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Entry
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- #251260 - NIJMEGEN BREAKAGE SYNDROME; NBS
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- OMIM
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<p>
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<span class="h4">#251260</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/251260"><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="#clinicalManagement">Clinical Management</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#mapping">Mapping</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population 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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</a>
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</h4>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" 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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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=NIJMEGEN BREAKAGE 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=2823&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/NBK1176/" 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://medlineplus.gov/genetics/condition/nijmegen-breakage-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=251260[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=647" 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/740a7369-681d-4684-ae13-597fe36828d7/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 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:7400" 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/251260" 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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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</a>
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</span>
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<div id="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:251260" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 234638009<br />
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<strong>ORPHA:</strong> 647<br />
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<strong>DO:</strong> 7400<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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251260
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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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NIJMEGEN BREAKAGE SYNDROME; NBS
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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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ATAXIA-TELANGIECTASIA VARIANT V1; AT-V1<br />
|
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MICROCEPHALY WITH NORMAL INTELLIGENCE, IMMUNODEFICIENCY, AND LYMPHORETICULAR MALIGNANCIES<br />
|
|
SEEMANOVA SYNDROME II<br />
|
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NONSYNDROMAL MICROCEPHALY, AUTOSOMAL RECESSIVE, WITH NORMAL INTELLIGENCE<br />
|
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IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY
|
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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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<a id="includedTitles" 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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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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BERLIN BREAKAGE SYNDROME, INCLUDED; BBS, INCLUDED
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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ATAXIA-TELANGIECTASIA VARIANT V2, INCLUDED; AT-V2, INCLUDED
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</span>
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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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</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">
|
|
<a href="/geneMap/8/392?start=-3&limit=10&highlight=392">
|
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8q21.3
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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">
|
|
Nijmegen breakage syndrome
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/251260"> 251260 </a>
|
|
</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">
|
|
NBN
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602667"> 602667 </a>
|
|
</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 ">
|
|
<a href="/clinicalSynopsis/251260" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<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')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
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|
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|
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|
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|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/251260" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/251260" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- 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 />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Height </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Short stature, most below 3rd percentile for height <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855060&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855060</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Prenatal growth retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22033007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22033007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/764.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.90</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/764.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015934&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015934</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Mastoiditis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52404001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52404001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H70.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H70.90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H70.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H70.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/383.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">383.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024904&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024904</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000265</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000265</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sloping forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857679&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857679</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000340" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000340</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000340" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000340</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=55cd7ed83868b07da866b39707988156" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Forehead,Sloping-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=55cd7ed83868b07da866b39707988156" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Prominent midface <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858732&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858732</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010620" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010620</a>]</span><br /> -
|
|
Upward slanting of palpebral fissures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246799009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246799009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423109</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000582" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000582</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000582" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000582</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ears </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Large dysplastic ears <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855062&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855062</a>]</span><br /> -
|
|
Otitis media <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65363002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65363002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H66.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H66.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H66.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H66.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/382.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">382.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000388</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000388</a>]</span><br />
|
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|
</span>
|
|
</div>
|
|
</div>
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Choanal atresia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204508009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204508009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q30.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q30.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/748.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">748.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008297&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008297</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000453" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000453</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000453" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000453</a>]</span><br /> -
|
|
Long nose (beaked or upturned) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855063</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003189" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003189</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=d37d499826d234a337ac0bfdfdb7751a" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nose,Long-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=d37d499826d234a337ac0bfdfdb7751a" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
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|
</span>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cleft lip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80281008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80281008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008924</a>, <a href="https://bioportal.bioontology.org/search?q=C4321245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4321245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000204" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000204</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span><br /> -
|
|
Cleft palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nasopharynx </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sinusitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36971009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36971009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J32" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J32</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037199&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037199</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000246" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000246</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000246" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000246</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Airways </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Bronchitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/10509002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">10509002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35301006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35301006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32398004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32398004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/J40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/J20.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J20.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">490</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/466.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">466.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149514</a>, <a href="https://bioportal.bioontology.org/search?q=C0006277&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006277</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012388</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0012387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012387</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012387</a>]</span><br /> -
|
|
Bronchiectasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12295008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12295008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J47" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J47</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/J47.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J47.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/494" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">494</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006267&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006267</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002110" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002110</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002110" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002110</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Lung </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Recurrent pneumonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/699014000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">699014000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0694550&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0694550</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006532" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006532</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006532" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006532</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Diarrhea and recurrent GI infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855061&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855061</a>]</span><br /> -
|
|
Anal stenosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/69914001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">69914001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0262374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0262374</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002025</a>]</span><br /> -
|
|
Anal atresia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204712000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204712000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q42.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q42.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002023</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002023</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
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|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Kidneys </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hydronephrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43064006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43064006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N13.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N13.30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/591" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">591</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020295&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020295</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000126</a>]</span><br /> -
