jr., Zadeh, N., Kelley, M., Tan, E. S., Liew, W., Tan, V., Deardorff, M. A., Wilson, G. N., Sagi-Dain, L., Shalev, S. A. <strong>KCNK9 imprinting syndrome--further delineation of a possible treatable disorder.</strong> Am. J. Med. Genet. 170A: 2632-2637, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27151206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27151206</a>] [<a href="https://doi.org/10.1002/ajmg.a.37740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27151206">Graham et al. (2016)</a> identified de novo heterozygosity for the KCNK9 G236R mutation previously identified by <a href="#1" class="mim-tip-reference" title="Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S. <strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong> Am. J. Hum. Genet. 83: 193-199, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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/10.1016/j.ajhg.2008.07.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678320">Barel et al. (2008)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27151206+18678320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Sediva, M., Lassuthova, P., Zamecnik, J., Sedlackova, L., Seeman, P., Haberlova, J. <strong>Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.</strong> Europ. J. Med. Genet. 63: 103619, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30690205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30690205</a>] [<a href="https://doi.org/10.1016/j.ejmg.2019.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30690205">Sediva et al. (2020)</a> identified a heterozygous mutation in the KCNK9 gene (A237D; <a href="/entry/605874#0002">605874.0002</a>) in a 17-year-old girl with Birk-Barel syndrome. The mutation was identified by whole-exome sequencing. The patient's father and maternal grandparents did not have the mutation; her mother was not available for testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30690205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Cousin, M. A., Veale, E. L., Dsouza, N. R., Tripathi, S., Holden, R. G., Arelin, M., Beek, G., Bekheirnia, M. R., Beygo, J., Bhambhani, V., Bialer, M., Bigoni, S., and 59 others. <strong>Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.</strong> Genome Med. 14: 62, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35698242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35698242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35698242[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/10.1186/s13073-022-01064-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35698242">Cousin et al. (2022)</a> reported the molecular features in 47 patients from 29 families with BIBARS, including 26 newly identified patients from 22 families. All of the patients had heterozygous mutations in the KCNK9 gene, which were identified by gene panel testing, whole-exome sequencing, or whole-genome sequencing. Fifteen of the mutations were novel, and 2 mutation hotspots were identified, at Gly236 and Arg131. Analysis of the molecular pathology of these mutations by computational modeling, simulations of molecular dynamics, and patch-clamp electrophysiology studies demonstrated that the majority of the mutations altered KCNK9 channel function. Interestingly, some of the mutations, such as G236R (<a href="/entry/605874#0001">605874.0001</a>), resulted in reduced inwardly rectifying currents whereas other mutations resulted in significantly increased outward currents; both mechanisms, however, resulted in the same clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35698242" 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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Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S.
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<strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong>
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Am. J. Hum. Genet. 83: 193-199, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18678320[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=18678320" 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/j.ajhg.2008.07.010" target="_blank">Full Text</a>]
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Cousin, M. A., Veale, E. L., Dsouza, N. R., Tripathi, S., Holden, R. G., Arelin, M., Beek, G., Bekheirnia, M. R., Beygo, J., Bhambhani, V., Bialer, M., Bigoni, S., and 59 others.
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<strong>Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.</strong>
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Genome Med. 14: 62, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35698242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35698242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35698242[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=35698242" 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/10.1186/s13073-022-01064-4" target="_blank">Full Text</a>]
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Graham, J. M., Jr., Zadeh, N., Kelley, M., Tan, E. S., Liew, W., Tan, V., Deardorff, M. A., Wilson, G. N., Sagi-Dain, L., Shalev, S. A.
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<strong>KCNK9 imprinting syndrome--further delineation of a possible treatable disorder.</strong>
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Am. J. Med. Genet. 170A: 2632-2637, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27151206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27151206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27151206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37740" target="_blank">Full Text</a>]
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Sediva, M., Lassuthova, P., Zamecnik, J., Sedlackova, L., Seeman, P., Haberlova, J.