|
|
Recurrent urinary tract infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197927001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197927001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/473116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">473116008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0262655&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0262655</a>, <a href="https://bioportal.bioontology.org/search?q=C3532611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3532611</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000010</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000010</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
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|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cafe au lait spots <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/201281002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">201281002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L81.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L81.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221263&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221263</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000957</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000957</a>]</span><br /> -
|
|
Depigmented spots <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806427</a>]</span><br /> -
|
|
Progressive vitiligo <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806428</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005602</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005602</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<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">
|
|
|
|
- Normal IQ in infancy, then IQ drops with age <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855058&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855058</a>]</span><br /> -
|
|
Mental retardation by the age of 7 years <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855059&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855059</a>]</span><br /> -
|
|
Hyperactivity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44548000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44548000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424295&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424295</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000752" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000752</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000752" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000752</a>]</span><br /> -
|
|
Neurodegeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027746&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027746</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Primary ovarian failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65846009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65846009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237788002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237788002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E28.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E28.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085215&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085215</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autoimmune hemolytic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413603009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413603009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/283.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">283.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002880&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002880</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001890" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001890</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001890" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001890</a>]</span><br /> -
|
|
Thrombocytopenia post hemolytic anemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855069&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855069</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Dysgammaglobulinemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123782009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123782009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013374</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002961" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002961</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002961" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002961</a>]</span><br /> -
|
|
Mild to moderately reduced T cell count <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855064&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855064</a>]</span><br /> -
|
|
Relatively increased number of natural killer cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855065&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855065</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
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- Lymphoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1163043007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1163043007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/188676008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">188676008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/118600007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">118600007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C85.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C85.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024299&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024299</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002665" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002665</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002665" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002665</a>]</span><br /> -
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Glioma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/115240006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">115240006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/393564001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">393564001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017638&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017638</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009733</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009733</a>]</span><br /> -
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Medulloblastoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156923005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156923005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/443333004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">443333004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025149&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025149</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002885" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002885</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002885" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002885</a>]</span><br /> -
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Rhabdomyosarcoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30924005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30924005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302847003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302847003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035412&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035412</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002859" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002859</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002859" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002859</a>]</span><br />
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<strong> LABORATORY ABNORMALITIES </strong>
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<div style="margin-left: 2em;">
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- Normal alpha fetoprotein <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166558007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166558007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0428522&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0428522</a>]</span><br /> -
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Low T cell count <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2931322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2931322</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005403</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005403</a>]</span><br /> -
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Low B cell count <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855067&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855067</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010976" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010976</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010976" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010976</a>]</span><br /> -
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Low CD4+ count <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855068&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855068</a>]</span><br /> -
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Low CD4+/CD8+ ratio <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853905&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853905</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033222" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033222</a>]</span><br />
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</span>
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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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<span class="mim-font">
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- Premature death <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855073&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855073</a>]</span><br /> -
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Spontaneous chromosomal instability with multiple rearrangements, especially chromosome 7 and 14<br /> -
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Chromosomal hypersensitivity to ionizing radiation and alkylating agents<br /> -
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Radioresistant DNA synthesis<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 mutations in the Nijmegen breakage syndrome gene (NBS1, <a href="/entry/602667#0001">602667.0001</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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<div>
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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 Nijmegen breakage syndrome (NBS) is caused by homozygous or compound heterozygous mutation in the NBS1 gene (NBN; <a href="/entry/602667">602667</a>) on chromosome 8q21.</p>
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<a id="description" class="mim-anchor"></a>
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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<p>The Nijmegen breakage syndrome (NBS) and the phenotypically indistinguishable Berlin breakage syndrome (BBS) are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. Cells from NBS/BBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia (AT; <a href="/entry/208900">208900</a>), but NBS/BBS patients have a distinct clinical phenotype.</p><p>The clinical features of LIG4 syndrome (<a href="/entry/606593">606593</a>), caused by mutation in the LIG4 gene (<a href="/entry/601837">601837</a>), resemble those of NBS.</p>
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<strong>Clinical Features</strong>
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<span class="mim-text-font">
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<p>Patients with AT variant-1 are clinically indistinguishable from those with AT variant-2. These patients share mitogenic features with AT, such as spontaneous chromosomal instability, clonal occurrence of rearrangements involving, in particular, chromosomes 7 and 14, chromosomal and cellular hypersensitivity to irradiation, and radioresistant DNA synthesis. However, patients with AT-V have neither ataxia nor telangiectasia, and are characterized by pronounced microcephaly, microgenia, 'bird-like' facies, immunodeficiency, and normal serum levels of alpha-fetoprotein. V1 and V2 are distinguished from one another only by complementation analysis (<a href="#31" class="mim-tip-reference" title="Wegner, R.-D., Metzger, M., Hanefeld, F., Jaspers, N. G. J., Baan, C., Magdorf, K., Kunze, J., Sperling, K. <strong>A new chromosomal instability disorder confirmed by complementation studies.</strong> Clin. Genet. 33: 20-32, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3277755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3277755</a>]" pmid="3277755">Wegner et al., 1988</a>; <a href="#16" class="mim-tip-reference" title="Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K. <strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong> Am. J. Hum. Genet. 60: 605-610, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042920</a>]" pmid="9042920">Saar et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3277755+9042920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C., van Munster, P. J. J., Bakkeren, J. A. J. M., Taalman, R. D. F. M. <strong>A new chromosomal instability disorder: the Nijmegen breakage syndrome.</strong> Acta Paediat. Scand. 70: 557-564, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7315300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7315300</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1981.tb05740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7315300">Weemaes et al. (1981)</a> described 2 sons of second-cousin parents who had microcephaly, stunted growth, mental retardation, cafe-au-lait spots, and immunodeficiency. Cytogenetic studies showed a typical form of chromosome instability with multiple rearrangements of chromosomes 7 and 14. A lower frequency of the same chromosome abnormalities was found in the father and 3 of the phenotypically normal sibs. <a href="#17" class="mim-tip-reference" title="Seemanova, E., Passarge, E., Beneskova, D., Houstek, J., Kasal, P., Sevcikova, M. <strong>Familial microcephaly with normal intelligence, immunodeficiency, and risk of lymphoreticular malignancies: a new autosomal recessive disorder.</strong> Am. J. Med. Genet. 20: 639-648, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3857858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3857858</a>] [<a href="https://doi.org/10.1002/ajmg.1320200410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3857858">Seemanova et al. (1985)</a> described 9 patients in 6 families with a 'new' disorder characterized by low birth weight for dates, microcephaly with normal intelligence, receding mandibula, cellular and humoral immune defects, and increased risk of lymphoreticular malignancies. No evidence of chromosomal instability was found, but chromosome analysis was difficult because the rate of blastic transformation with phytohemagglutinin was low. Even sex ratio, consanguinity in 1 family and grandparental isonymy in a second, and the occurrence of 2 affected sibs in 3 families supported autosomal recessive inheritance. Bronchiectasis, pneumonia, otitis media, mastoiditis, and sinusitis occurred. Immunoglobulin levels were reduced. In 2 sibs, acute lymphoblastic leukemia developed at ages 9 years and 12 months, respectively. Generalized malignancies, apparently originating in the mediastinum and variously identified as malignant lymphogranuloma, acute undifferentiated hemoblastoma and mediastinal blastoma (probably neuroblastoma) was the cause of death in several. The oldest surviving patient of 4 was 12.5 years old. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7315300+3857858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W. <strong>A chromosome breakage syndrome with profound immunodeficiency.