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<strong>Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.</strong>
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Europ. J. Med. Genet. 63: 103619, 2020. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30690205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30690205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30690205" 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/j.ejmg.2019.01.009" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 01/25/2023
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Hilary J. Vernon - updated : 11/25/2020<br>Carol A. Bocchini - updated : 07/31/2018
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Ada Hamosh : 9/16/2008
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carol : 11/30/2020<br>carol : 11/25/2020<br>carol : 07/31/2018<br>alopez : 09/19/2008<br>alopez : 9/19/2008<br>alopez : 9/16/2008
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BIRK-BAREL MENTAL RETARDATION DYSMORPHISM SYNDROME<br />
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<strong>SNOMEDCT:</strong> 764861005;
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<strong>ORPHA:</strong> 166108;
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Birk-Barel syndrome
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KCNK9
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<p>A number sign (#) is used with this entry because of evidence that Birk-Barel syndrome (BIBARS) is caused by heterozygous mutation in the KCNK9 gene (605874) on chromosome 8q24.</p>
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<strong>Description</strong>
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<p>Birk-Barel syndrome (BIBARS) is a paternally imprinted, autosomal dominant disorder characterized by motor and speech delay, impaired intellectual development, early feeding difficulties, muscular hypotonia, and behavioral abnormalities, including hyperactivity and aggression (summary by Cousin et al., 2022). </p>
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<p>Barel et al. (2008) reported an Israeli-Arab kindred with an apparently maternally transmitted (imprinted with paternal silencing) syndrome of mental retardation, hypotonia, and characteristic dysmorphism. All affected individuals had moderate to severe mental retardation and were hyperactive. Severe feeding difficulties at infancy, requiring tube feeding in most, were followed in all patients by dysphagia of solid foods until near puberty. Generalized hypotonia at an early age was followed by weakness of proximal muscles and of the supra- and infrascapular and trapezius muscles. Coordination, tendon reflexes, deep and superficial sensation, and vibration were all normal. Babinski sign was negative. Hearing, vision, and ophthalmologic examination were normal. All affected individuals had similar dysmorphic features with most elements being more prominent at younger ages. The face was elongated with narrow bitemporal diameter, mild atrophy of temporalis and masseter muscles, and reduced facial movements. The eyebrows were flared, bushy, and arched upward, and downturned eyelids and congested conjunctivae were present in most patients. Ears were mildly protruding with a very prominent fold of the crux of the helix and a prominent antihelical fold. The nasal bridge was high and narrow with a broad nasal tip. The columella was normal, but the philtrum was extremely short, broad, and thick in all patients. The maxillary and premaxillary regions were prominent with hypotonia of the mandible and micrognathia, leading, in combination with the short philtrum, to an open-mouthed appearance. The lips were thick, with downturned upper lip and lower lip that was shorter than the upper lip. Most patients had a narrow, high-arched palate with full or submucous cleft and dysphonic speech. Large and protruding incisors were seen in younger patients. All patients had narrow, elongated necks, trunks, and feet. In some infants, mild joint contractures of the hips, elbows, phalanx, and feet were present and became prominent with age. Most patients had a pilonidal dimple or sinus. X-ray evaluation was normal. Muscle biopsies in 2 patients were compatible with spinal muscular atrophy, with normal molecular SMA tests. Mitochondria appeared normal on electron microscopy examination, and there was normal activity of the mitochondrial respiratory chain enzymes in muscle. </p><p>Graham et al. (2016) described 4 unrelated patients, aged 18 months to 3 years, with Birk-Barel syndrome. All had congenital hypotonia, developmental delay, feeding difficulties, restricted facial movements, and variable dysmorphic features, including dolichocephaly with bitemporal narrowing, short philtrum, tented upper lip, palatal abnormalities, and small mandible. Three of the patients tested had normal brain imaging. Two of the children were being treated with the nonsteroidal antiinflammatory drug mefenamic acid (MFA), one child for 6 months and the other for 1 year, with some improvement in development and responsiveness. </p><p>Sediva et al. (2020) described a 17-year-old girl who had hypotonia, cleft palate, micrognathia, a tented upper lip, short philtrum, and low-set ears at birth. At 11 months of age, she was found to have psychomotor delay, hypotonia with areflexia, and mild contractures of the biceps and triceps. EMG showed signs of an axonal motor peripheral neuropathy. Muscle biopsy at 18 months of age showed neurogenic transformation with mosaic atrophy of type 2 fibers and hypertrophy of type 1 fibers. Brain MRI at 11 years of age was normal. In adolescence she was found to have borderline impaired intellectual development. Examination at 17 years of age showed tongue fasciculations, lagophthalmos, dysarthria, dysphonia, and dysphagia. She had features of a mild cerebellar syndrome and areflexia with generalized mild muscle weakness. </p><p>Cousin et al. (2022) described clinical features in 47 patients from 29 families with BIBARS, including 26 newly reported patients from 22 families. The predominant features included motor and speech delay, mildly to profoundly impaired intellectual development, feeding difficulties, hypotonia, and behavioral issues such as aggression, autism spectrum disorder, and hyperactivity. Additional features in some patients included seizures, sleep apnea, and scoliosis. Dysmorphic features in the patient cohort included elongated face, thin upper lip, microretrognathia, bitemporal narrowing, and highly arched eyebrows. </p>
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<strong>Mapping</strong>
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<p>Barel et al. (2008) performed linkage analysis of 7 affected individuals, 1 healthy individual, and 4 obligatory-transmitting mothers with 400 polymorphic markers. Assuming the disease was caused by mutation in a maternally imprinted gene, Barel et al. (2008) looked for a genomic locus with a haplotype shared by the obligatory transmitting healthy mothers and their affected children, but not their healthy children. They identified a single locus spanning 37.9 cm on chromosome 8q24, between marker D8S514 and the telomeric end of 8q. Further linkage analysis narrowed the interval. </p>
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<strong>Molecular Genetics</strong>
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<p>Within the interval on 8q24 linked to a mental retardation dysmorphism syndrome, Barel et al. (2008) identified only one imprinted gene: KCNK9 (605874), which undergoes paternal silencing in humans and mice and is exclusively expressed from the maternal allele in the brain. Barel et al. (2008) identified a missense mutation in exon 2 of the maternal copy of KCNK9, a gly236-to-arg substitution (G236R; 605874.0001). Identification of this mutation in all affected family members and their obligatory carrier mothers implied dominant inheritance with paternal imprinting. The mutation was not found in any of 548 chromosomes from ethnically matched controls. </p><p>By exome sequencing in 4 unrelated children with developmental delay and central hypotonia, Graham et al. (2016) identified de novo heterozygosity for the KCNK9 G236R mutation previously identified by Barel et al. (2008). </p><p>Sediva et al. (2020) identified a heterozygous mutation in the KCNK9 gene (A237D; 605874.0002) in a 17-year-old girl with Birk-Barel syndrome. The mutation was identified by whole-exome sequencing. The patient's father and maternal grandparents did not have the mutation; her mother was not available for testing. </p><p>Cousin et al. (2022) reported the molecular features in 47 patients from 29 families with BIBARS, including 26 newly identified patients from 22 families. All of the patients had heterozygous mutations in the KCNK9 gene, which were identified by gene panel testing, whole-exome sequencing, or whole-genome sequencing. Fifteen of the mutations were novel, and 2 mutation hotspots were identified, at Gly236 and Arg131. Analysis of the molecular pathology of these mutations by computational modeling, simulations of molecular dynamics, and patch-clamp electrophysiology studies demonstrated that the majority of the mutations altered KCNK9 channel function. Interestingly, some of the mutations, such as G236R (605874.0001), resulted in reduced inwardly rectifying currents whereas other mutations resulted in significantly increased outward currents; both mechanisms, however, resulted in the same clinical phenotype. </p>
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<strong>REFERENCES</strong>
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Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., Birk, O. S.
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<strong>Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.</strong>
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Am. J. Hum. Genet. 83: 193-199, 2008.
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[PubMed: 18678320]
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[Full Text: https://doi.org/10.1016/j.ajhg.2008.07.010]
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Cousin, M. A., Veale, E. L., Dsouza, N. R., Tripathi, S., Holden, R. G., Arelin, M., Beek, G., Bekheirnia, M. R., Beygo, J., Bhambhani, V., Bialer, M., Bigoni, S., and 59 others.
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<strong>Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.</strong>
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Genome Med. 14: 62, 2022.
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[PubMed: 35698242]
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[Full Text: https://doi.org/10.1186/s13073-022-01064-4]
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Graham, J. M., Jr., Zadeh, N., Kelley, M., Tan, E. S., Liew, W., Tan, V., Deardorff, M. A., Wilson, G. N., Sagi-Dain, L., Shalev, S. A.
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<strong>KCNK9 imprinting syndrome--further delineation of a possible treatable disorder.</strong>
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Am. J. Med. Genet. 170A: 2632-2637, 2016.
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[PubMed: 27151206]
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[Full Text: https://doi.org/10.1002/ajmg.a.37740]
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Sediva, M., Lassuthova, P., Zamecnik, J., Sedlackova, L., Seeman, P., Haberlova, J.
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<strong>Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.</strong>
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Europ. J. Med. Genet. 63: 103619, 2020. Note: Electronic Article.
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[PubMed: 30690205]
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[Full Text: https://doi.org/10.1016/j.ejmg.2019.01.009]
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Hilary J. Vernon - updated : 01/25/2023<br>Hilary J. Vernon - updated : 11/25/2020<br>Carol A. Bocchini - updated : 07/31/2018
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carol : 01/25/2023<br>carol : 11/30/2020<br>carol : 11/25/2020<br>carol : 07/31/2018<br>alopez : 09/19/2008<br>alopez : 9/19/2008<br>alopez : 9/16/2008
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