</strong> Blood 67: 1251-1256, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2421804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2421804</a>]" pmid="2421804">Conley et al. (1986)</a> described a 21-year-old woman with growth failure, immunodeficiency, and chromosomal breakage syndrome involving chromosomes 7 and 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2421804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Maraschio, P., Peretti, D., Lambiase, S., Lo Curto, F., Caufin, D., Gargantini, L., Minoli, L., Zuffardi, O. <strong>A new chromosome instability disorder.</strong> Clin. Genet. 30: 353-365, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3802554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3802554</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1986.tb01892.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3802554">Maraschio et al. (1986)</a> described the case of a 31-year-old woman with primary amenorrhea, microcephaly and immunodeficiency. Her healthy parents were related as first cousins once removed. A younger sister, who also had primary amenorrhea, had died at age 20 years with a malignant lymphoma. Chromosome studies revealed a high proportion of metaphases with multiple chromosome aberrations. The same unbalanced translocation, t(8q;21q), was present in about 59% of metaphases. A few rearrangements involving chromosomes 7 and 14, similar to those described in patients with ataxia-telangiectasia, were found. Sister chromatid exchanges were not increased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3802554" 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="#24" class="mim-tip-reference" title="Teebi, A. S., Al-Awadi, S. A., White, A. G. <strong>Autosomal recessive nonsyndromal microcephaly with normal intelligence.</strong> Am. J. Med. Genet. 26: 355-359, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812587</a>] [<a href="https://doi.org/10.1002/ajmg.1320260214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3812587">Teebi et al. (1987)</a> reported a large inbred Arab kindred in which 8 individuals in 5 sibships had microcephaly and normal intelligence. Two died of acute lymphoreticular malignancy or bronchial pneumonia. Immunologic and chromosomal studies carried out in 3 affected living sibs yielded normal results. <a href="#22" class="mim-tip-reference" title="Taalman, R. D. F. M., Hustinx, T. W. J., Weemaes, C. M. R., Seemanova, E., Schmidt, A., Passarge, E., Scheres, J. M. J. C. <strong>Further delineation of the Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 32: 425-431, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786340</a>] [<a href="https://doi.org/10.1002/ajmg.1320320332" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2786340">Taalman et al. (1989)</a> reported the findings in 5 families, 2 from the Netherlands and 3 from Czechoslovakia, containing a total of 8 patients with NBS. The patients had microcephaly, short stature, a 'bird-like' face, and immunologic defects. The basic karyotype in these patients was normal, but in a fifth or more of metaphases, rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all 5 living patients were very sensitive to ionizing radiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2786340+3812587" 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="Chrzanowska, K. H., Kleijer, W. J., Krajewska-Walasek, M., Bialecka, M., Gutkowska, A., Goryluk-Kozakiewicz, B., Michalkiewicz, J., Stachowski, J., Gregorek, H., Lyson-Wojciechowska, G., Janowicz, W., Jozwiak, S. <strong>Eleven Polish patients with microcephaly, immunodeficiency and chromosomal instability: the Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 57: 462-471, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545870</a>] [<a href="https://doi.org/10.1002/ajmg.1320570321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545870">Chrzanowska et al. (1995)</a> reported 11 patients with Nijmegen breakage syndrome from 8 independent Polish families, with a total of 3 pairs of affected sibs. The clinical pattern included microcephaly, particular 'bird-like' face, growth retardation, and, in some cases, mild to moderate mental deficiency. Most of the patients had recurrent respiratory tract infections. One girl developed B-cell lymphoma. Chromosome studies showed structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14, in a proportion of metaphase in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were studied from this point of view. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The clinical, immunologic, chromosomal, and cell-biologic findings in 42 patients in the NBS Registry in Nijmegen were reviewed by <a href="#27" class="mim-tip-reference" title="van der Burgt, I., Chrzanowska, K. H., Smeets, D., Weemaes, C. <strong>Nijmegen breakage syndrome.</strong> J. Med. Genet. 33: 153-156, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929954</a>] [<a href="https://doi.org/10.1136/jmg.33.2.153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8929954">van der Burgt et al. (1996)</a>. Although the immunologic, chromosomal, and cell-biologic findings resembled those in AT, the clinical findings were quite different. The authors stated that NBS appears to be a separate entity that is not allelic to AT, as indicated by the fact that linkage studies exclude 11q22-q23, where the gene for ataxia-telangiectasia is located, as the site of the NBS gene. None of the patients had signs of cerebellar ataxia, apraxic eye movements, or other neurologic abnormalities except for twin girls described by <a href="#6" class="mim-tip-reference" title="Curry, C. J. R., O'Lague, P., Tsai, J., Hutchison, H. T., Jaspers, N. G. J., Wara, D., Gatti, R. A. <strong>AT(Fresno): a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome.</strong> Am. J. Hum. Genet. 45: 270-275, 1989. Note: Erratum: Am. J. Hum. Genet. 45: 663 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2491181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2491181</a>]" pmid="2491181">Curry et al. (1989)</a> who had clinical symptoms of both NBS and AT (see <a href="/entry/607585#0014">607585.0014</a>). Complementation studies assigned these cases to NBS complementation group V1. Subtle scleral telangiectasia was noted in 10 of 25 patients. The patients did not have raised serum AFP levels, as in ataxia-telangiectasia. Twelve patients varying in age from 1 to 22 years had developed lymphoma. One patient developed a glioma at the age of 12 years, 1 patient a medulloblastoma at 15 years, and 1 patient a rhabdomyosarcoma at 4 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8929954+2491181" 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="Der Kaloustian, V. M., Kleijer, W., Booth, A., Auerbach, A. D., Mazer, B., Elliott, A. M., Abish, S., Usher, R., Watters, G., Vekemans, M., Eydoux, P. <strong>Possible new variant of Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 65: 21-26, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8914736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8914736</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1<21::AID-AJMG3>3.0.CO;2-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8914736">Der Kaloustian et al. (1996)</a> described a boy who in addition to typical manifestations had penoscrotal hypospadias. He had lymphopenia with low percentage of B and T cells, absence of IgE, and low response to mitogen stimulation. At the age of 4 years he developed rhabdomyosarcoma. Cytogenetic study showed multiple chromatid and chromosome breaks, structural rearrangements involving mainly chromosomes 7 and 14, and different monosomies in 57 to 58% of cells. Nijmegen breakage syndrome was diagnosed, although hypospadias and a high percentage of monosomic cells led the authors to suggest he represented a specific variant of this syndrome. <a href="#7" class="mim-tip-reference" title="Der Kaloustian, V. M., Kleijer, W., Booth, A., Auerbach, A. D., Mazer, B., Elliott, A. M., Abish, S., Usher, R., Watters, G., Vekemans, M., Eydoux, P. <strong>Possible new variant of Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 65: 21-26, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8914736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8914736</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1<21::AID-AJMG3>3.0.CO;2-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8914736">Der Kaloustian et al. (1996)</a> suggested that the boy described by <a href="#32" class="mim-tip-reference" title="Woods, C. G., Leversha, M., Rogers, J. G. <strong>Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.</strong> J. Med. Genet. 32: 301-305, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643362</a>] [<a href="https://doi.org/10.1136/jmg.32.4.301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7643362">Woods et al. (1995)</a> as a patient with Seckel syndrome might have the same variant of Nijmegen breakage syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7643362+8914736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Meyer, S., Kingston, H., Taylor, A. M. R., Byrd, P. J., Last, J. I. K., Brennan, B. M. D., Trueman, S., Kelsey, A., Taylor, G. M., Eden, O. B. <strong>Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site.</strong> Cancer Genet. Cytogenet. 154: 169-174, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15474156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15474156</a>] [<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15474156">Meyer et al. (2004)</a> described a 7-year-old girl with NBS who was homozygous for the NBS1 698del4 mutation (<a href="/entry/602667#0002">602667.0002</a>). She had been diagnosed with perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from chemotherapy. RMS arising perianally is exceedingly uncommon but had previously been described in 2 cases of NBS (<a href="#7" class="mim-tip-reference" title="Der Kaloustian, V. M., Kleijer, W., Booth, A., Auerbach, A. D., Mazer, B., Elliott, A. M., Abish, S., Usher, R., Watters, G., Vekemans, M., Eydoux, P. <strong>Possible new variant of Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 65: 21-26, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8914736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8914736</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1<21::AID-AJMG3>3.0.CO;2-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8914736">Der Kaloustian et al., 1996</a>; <a href="#25" class="mim-tip-reference" title="Tekin, M., Dogu, F., Tacyildiz, N., Akar, E., Ikinciogullari, A., Ogur, G., Yavuz, G., Babacan, E., Akar, N. <strong>657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.</strong> Clin. Genet. 62: 84-88, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123493</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620112.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123493">Tekin et al., 2002</a>). Thus, association with NBS should be considered when a perianal RMS is encountered. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8914736+12123493+15474156" 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="#26" class="mim-tip-reference" title="Tupler, R., Marseglia, G. L., Stefanini, M., Prosperi, E., Chessa, L., Nardo, T., Marchi, A., Maraschio, P. <strong>A variant of the Nijmegen breakage syndrome with unusual cytogenetic features and intermediate cellular radiosensitivity.</strong> J. Med. Genet. 34: 196-202, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9132489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9132489</a>] [<a href="https://doi.org/10.1136/jmg.34.3.196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9132489">Tupler et al. (1997)</a> provided the first report of an Italian case of Nijmegen breakage syndrome. The proband was an immunodeficient, microcephalic, 11-year-old boy with a 'bird-like' face. He developed a T-cell-rich B-cell lymphoma. Spontaneous chromosomal instability was detected in T- and B-lymphocytes and in fibroblasts; chromosomes 7 and 14 were only sporadically involved in the rearrangements and no clonal abnormality was present. The patient appeared to be sensitive both to ionizing radiation and to bleomycin, although his sensitivity did not reach the level of ataxia-telangiectasia reference cells. Although the clinical evaluation suggested to <a href="#26" class="mim-tip-reference" title="Tupler, R., Marseglia, G. L., Stefanini, M., Prosperi, E., Chessa, L., Nardo, T., Marchi, A., Maraschio, P. <strong>A variant of the Nijmegen breakage syndrome with unusual cytogenetic features and intermediate cellular radiosensitivity.</strong> J. Med. Genet. 34: 196-202, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9132489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9132489</a>] [<a href="https://doi.org/10.1136/jmg.34.3.196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9132489">Tupler et al. (1997)</a> a diagnosis of NBS, differences in the cytogenetic and cell-biologic data suggested that the patient might have an allelic form of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9132489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To evaluate the possibility of carrier detection, <a href="#23" class="mim-tip-reference" title="Tanzarella, C., Antoccia, A., Spadoni, E., di Masi, A., Pecile, V., Demori, E., Varon, R., Marseglia, G. L., Tiepolo, L., Maraschio, P. <strong>Chromosome instability and nibrin protein variants in NBS heterozygotes.</strong> Europ. J. Hum. Genet. 11: 297-303, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12708449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12708449</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12708449">Tanzarella et al. (2003)</a> studied heterozygous individuals from 3 unrelated NBS families with distinct gene deletion mutations for the frequency of spontaneous chromosome abnormalities in blood lymphocytes, x-ray G2 sensitivity in lymphoblastoid cell lines, and the ability to detect nibrin variants by immunoprecipitation and immunoblotting. All 13 heterozygotes showed chromosomal instability (chromatid and chromosomal breaks as well as rearrangements), but 7 of 8 tested were similar to controls in radiosensitivity. Immunoprecipitation of nibrin detected the normal and variant proteins in carriers from all 3 families, but immunoblotting was not as discriminating. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12708449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Complementation Groups</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Jaspers, N. G. J., Taalman, R. D. F. M., Baan, C. <strong>Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia.</strong> Am. J. Hum. Genet. 42: 66-73, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3337113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3337113</a>]" pmid="3337113">Jaspers et al. (1988)</a> studied fibroblast cultures from 6 unrelated patients with immunodeficiency, developmental delay, microcephaly, and chromosomal instability; 1 of the patients had been described by <a href="#30" class="mim-tip-reference" title="Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C., van Munster, P. J. J., Bakkeren, J. A. J. M., Taalman, R. D. F. M. <strong>A new chromosomal instability disorder: the Nijmegen breakage syndrome.</strong> Acta Paediat. Scand. 70: 557-564, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7315300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7315300</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1981.tb05740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7315300">Weemaes et al. (1981)</a>, 1 by <a href="#19" class="mim-tip-reference" title="Sperling, K. <strong>Analisi dell' eterogeneita nell'uomo.</strong> Prospettive Pediat. 49: 53-66, 1983."None>Sperling (1983)</a>, 3 by <a href="#17" class="mim-tip-reference" title="Seemanova, E., Passarge, E., Beneskova, D., Houstek, J., Kasal, P., Sevcikova, M. <strong>Familial microcephaly with normal intelligence, immunodeficiency, and risk of lymphoreticular malignancies: a new autosomal recessive disorder.</strong> Am. J. Med. Genet. 20: 639-648, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3857858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3857858</a>] [<a href="https://doi.org/10.1002/ajmg.1320200410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3857858">Seemanova et al. (1985)</a>, and 1 by <a href="#5" class="mim-tip-reference" title="Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W. <strong>A chromosome breakage syndrome with profound immunodeficiency.</strong> Blood 67: 1251-1256, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2421804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2421804</a>]" pmid="2421804">Conley et al. (1986)</a>. The cells showed radiosensitivity, clonogenic cell survival, and abnormal inhibition of DNA synthesis. Fibroblasts from all cases showed complementation with the 5 complementation groups of AT. Cross-complementation studies within the group indicated the existence of 2 separate complementation groups, designated V1 and V2, that were genetically distinct from AT. The case of <a href="#5" class="mim-tip-reference" title="Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W. <strong>A chromosome breakage syndrome with profound immunodeficiency.</strong> Blood 67: 1251-1256, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2421804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2421804</a>]" pmid="2421804">Conley et al. (1986)</a> and 1 case of <a href="#19" class="mim-tip-reference" title="Sperling, K. <strong>Analisi dell' eterogeneita nell'uomo.</strong> Prospettive Pediat. 49: 53-66, 1983."None>Sperling (1983)</a> showed complementation with the other cases, and were therefore classified as having V2. The patient of <a href="#19" class="mim-tip-reference" title="Sperling, K. <strong>Analisi dell' eterogeneita nell'uomo.</strong> Prospettive Pediat. 49: 53-66, 1983."None>Sperling (1983)</a> was further studied by <a href="#31" class="mim-tip-reference" title="Wegner, R.-D., Metzger, M., Hanefeld, F., Jaspers, N. G. J., Baan, C., Magdorf, K., Kunze, J., Sperling, K. <strong>A new chromosomal instability disorder confirmed by complementation studies.</strong> Clin. Genet. 33: 20-32, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3277755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3277755</a>]" pmid="3277755">Wegner et al. (1988)</a>. <a href="#31" class="mim-tip-reference" title="Wegner, R.-D., Metzger, M., Hanefeld, F., Jaspers, N. G. J., Baan, C., Magdorf, K., Kunze, J., Sperling, K. <strong>A new chromosomal instability disorder confirmed by complementation studies.</strong> Clin. Genet. 33: 20-32, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3277755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3277755</a>]" pmid="3277755">Wegner et al. (1988)</a> reported 2 sibs with a syndrome identical to that in the patient reported by <a href="#5" class="mim-tip-reference" title="Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W. <strong>A chromosome breakage syndrome with profound immunodeficiency.</strong> Blood 67: 1251-1256, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2421804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2421804</a>]" pmid="2421804">Conley et al. (1986)</a>, as shown by complementation studies. These patients had V2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3277755+2421804+7315300+3857858+3337113" 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="Jaspers, N. G. J., Gatti, R. A., Baan, C., Linssen, P. C. M. L., Bootsma, D. <strong>Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients.</strong> Cytogenet. Cell Genet. 49: 259-263, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3248383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3248383</a>] [<a href="https://doi.org/10.1159/000132673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3248383">Jaspers et al. (1988)</a> performed complementation studies on fibroblast strains from 50 patients with either AT or NBS. Using the radioresistant DNA replication characteristic as a marker, they demonstrated 6 different genetic complementation groups, 2 of which, groups V1 and V2, involved patients with NBS. An individual with clinical symptoms of both AT and NBS was found in group V2, indicating that the 2 disorders are closely related. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3248383" 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 the treatment of malignancies in patients with NBS, <a href="#27" class="mim-tip-reference" title="van der Burgt, I., Chrzanowska, K. H., Smeets, D., Weemaes, C. <strong>Nijmegen breakage syndrome.</strong> J. Med. Genet. 33: 153-156, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929954</a>] [<a href="https://doi.org/10.1136/jmg.33.2.153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8929954">van der Burgt et al. (1996)</a> stated that cytostatics are the first choice; however, radiomimetics (for example, bleomycin) should be avoided, and the chemotherapy doses should be reduced. Radiation therapy should be avoided, since x-irradiation can induce malignancies in NBS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8929954" 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="#10" class="mim-tip-reference" title="Kleier, S., Herrmann, M., Wittwer, B., Varon, R., Reis, A., Horst, J. <strong>Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome.</strong> Clin. Genet. 57: 384-387, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10852373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10852373</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2000.570509.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10852373">Kleier et al. (2000)</a> pointed out that rearrangements involving chromosomes 7 and 14 occur in both ataxia-telangiectasia and NBS. However, NBS patients show characteristic microcephaly, which is rare in ataxia-telangiectasia, and they do not develop ataxia and telangiectasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10852373" 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 6 of the affected Polish families reported by <a href="#4" class="mim-tip-reference" title="Chrzanowska, K. H., Kleijer, W. J., Krajewska-Walasek, M., Bialecka, M., Gutkowska, A., Goryluk-Kozakiewicz, B., Michalkiewicz, J., Stachowski, J., Gregorek, H., Lyson-Wojciechowska, G., Janowicz, W., Jozwiak, S. <strong>Eleven Polish patients with microcephaly, immunodeficiency and chromosomal instability: the Nijmegen breakage syndrome.</strong> Am. J. Med. Genet. 57: 462-471, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545870</a>] [<a href="https://doi.org/10.1002/ajmg.1320570321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545870">Chrzanowska et al. (1995)</a>, <a href="#20" class="mim-tip-reference" title="Stumm, M., Gatti, R. A., Reis, A., Udar, N., Chrzanowska, K., Seemanova, E., Sperling, K., Wegner, R.-D. <strong>The ataxia-telangiectasia-variant genes 1 and 2 are distinct from the ataxia-telangiectasia gene on chromosome 11q23.1. (Letter)</strong> Am. J. Hum. Genet. 57: 960-962, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573059</a>]" pmid="7573059">Stumm et al. (1995)</a> performed haplotype studies and sib-pair analysis and demonstrated lack of linkage to the 11q22-q23 region where the AT locus maps. One of these families had been assigned to complementation group AT-V1 and a second to complementation group AT-V2 by cell-fusion studies. No complementation studies had been done in the other 4 families. <a href="#11" class="mim-tip-reference" title="Komatsu, K., Matsuura, S., Tauchi, H., Endo, S., Kodama, S., Smeets, D., Weemaes, C., Oshimura, M. <strong>The gene for Nijmegen breakage syndrome (V2) is not located on chromosome 11. (Letter)</strong> Am. J. Hum. Genet. 58: 885-888, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644753</a>]" pmid="8644753">Komatsu et al. (1996)</a> likewise excluded the ATM locus on chromosome 11 as the site of the mutation in AT-V2. They found that the sensitivity of V2 cells to radiation is unchanged after the transfer of an extra copy of a normal chromosome 11 into the cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8644753+7545870+7573059" 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="#16" class="mim-tip-reference" title="Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K. <strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong> Am. J. Hum. Genet. 60: 605-610, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042920</a>]" pmid="9042920">Saar et al. (1997)</a> performed a whole-genome screen in 14 NBS/BBS families and localized the causative gene to a 1-cM interval on 8q21, between markers D8S271 and D8S270, with a peak lod score of 6.86 at D8S1811. This marker also showed strong allelic association to both Slavic NBS and German BBS patients, suggesting the existence of one major mutation of Slavic origin. The authors stated that since the same allele is seen in both complementation groups, genetic homogeneity of NBS/BBS can be considered as proved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Matsuura, S., Weemaes, C., Smeets, D., Takami, H., Kondo, N., Sakamoto, S., Yano, N., Nakamura, A., Tauchi, H., Endo, S., Oshimura, M., Komatsu, K. <strong>Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24.</strong> Am. J. Hum. Genet. 60: 1487-1494, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199571</a>] [<a href="https://doi.org/10.1086/515461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199571">Matsuura et al. (1997)</a> used microcell-mediated chromosome transfer followed by complementation assays based on radiosensitivity to demonstrate that only chromosome 8 complements the sensitivity to ionizing radiation in NBS cell lines. In complementation assays performed after the transfer of a reduced chromosome, merely the long arm of chromosome 8 was sufficient for restoring the defect. The results supported the suggestion that NBS is a homogeneous disorder and that the gene for NBS is located at 8q21-q24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a geographically diverse group of NBS patients, <a href="#2" class="mim-tip-reference" title="Cerosaletti, K. M., Lange, E., Stringham, H. M., Weemaes, C. M. R., Smeets, D., Solder, B., Belohradsky, B. H., Taylor, A. M. R., Karnes, P., Elliott, A., Komatsu, K., Gatti, R. A., Boehnke, M., Concannon, P. <strong>Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.</strong> Am. J. Hum. Genet. 63: 125-134, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634525</a>] [<a href="https://doi.org/10.1086/301927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634525">Cerosaletti et al. (1998)</a> reported linkage to 8q21 in 6 of 7 families, with a maximum lod score of 3.58. Significant linkage disequilibrium was detected for 8 of 13 markers tested in the 8q21 region, including D8S1811. To localize the gene for NBS further, they generated a radiation hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that placed the NBS gene between D8S1757 and D8S270. A common founder haplotype was present in 15 of 18 disease chromosomes from 9 of 11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggested that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The similarity of cellular and chromosomal symptoms between AT and variant AT suggests that the NBS gene is a radiosensitivity gene and that both the AT and the NBS genes may be part of the same protein complex or pathway. <a href="#21" class="mim-tip-reference" title="Stumm, M., Sperling, K., Wegner, R.-D. <strong>Noncomplementation of radiation-induced chromosome aberrations in ataxia-telangiectasia/ataxia-telangiectasia-variant heterodikaryons. (Letter)</strong> Am. J. Hum. Genet. 60: 1246-1251, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150175</a>]" pmid="9150175">Stumm et al. (1997)</a> found noncomplementation of radiation-induced chromosome aberrations in heterodikaryons between ataxia-telangiectasia and ataxia-telangiectasia variant cells. They suggested that the results of noncomplementation in AT/AT-V cell hybrids could be explained best by genes whose products contribute to a multisubunit protein involved in the damage response of radiation-induced chromosome aberrations. The data supported the assumption that the AT-V disorders represent a homogeneous genetic trait. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of NBS in the families reported by <a href="#29" class="mim-tip-reference" title="Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K. M., Chrzanowska, K. H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P. R., Nowak, N. J., Stumm, M., Weemaes, C. M. R., Gatti, R. A., Wilson, R. K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P., Reis, A. <strong>Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.</strong> Cell 93: 467-476, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590180</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81174-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590180">Varon et al. (1998)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590180" 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="#29" class="mim-tip-reference" title="Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K. M., Chrzanowska, K. H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P. R., Nowak, N. J., Stumm, M., Weemaes, C. M. R., Gatti, R. A., Wilson, R. K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P., Reis, A. <strong>Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.</strong> Cell 93: 467-476, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590180</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81174-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590180">Varon et al. (1998)</a> and <a href="#1" class="mim-tip-reference" title="Carney, J. P., Maser, R. S., Olivares, H., Davis, E. M., Le Beau, M., Yates, J. R., III, Hays, L., Morgan, W. F., Petrini, J. H. J. <strong>The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.</strong> Cell 93: 477-486, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590181</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81175-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590181">Carney et al. (1998)</a> isolated the gene responsible for the Nijmegen breakage syndrome. In patients with NBS, <a href="#29" class="mim-tip-reference" title="Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K. M., Chrzanowska, K. H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P. R., Nowak, N. J., Stumm, M., Weemaes, C. M. R., Gatti, R. A., Wilson, R. K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P., Reis, A. <strong>Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.</strong> Cell 93: 467-476, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590180</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81174-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590180">Varon et al. (1998)</a> identified mutations in the nibrin/p95 gene (see, e.g., 657del5; <a href="/entry/602667#0001">602667.0001</a>). In the patient reported by <a href="#12" class="mim-tip-reference" title="Maraschio, P., Peretti, D., Lambiase, S., Lo Curto, F., Caufin, D., Gargantini, L., Minoli, L., Zuffardi, O. <strong>A new chromosome instability disorder.</strong> Clin. Genet. 30: 353-365, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3802554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3802554</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1986.tb01892.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3802554">Maraschio et al. (1986)</a>, <a href="#28" class="mim-tip-reference" title="Varon, R., Dutrannoy, V., Weikert, G., Tanzarella, C., Antoccia, A., Stockl, L., Spadoni, E., Kruger, L.-A., di Masi, A., Sperling, K., Digweed, M., Maraschio, P. <strong>Mild Nijmegen breakage syndrome phenotype due to alternative splicing.</strong> Hum. Molec. Genet. 15: 679-689, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415040</a>] [<a href="https://doi.org/10.1093/hmg/ddi482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415040">Varon et al. (2006)</a> identified a homozygous hypomorphic mutation in the NBN gene (<a href="/entry/602667#0010">602667.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3802554+9590180+16415040+9590181" 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 monozygotic twin brothers with a severe form of NBS without chromosomal instability, <a href="#18" class="mim-tip-reference" title="Seemanova, E., Sperling, K., Neitzel, H., Varon, R., Hadac, J., Butova, O., Schrock, E., Seeman, P., Digweed, M. <strong>Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability.</strong> J. Med. Genet. 43: 218-224, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16033915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16033915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16033915[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/10.1136/jmg.2005.035287" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16033915">Seemanova et al. (2006)</a> identified compound heterozygosity for the major 657del5 mutation and a missense mutation (R215W; <a href="/entry/602667#0009">602667.0009</a>) in the NBS1 gene. The infants were small for gestational age and microcephalic; ultrasound revealed enlarged, mildly asymmetric lateral ventricles, enlarged subarachnoid areas, and poor gyrification of the brain. Psychomotor development was severely retarded in both boys. <a href="#18" class="mim-tip-reference" title="Seemanova, E., Sperling, K., Neitzel, H., Varon, R., Hadac, J., Butova, O., Schrock, E., Seeman, P., Digweed, M. <strong>Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability.</strong> J. Med. Genet. 43: 218-224, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16033915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16033915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16033915[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/10.1136/jmg.2005.035287" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16033915">Seemanova et al. (2006)</a> postulated that the severity of the phenotype was due to the R215W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16033915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Maraschio, P., Spadoni, E., Tanzarella, C., Antoccia, A., di Masi, A., Maghnie, M., Varon, R., Demuth, I., Tiepolo, L., Danesino, C. <strong>Genetic heterogeneity for a Nijmegen breakage-like syndrome.</strong> Clin. Genet. 63: 283-290, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702161</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00054.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702161">Maraschio et al. (2003)</a> confirmed genetic heterogeneity for NBS by demonstrating lack of mutation in either the NBS1 or the LIG4 gene in a patient with a typical NBS phenotype. The patient showed intrauterine growth retardation and was born with bilateral inguinal hernia, right cryptorchidism, and curved penis with hypospadias, all of which required surgical treatment. He was seen at the age of 9 months for growth and developmental delay and facial dysmorphism. Facial features included upslanted palpebral fissures, prominent nasal bridge, large mouth with thin upper lip and everted lower lip, and micrognathia. In the proband's blood samples, the frequency of abnormal metaphases was found to vary between 5% and 22%, with a mean value of 10.4%, on a total of 501 observed metaphases. Aberrations consisted mainly of chromatid breaks and chromosome breaks. A slightly increased frequency of chromatid breaks was observed in both parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Heterozygosity</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Cheung, V. G., Ewens, W. J. <strong>Heterozygous carriers of Nijmegen breakage syndrome have a distinct gene expression phenotype.</strong> Genome Res. 16: 973-979, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16809669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16809669</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16809669[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/10.1101/gr.5320706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16809669">Cheung and Ewens (2006)</a> found 520 genes with expression levels that differed significantly (p less than 0.001) between heterozygous NBS mutation carriers and controls. By linear discrimination analysis, they identified a combination of 16 genes that allowed 100% correct classification of individuals as either carriers or noncarriers. <a href="#3" class="mim-tip-reference" title="Cheung, V. G., Ewens, W. J. <strong>Heterozygous carriers of Nijmegen breakage syndrome have a distinct gene expression phenotype.</strong> Genome Res. 16: 973-979, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16809669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16809669</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16809669[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/10.1101/gr.5320706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16809669">Cheung and Ewens (2006)</a> concluded that NBS carriers have a specific gene expression phenotype, and suggested that heterozygous mutations can contribute significantly to natural variation in gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16809669" 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>Some of the patients studied by <a href="#16" class="mim-tip-reference" title="Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K. <strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong> Am. J. Hum. Genet. 60: 605-610, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042920</a>]" pmid="9042920">Saar et al. (1997)</a> were Germans in whom the Berlin breakage syndrome had been described and others were Slavic patients in whom the Seemanova syndrome (a synonym for NBS) had been described. <a href="#16" class="mim-tip-reference" title="Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K. <strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong> Am. J. Hum. Genet. 60: 605-610, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042920</a>]" pmid="9042920">Saar et al. (1997)</a> noted that it would be interesting to investigate whether Dutch patients also showed an allelic association at D8S1811, similar to what they had found in Slavic and German patients. In the first half of the 17th century, after the battle of Weissenberg in the Thirty Years War, a considerable number of Bohemian Protestants emigrated to the Netherlands from an area presently part of Poland and the Czech Republic. A major NBS mutation may have found its way to the Netherlands by migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042920" 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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Carney, J. P., Maser, R. S., Olivares, H., Davis, E. M., Le Beau, M., Yates, J. R., III, Hays, L., Morgan, W. F., Petrini, J. H. J.
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<strong>The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.</strong>
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Cell 93: 477-486, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590181</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590181" 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/s0092-8674(00)81175-7" target="_blank">Full Text</a>]
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Cerosaletti, K. M., Lange, E., Stringham, H. M., Weemaes, C. M. R., Smeets, D., Solder, B., Belohradsky, B. H., Taylor, A. M. R., Karnes, P., Elliott, A., Komatsu, K., Gatti, R. A., Boehnke, M., Concannon, P.
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<strong>Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.</strong>
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Am. J. Hum. Genet. 63: 125-134, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634525" 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/10.1086/301927" target="_blank">Full Text</a>]
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Cheung, V. G., Ewens, W. J.
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<strong>Heterozygous carriers of Nijmegen breakage syndrome have a distinct gene expression phenotype.</strong>
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Genome Res. 16: 973-979, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16809669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16809669</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16809669[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=16809669" 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/10.1101/gr.5320706" target="_blank">Full Text</a>]
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Chrzanowska, K. H., Kleijer, W. J., Krajewska-Walasek, M., Bialecka, M., Gutkowska, A., Goryluk-Kozakiewicz, B., Michalkiewicz, J., Stachowski, J., Gregorek, H., Lyson-Wojciechowska, G., Janowicz, W., Jozwiak, S.
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<strong>Eleven Polish patients with microcephaly, immunodeficiency and chromosomal instability: the Nijmegen breakage syndrome.</strong>
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Am. J. Med. Genet. 57: 462-471, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545870" 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.1320570321" target="_blank">Full Text</a>]
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Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W.
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<strong>A chromosome breakage syndrome with profound immunodeficiency.</strong>
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Blood 67: 1251-1256, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2421804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2421804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2421804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Curry, C. J. R., O'Lague, P., Tsai, J., Hutchison, H. T., Jaspers, N. G. J., Wara, D., Gatti, R. A.
|
|
<strong>AT(Fresno): a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome.</strong>
|
|
Am. J. Hum. Genet. 45: 270-275, 1989. Note: Erratum: Am. J. Hum. Genet. 45: 663 only, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2491181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2491181</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2491181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Der Kaloustian1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Der Kaloustian, V. M., Kleijer, W., Booth, A., Auerbach, A. D., Mazer, B., Elliott, A. M., Abish, S., Usher, R., Watters, G., Vekemans, M., Eydoux, P.
|
|
<strong>Possible new variant of Nijmegen breakage syndrome.</strong>
|
|
Am. J. Med. Genet. 65: 21-26, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8914736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8914736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8914736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1<21::AID-AJMG3>3.0.CO;2-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Jaspers1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jaspers, N. G. J., Gatti, R. A., Baan, C., Linssen, P. C. M. L., Bootsma, D.
|
|
<strong>Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients.</strong>
|
|
Cytogenet. Cell Genet. 49: 259-263, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3248383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3248383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3248383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132673" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Jaspers1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jaspers, N. G. J., Taalman, R. D. F. M., Baan, C.
|
|
<strong>Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia.</strong>
|
|
Am. J. Hum. Genet. 42: 66-73, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3337113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3337113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3337113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kleier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kleier, S., Herrmann, M., Wittwer, B., Varon, R., Reis, A., Horst, J.
|
|
<strong>Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome.</strong>
|
|
Clin. Genet. 57: 384-387, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10852373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10852373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10852373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2000.570509.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Komatsu1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Komatsu, K., Matsuura, S., Tauchi, H., Endo, S., Kodama, S., Smeets, D., Weemaes, C., Oshimura, M.
|
|
<strong>The gene for Nijmegen breakage syndrome (V2) is not located on chromosome 11. (Letter)</strong>
|
|
Am. J. Hum. Genet. 58: 885-888, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8644753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Maraschio1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maraschio, P., Peretti, D., Lambiase, S., Lo Curto, F., Caufin, D., Gargantini, L., Minoli, L., Zuffardi, O.
|
|
<strong>A new chromosome instability disorder.</strong>
|
|
Clin. Genet. 30: 353-365, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3802554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3802554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3802554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1986.tb01892.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Maraschio2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maraschio, P., Spadoni, E., Tanzarella, C., Antoccia, A., di Masi, A., Maghnie, M., Varon, R., Demuth, I., Tiepolo, L., Danesino, C.
|
|
<strong>Genetic heterogeneity for a Nijmegen breakage-like syndrome.</strong>
|
|
Clin. Genet. 63: 283-290, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00054.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Matsuura1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsuura, S., Weemaes, C., Smeets, D., Takami, H., Kondo, N., Sakamoto, S., Yano, N., Nakamura, A., Tauchi, H., Endo, S., Oshimura, M., Komatsu, K.
|
|
<strong>Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24.</strong>
|
|
Am. J. Hum. Genet. 60: 1487-1494, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/515461" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Meyer2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, S., Kingston, H., Taylor, A. M. R., Byrd, P. J., Last, J. I. K., Brennan, B. M. D., Trueman, S., Kelsey, A., Taylor, G. M., Eden, O. B.
|
|
<strong>Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site.</strong>
|
|
Cancer Genet. Cytogenet. 154: 169-174, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15474156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15474156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15474156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.022" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Saar1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K.
|
|
<strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong>
|
|
Am. J. Hum. Genet. 60: 605-610, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042920</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Seemanova1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seemanova, E., Passarge, E., Beneskova, D., Houstek, J., Kasal, P., Sevcikova, M.
|
|
<strong>Familial microcephaly with normal intelligence, immunodeficiency, and risk of lymphoreticular malignancies: a new autosomal recessive disorder.</strong>
|
|
Am. J. Med. Genet. 20: 639-648, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3857858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3857858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3857858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320200410" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Seemanova2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seemanova, E., Sperling, K., Neitzel, H., Varon, R., Hadac, J., Butova, O., Schrock, E., Seeman, P., Digweed, M.
|
|
<strong>Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability.</strong>
|
|
J. Med. Genet. 43: 218-224, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16033915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16033915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16033915[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=16033915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2005.035287" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Sperling1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sperling, K.
|
|
<strong>Analisi dell' eterogeneita nell'uomo.</strong>
|
|
Prospettive Pediat. 49: 53-66, 1983.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Stumm1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stumm, M., Gatti, R. A., Reis, A., Udar, N., Chrzanowska, K., Seemanova, E., Sperling, K., Wegner, R.-D.
|
|
<strong>The ataxia-telangiectasia-variant genes 1 and 2 are distinct from the ataxia-telangiectasia gene on chromosome 11q23.1. (Letter)</strong>
|
|
Am. J. Hum. Genet. 57: 960-962, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Stumm1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stumm, M., Sperling, K., Wegner, R.-D.
|
|
<strong>Noncomplementation of radiation-induced chromosome aberrations in ataxia-telangiectasia/ataxia-telangiectasia-variant heterodikaryons. (Letter)</strong>
|
|
Am. J. Hum. Genet. 60: 1246-1251, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Taalman1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taalman, R. D. F. M., Hustinx, T. W. J., Weemaes, C. M. R., Seemanova, E., Schmidt, A., Passarge, E., Scheres, J. M. J. C.
|
|
<strong>Further delineation of the Nijmegen breakage syndrome.</strong>
|
|
Am. J. Med. Genet. 32: 425-431, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320320332" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Tanzarella2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tanzarella, C., Antoccia, A., Spadoni, E., di Masi, A., Pecile, V., Demori, E., Varon, R., Marseglia, G. L., Tiepolo, L., Maraschio, P.
|
|
<strong>Chromosome instability and nibrin protein variants in NBS heterozygotes.</strong>
|
|
Europ. J. Hum. Genet. 11: 297-303, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12708449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12708449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12708449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200962" target="_blank">Full Text</a>]
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<a id="24" class="mim-anchor"></a>
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<a id="Teebi1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Teebi, A. S., Al-Awadi, S. A., White, A. G.
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<strong>Autosomal recessive nonsyndromal microcephaly with normal intelligence.</strong>
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Am. J. Med. Genet. 26: 355-359, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3812587" 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.1320260214" target="_blank">Full Text</a>]
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<a id="25" class="mim-anchor"></a>
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<a id="Tekin2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tekin, M., Dogu, F., Tacyildiz, N., Akar, E., Ikinciogullari, A., Ogur, G., Yavuz, G., Babacan, E., Akar, N.
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<strong>657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.</strong>
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Clin. Genet. 62: 84-88, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12123493" 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/10.1034/j.1399-0004.2002.620112.x" target="_blank">Full Text</a>]
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<a id="26" class="mim-anchor"></a>
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<a id="Tupler1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tupler, R., Marseglia, G. L., Stefanini, M., Prosperi, E., Chessa, L., Nardo, T., Marchi, A., Maraschio, P.
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<strong>A variant of the Nijmegen breakage syndrome with unusual cytogenetic features and intermediate cellular radiosensitivity.</strong>
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J. Med. Genet. 34: 196-202, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9132489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9132489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9132489" 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.34.3.196" target="_blank">Full Text</a>]
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<a id="27" class="mim-anchor"></a>
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<a id="van der Burgt1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van der Burgt, I., Chrzanowska, K. H., Smeets, D., Weemaes, C.
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<strong>Nijmegen breakage syndrome.</strong>
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J. Med. Genet. 33: 153-156, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8929954" 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.33.2.153" target="_blank">Full Text</a>]
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<a id="Varon2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Varon, R., Dutrannoy, V., Weikert, G., Tanzarella, C., Antoccia, A., Stockl, L., Spadoni, E., Kruger, L.-A., di Masi, A., Sperling, K., Digweed, M., Maraschio, P.
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<strong>Mild Nijmegen breakage syndrome phenotype due to alternative splicing.</strong>
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Hum. Molec. Genet. 15: 679-689, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415040" 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/hmg/ddi482" target="_blank">Full Text</a>]
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<a id="29" class="mim-anchor"></a>
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<a id="Varon1998" class="mim-anchor"></a>
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<p class="mim-text-font">
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Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K. M., Chrzanowska, K. H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P. R., Nowak, N. J., Stumm, M., Weemaes, C. M. R., Gatti, R. A., Wilson, R. K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P., Reis, A.
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<strong>Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.</strong>
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Cell 93: 467-476, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590180" 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/s0092-8674(00)81174-5" target="_blank">Full Text</a>]
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<a id="30" class="mim-anchor"></a>
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<a id="Weemaes1981" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C., van Munster, P. J. J., Bakkeren, J. A. J. M., Taalman, R. D. F. M.
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<strong>A new chromosomal instability disorder: the Nijmegen breakage syndrome.</strong>
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Acta Paediat. Scand. 70: 557-564, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7315300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7315300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7315300" 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.1651-2227.1981.tb05740.x" target="_blank">Full Text</a>]
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<a id="31" class="mim-anchor"></a>
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<a id="Wegner1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wegner, R.-D., Metzger, M., Hanefeld, F., Jaspers, N. G. J., Baan, C., Magdorf, K., Kunze, J., Sperling, K.
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<strong>A new chromosomal instability disorder confirmed by complementation studies.</strong>
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Clin. Genet. 33: 20-32, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3277755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3277755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3277755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="32" class="mim-anchor"></a>
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<a id="Woods1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Woods, C. G., Leversha, M., Rogers, J. G.
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<strong>Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.</strong>
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J. Med. Genet. 32: 301-305, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643362</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7643362" 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.32.4.301" target="_blank">Full Text</a>]
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 11/2/2009
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 8/30/2006<br>Marla J. F. O'Neill - updated : 4/19/2006<br>Victor A. McKusick - updated : 1/31/2005<br>Natalie E. Krasikov - updated : 6/1/2004<br>Cassandra L. Kniffin - reorganized : 10/27/2003<br>Victor A. McKusick - updated : 5/12/2003<br>Victor A. McKusick - updated : 7/20/1998<br>Stylianos E. Antonarakis - updated : 5/29/1998<br>Victor A. McKusick - updated : 5/27/1998<br>Victor A. McKusick - updated : 6/16/1997<br>Victor A. McKusick - updated : 4/21/1997<br>Victor A. McKusick - updated : 3/13/1997<br>Iosif W. Lurie - updated : 1/6/1997
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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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 : 6/4/1986
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 09/29/2023
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<span class="mim-text-font">
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carol : 12/14/2022<br>carol : 01/07/2016<br>tpirozzi : 7/12/2013<br>terry : 3/14/2013<br>terry : 3/14/2013<br>terry : 4/12/2012<br>wwang : 11/5/2009<br>ckniffin : 11/2/2009<br>terry : 2/12/2009<br>wwang : 6/22/2007<br>terry : 6/21/2007<br>carol : 8/30/2006<br>carol : 8/30/2006<br>terry : 8/30/2006<br>wwang : 4/20/2006<br>terry : 4/19/2006<br>tkritzer : 2/4/2005<br>terry : 1/31/2005<br>carol : 6/1/2004<br>carol : 10/27/2003<br>ckniffin : 10/7/2003<br>carol : 5/15/2003<br>tkritzer : 5/14/2003<br>terry : 5/12/2003<br>terry : 4/28/2003<br>ckniffin : 3/11/2003<br>mgross : 7/22/1999<br>terry : 5/20/1999<br>carol : 7/21/1998<br>terry : 7/20/1998<br>carol : 6/3/1998<br>carol : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/27/1998<br>alopez : 5/13/1998<br>mark : 11/11/1997<br>jenny : 10/24/1997<br>terry : 6/23/1997<br>terry : 6/17/1997<br>terry : 6/16/1997<br>alopez : 4/21/1997<br>alopez : 4/17/1997<br>alopez : 4/17/1997<br>terry : 4/11/1997<br>terry : 3/14/1997<br>terry : 3/13/1997<br>terry : 3/11/1997<br>jamie : 1/7/1997<br>jamie : 1/6/1997<br>mark : 4/3/1996<br>terry : 3/29/1996<br>terry : 3/29/1996<br>mark : 1/17/1996<br>terry : 1/16/1996<br>mark : 12/20/1995<br>terry : 10/30/1995<br>mark : 10/23/1995<br>mimadm : 2/19/1994<br>supermim : 3/17/1992<br>carol : 7/9/1991<br>supermim : 10/16/1990
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<h3>
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<span class="mim-font">
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<strong>#</strong> 251260
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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NIJMEGEN BREAKAGE SYNDROME; NBS
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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ATAXIA-TELANGIECTASIA VARIANT V1; AT-V1<br />
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MICROCEPHALY WITH NORMAL INTELLIGENCE, IMMUNODEFICIENCY, AND LYMPHORETICULAR MALIGNANCIES<br />
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SEEMANOVA SYNDROME II<br />
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NONSYNDROMAL MICROCEPHALY, AUTOSOMAL RECESSIVE, WITH NORMAL INTELLIGENCE<br />
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IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY
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</span>
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</h4>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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<span class="h3 mim-font">
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BERLIN BREAKAGE SYNDROME, INCLUDED; BBS, INCLUDED
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<span class="h4 mim-font">
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ATAXIA-TELANGIECTASIA VARIANT V2, INCLUDED; AT-V2, INCLUDED
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 234638009;
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<strong>ORPHA:</strong> 647;
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<strong>DO:</strong> 7400;
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</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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<th>
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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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Gene/Locus
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<td>
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<span class="mim-font">
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8q21.3
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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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Nijmegen breakage 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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251260
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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NBN
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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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602667
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</span>
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</td>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because Nijmegen breakage syndrome (NBS) is caused by homozygous or compound heterozygous mutation in the NBS1 gene (NBN; 602667) on chromosome 8q21.</p>
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<h4>
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<strong>Description</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The Nijmegen breakage syndrome (NBS) and the phenotypically indistinguishable Berlin breakage syndrome (BBS) are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. Cells from NBS/BBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia (AT; 208900), but NBS/BBS patients have a distinct clinical phenotype.</p><p>The clinical features of LIG4 syndrome (606593), caused by mutation in the LIG4 gene (601837), resemble those of NBS.</p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Patients with AT variant-1 are clinically indistinguishable from those with AT variant-2. These patients share mitogenic features with AT, such as spontaneous chromosomal instability, clonal occurrence of rearrangements involving, in particular, chromosomes 7 and 14, chromosomal and cellular hypersensitivity to irradiation, and radioresistant DNA synthesis. However, patients with AT-V have neither ataxia nor telangiectasia, and are characterized by pronounced microcephaly, microgenia, 'bird-like' facies, immunodeficiency, and normal serum levels of alpha-fetoprotein. V1 and V2 are distinguished from one another only by complementation analysis (Wegner et al., 1988; Saar et al., 1997). </p><p>Weemaes et al. (1981) described 2 sons of second-cousin parents who had microcephaly, stunted growth, mental retardation, cafe-au-lait spots, and immunodeficiency. Cytogenetic studies showed a typical form of chromosome instability with multiple rearrangements of chromosomes 7 and 14. A lower frequency of the same chromosome abnormalities was found in the father and 3 of the phenotypically normal sibs. Seemanova et al. (1985) described 9 patients in 6 families with a 'new' disorder characterized by low birth weight for dates, microcephaly with normal intelligence, receding mandibula, cellular and humoral immune defects, and increased risk of lymphoreticular malignancies. No evidence of chromosomal instability was found, but chromosome analysis was difficult because the rate of blastic transformation with phytohemagglutinin was low. Even sex ratio, consanguinity in 1 family and grandparental isonymy in a second, and the occurrence of 2 affected sibs in 3 families supported autosomal recessive inheritance. Bronchiectasis, pneumonia, otitis media, mastoiditis, and sinusitis occurred. Immunoglobulin levels were reduced. In 2 sibs, acute lymphoblastic leukemia developed at ages 9 years and 12 months, respectively. Generalized malignancies, apparently originating in the mediastinum and variously identified as malignant lymphogranuloma, acute undifferentiated hemoblastoma and mediastinal blastoma (probably neuroblastoma) was the cause of death in several. The oldest surviving patient of 4 was 12.5 years old. </p><p>Conley et al. (1986) described a 21-year-old woman with growth failure, immunodeficiency, and chromosomal breakage syndrome involving chromosomes 7 and 14. </p><p>Maraschio et al. (1986) described the case of a 31-year-old woman with primary amenorrhea, microcephaly and immunodeficiency. Her healthy parents were related as first cousins once removed. A younger sister, who also had primary amenorrhea, had died at age 20 years with a malignant lymphoma. Chromosome studies revealed a high proportion of metaphases with multiple chromosome aberrations. The same unbalanced translocation, t(8q;21q), was present in about 59% of metaphases. A few rearrangements involving chromosomes 7 and 14, similar to those described in patients with ataxia-telangiectasia, were found. Sister chromatid exchanges were not increased. </p><p>Teebi et al. (1987) reported a large inbred Arab kindred in which 8 individuals in 5 sibships had microcephaly and normal intelligence. Two died of acute lymphoreticular malignancy or bronchial pneumonia. Immunologic and chromosomal studies carried out in 3 affected living sibs yielded normal results. Taalman et al. (1989) reported the findings in 5 families, 2 from the Netherlands and 3 from Czechoslovakia, containing a total of 8 patients with NBS. The patients had microcephaly, short stature, a 'bird-like' face, and immunologic defects. The basic karyotype in these patients was normal, but in a fifth or more of metaphases, rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all 5 living patients were very sensitive to ionizing radiation. </p><p>Chrzanowska et al. (1995) reported 11 patients with Nijmegen breakage syndrome from 8 independent Polish families, with a total of 3 pairs of affected sibs. The clinical pattern included microcephaly, particular 'bird-like' face, growth retardation, and, in some cases, mild to moderate mental deficiency. Most of the patients had recurrent respiratory tract infections. One girl developed B-cell lymphoma. Chromosome studies showed structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14, in a proportion of metaphase in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were studied from this point of view. </p><p>The clinical, immunologic, chromosomal, and cell-biologic findings in 42 patients in the NBS Registry in Nijmegen were reviewed by van der Burgt et al. (1996). Although the immunologic, chromosomal, and cell-biologic findings resembled those in AT, the clinical findings were quite different. The authors stated that NBS appears to be a separate entity that is not allelic to AT, as indicated by the fact that linkage studies exclude 11q22-q23, where the gene for ataxia-telangiectasia is located, as the site of the NBS gene. None of the patients had signs of cerebellar ataxia, apraxic eye movements, or other neurologic abnormalities except for twin girls described by Curry et al. (1989) who had clinical symptoms of both NBS and AT (see 607585.0014). Complementation studies assigned these cases to NBS complementation group V1. Subtle scleral telangiectasia was noted in 10 of 25 patients. The patients did not have raised serum AFP levels, as in ataxia-telangiectasia. Twelve patients varying in age from 1 to 22 years had developed lymphoma. One patient developed a glioma at the age of 12 years, 1 patient a medulloblastoma at 15 years, and 1 patient a rhabdomyosarcoma at 4 years. </p><p>Der Kaloustian et al. (1996) described a boy who in addition to typical manifestations had penoscrotal hypospadias. He had lymphopenia with low percentage of B and T cells, absence of IgE, and low response to mitogen stimulation. At the age of 4 years he developed rhabdomyosarcoma. Cytogenetic study showed multiple chromatid and chromosome breaks, structural rearrangements involving mainly chromosomes 7 and 14, and different monosomies in 57 to 58% of cells. Nijmegen breakage syndrome was diagnosed, although hypospadias and a high percentage of monosomic cells led the authors to suggest he represented a specific variant of this syndrome. Der Kaloustian et al. (1996) suggested that the boy described by Woods et al. (1995) as a patient with Seckel syndrome might have the same variant of Nijmegen breakage syndrome. </p><p>Meyer et al. (2004) described a 7-year-old girl with NBS who was homozygous for the NBS1 698del4 mutation (602667.0002). She had been diagnosed with perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from chemotherapy. RMS arising perianally is exceedingly uncommon but had previously been described in 2 cases of NBS (Der Kaloustian et al., 1996; Tekin et al., 2002). Thus, association with NBS should be considered when a perianal RMS is encountered. </p><p>Tupler et al. (1997) provided the first report of an Italian case of Nijmegen breakage syndrome. The proband was an immunodeficient, microcephalic, 11-year-old boy with a 'bird-like' face. He developed a T-cell-rich B-cell lymphoma. Spontaneous chromosomal instability was detected in T- and B-lymphocytes and in fibroblasts; chromosomes 7 and 14 were only sporadically involved in the rearrangements and no clonal abnormality was present. The patient appeared to be sensitive both to ionizing radiation and to bleomycin, although his sensitivity did not reach the level of ataxia-telangiectasia reference cells. Although the clinical evaluation suggested to Tupler et al. (1997) a diagnosis of NBS, differences in the cytogenetic and cell-biologic data suggested that the patient might have an allelic form of the disorder. </p><p>To evaluate the possibility of carrier detection, Tanzarella et al. (2003) studied heterozygous individuals from 3 unrelated NBS families with distinct gene deletion mutations for the frequency of spontaneous chromosome abnormalities in blood lymphocytes, x-ray G2 sensitivity in lymphoblastoid cell lines, and the ability to detect nibrin variants by immunoprecipitation and immunoblotting. All 13 heterozygotes showed chromosomal instability (chromatid and chromosomal breaks as well as rearrangements), but 7 of 8 tested were similar to controls in radiosensitivity. Immunoprecipitation of nibrin detected the normal and variant proteins in carriers from all 3 families, but immunoblotting was not as discriminating. </p><p><strong><em>Complementation Groups</em></strong></p><p>
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Jaspers et al. (1988) studied fibroblast cultures from 6 unrelated patients with immunodeficiency, developmental delay, microcephaly, and chromosomal instability; 1 of the patients had been described by Weemaes et al. (1981), 1 by Sperling (1983), 3 by Seemanova et al. (1985), and 1 by Conley et al. (1986). The cells showed radiosensitivity, clonogenic cell survival, and abnormal inhibition of DNA synthesis. Fibroblasts from all cases showed complementation with the 5 complementation groups of AT. Cross-complementation studies within the group indicated the existence of 2 separate complementation groups, designated V1 and V2, that were genetically distinct from AT. The case of Conley et al. (1986) and 1 case of Sperling (1983) showed complementation with the other cases, and were therefore classified as having V2. The patient of Sperling (1983) was further studied by Wegner et al. (1988). Wegner et al. (1988) reported 2 sibs with a syndrome identical to that in the patient reported by Conley et al. (1986), as shown by complementation studies. These patients had V2. </p><p>Jaspers et al. (1988) performed complementation studies on fibroblast strains from 50 patients with either AT or NBS. Using the radioresistant DNA replication characteristic as a marker, they demonstrated 6 different genetic complementation groups, 2 of which, groups V1 and V2, involved patients with NBS. An individual with clinical symptoms of both AT and NBS was found in group V2, indicating that the 2 disorders are closely related. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the treatment of malignancies in patients with NBS, van der Burgt et al. (1996) stated that cytostatics are the first choice; however, radiomimetics (for example, bleomycin) should be avoided, and the chemotherapy doses should be reduced. Radiation therapy should be avoided, since x-irradiation can induce malignancies in NBS patients. </p>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Kleier et al. (2000) pointed out that rearrangements involving chromosomes 7 and 14 occur in both ataxia-telangiectasia and NBS. However, NBS patients show characteristic microcephaly, which is rare in ataxia-telangiectasia, and they do not develop ataxia and telangiectasia. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In 6 of the affected Polish families reported by Chrzanowska et al. (1995), Stumm et al. (1995) performed haplotype studies and sib-pair analysis and demonstrated lack of linkage to the 11q22-q23 region where the AT locus maps. One of these families had been assigned to complementation group AT-V1 and a second to complementation group AT-V2 by cell-fusion studies. No complementation studies had been done in the other 4 families. Komatsu et al. (1996) likewise excluded the ATM locus on chromosome 11 as the site of the mutation in AT-V2. They found that the sensitivity of V2 cells to radiation is unchanged after the transfer of an extra copy of a normal chromosome 11 into the cells. </p><p>Saar et al. (1997) performed a whole-genome screen in 14 NBS/BBS families and localized the causative gene to a 1-cM interval on 8q21, between markers D8S271 and D8S270, with a peak lod score of 6.86 at D8S1811. This marker also showed strong allelic association to both Slavic NBS and German BBS patients, suggesting the existence of one major mutation of Slavic origin. The authors stated that since the same allele is seen in both complementation groups, genetic homogeneity of NBS/BBS can be considered as proved. </p><p>Matsuura et al. (1997) used microcell-mediated chromosome transfer followed by complementation assays based on radiosensitivity to demonstrate that only chromosome 8 complements the sensitivity to ionizing radiation in NBS cell lines. In complementation assays performed after the transfer of a reduced chromosome, merely the long arm of chromosome 8 was sufficient for restoring the defect. The results supported the suggestion that NBS is a homogeneous disorder and that the gene for NBS is located at 8q21-q24. </p><p>In a geographically diverse group of NBS patients, Cerosaletti et al. (1998) reported linkage to 8q21 in 6 of 7 families, with a maximum lod score of 3.58. Significant linkage disequilibrium was detected for 8 of 13 markers tested in the 8q21 region, including D8S1811. To localize the gene for NBS further, they generated a radiation hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that placed the NBS gene between D8S1757 and D8S270. A common founder haplotype was present in 15 of 18 disease chromosomes from 9 of 11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggested that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88. </p>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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</h4>
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<span class="mim-text-font">
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<p>The similarity of cellular and chromosomal symptoms between AT and variant AT suggests that the NBS gene is a radiosensitivity gene and that both the AT and the NBS genes may be part of the same protein complex or pathway. Stumm et al. (1997) found noncomplementation of radiation-induced chromosome aberrations in heterodikaryons between ataxia-telangiectasia and ataxia-telangiectasia variant cells. They suggested that the results of noncomplementation in AT/AT-V cell hybrids could be explained best by genes whose products contribute to a multisubunit protein involved in the damage response of radiation-induced chromosome aberrations. The data supported the assumption that the AT-V disorders represent a homogeneous genetic trait. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The transmission pattern of NBS in the families reported by Varon et al. (1998) was consistent with autosomal recessive inheritance. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>Varon et al. (1998) and Carney et al. (1998) isolated the gene responsible for the Nijmegen breakage syndrome. In patients with NBS, Varon et al. (1998) identified mutations in the nibrin/p95 gene (see, e.g., 657del5; 602667.0001). In the patient reported by Maraschio et al. (1986), Varon et al. (2006) identified a homozygous hypomorphic mutation in the NBN gene (602667.0010). </p><p>In monozygotic twin brothers with a severe form of NBS without chromosomal instability, Seemanova et al. (2006) identified compound heterozygosity for the major 657del5 mutation and a missense mutation (R215W; 602667.0009) in the NBS1 gene. The infants were small for gestational age and microcephalic; ultrasound revealed enlarged, mildly asymmetric lateral ventricles, enlarged subarachnoid areas, and poor gyrification of the brain. Psychomotor development was severely retarded in both boys. Seemanova et al. (2006) postulated that the severity of the phenotype was due to the R215W mutation. </p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
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Maraschio et al. (2003) confirmed genetic heterogeneity for NBS by demonstrating lack of mutation in either the NBS1 or the LIG4 gene in a patient with a typical NBS phenotype. The patient showed intrauterine growth retardation and was born with bilateral inguinal hernia, right cryptorchidism, and curved penis with hypospadias, all of which required surgical treatment. He was seen at the age of 9 months for growth and developmental delay and facial dysmorphism. Facial features included upslanted palpebral fissures, prominent nasal bridge, large mouth with thin upper lip and everted lower lip, and micrognathia. In the proband's blood samples, the frequency of abnormal metaphases was found to vary between 5% and 22%, with a mean value of 10.4%, on a total of 501 observed metaphases. Aberrations consisted mainly of chromatid breaks and chromosome breaks. A slightly increased frequency of chromatid breaks was observed in both parents. </p><p><strong><em>Heterozygosity</em></strong></p><p>
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Cheung and Ewens (2006) found 520 genes with expression levels that differed significantly (p less than 0.001) between heterozygous NBS mutation carriers and controls. By linear discrimination analysis, they identified a combination of 16 genes that allowed 100% correct classification of individuals as either carriers or noncarriers. Cheung and Ewens (2006) concluded that NBS carriers have a specific gene expression phenotype, and suggested that heterozygous mutations can contribute significantly to natural variation in gene expression. </p>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p>Some of the patients studied by Saar et al. (1997) were Germans in whom the Berlin breakage syndrome had been described and others were Slavic patients in whom the Seemanova syndrome (a synonym for NBS) had been described. Saar et al. (1997) noted that it would be interesting to investigate whether Dutch patients also showed an allelic association at D8S1811, similar to what they had found in Slavic and German patients. In the first half of the 17th century, after the battle of Weissenberg in the Thirty Years War, a considerable number of Bohemian Protestants emigrated to the Netherlands from an area presently part of Poland and the Czech Republic. A major NBS mutation may have found its way to the Netherlands by migration. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Carney, J. P., Maser, R. S., Olivares, H., Davis, E. M., Le Beau, M., Yates, J. R., III, Hays, L., Morgan, W. F., Petrini, J. H. J.
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<strong>The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.</strong>
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Cell 93: 477-486, 1998.
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[PubMed: 9590181]
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[Full Text: https://doi.org/10.1016/s0092-8674(00)81175-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cerosaletti, K. M., Lange, E., Stringham, H. M., Weemaes, C. M. R., Smeets, D., Solder, B., Belohradsky, B. H., Taylor, A. M. R., Karnes, P., Elliott, A., Komatsu, K., Gatti, R. A., Boehnke, M., Concannon, P.
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<strong>Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.</strong>
|
|
Am. J. Hum. Genet. 63: 125-134, 1998.
|
|
|
|
|
|
[PubMed: 9634525]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301927]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cheung, V. G., Ewens, W. J.
|
|
<strong>Heterozygous carriers of Nijmegen breakage syndrome have a distinct gene expression phenotype.</strong>
|
|
Genome Res. 16: 973-979, 2006.
|
|
|
|
|
|
[PubMed: 16809669]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gr.5320706]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chrzanowska, K. H., Kleijer, W. J., Krajewska-Walasek, M., Bialecka, M., Gutkowska, A., Goryluk-Kozakiewicz, B., Michalkiewicz, J., Stachowski, J., Gregorek, H., Lyson-Wojciechowska, G., Janowicz, W., Jozwiak, S.
|
|
<strong>Eleven Polish patients with microcephaly, immunodeficiency and chromosomal instability: the Nijmegen breakage syndrome.</strong>
|
|
Am. J. Med. Genet. 57: 462-471, 1995.
|
|
|
|
|
|
[PubMed: 7545870]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320570321]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Conley, M. E., Spinner, M. B., Emanuel, B. S., Nowell, P. C., Nichols, W. W.
|
|
<strong>A chromosome breakage syndrome with profound immunodeficiency.</strong>
|
|
Blood 67: 1251-1256, 1986.
|
|
|
|
|
|
[PubMed: 2421804]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Curry, C. J. R., O'Lague, P., Tsai, J., Hutchison, H. T., Jaspers, N. G. J., Wara, D., Gatti, R. A.
|
|
<strong>AT(Fresno): a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome.</strong>
|
|
Am. J. Hum. Genet. 45: 270-275, 1989. Note: Erratum: Am. J. Hum. Genet. 45: 663 only, 1989.
|
|
|
|
|
|
[PubMed: 2491181]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Der Kaloustian, V. M., Kleijer, W., Booth, A., Auerbach, A. D., Mazer, B., Elliott, A. M., Abish, S., Usher, R., Watters, G., Vekemans, M., Eydoux, P.
|
|
<strong>Possible new variant of Nijmegen breakage syndrome.</strong>
|
|
Am. J. Med. Genet. 65: 21-26, 1996.
|
|
|
|
|
|
[PubMed: 8914736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1<21::AID-AJMG3>3.0.CO;2-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jaspers, N. G. J., Gatti, R. A., Baan, C., Linssen, P. C. M. L., Bootsma, D.
|
|
<strong>Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients.</strong>
|
|
Cytogenet. Cell Genet. 49: 259-263, 1988.
|
|
|
|
|
|
[PubMed: 3248383]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jaspers, N. G. J., Taalman, R. D. F. M., Baan, C.
|
|
<strong>Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia.</strong>
|
|
Am. J. Hum. Genet. 42: 66-73, 1988.
|
|
|
|
|
|
[PubMed: 3337113]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleier, S., Herrmann, M., Wittwer, B., Varon, R., Reis, A., Horst, J.
|
|
<strong>Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome.</strong>
|
|
Clin. Genet. 57: 384-387, 2000.
|
|
|
|
|
|
[PubMed: 10852373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2000.570509.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Komatsu, K., Matsuura, S., Tauchi, H., Endo, S., Kodama, S., Smeets, D., Weemaes, C., Oshimura, M.
|
|
<strong>The gene for Nijmegen breakage syndrome (V2) is not located on chromosome 11. (Letter)</strong>
|
|
Am. J. Hum. Genet. 58: 885-888, 1996.
|
|
|
|
|
|
[PubMed: 8644753]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maraschio, P., Peretti, D., Lambiase, S., Lo Curto, F., Caufin, D., Gargantini, L., Minoli, L., Zuffardi, O.
|
|
<strong>A new chromosome instability disorder.</strong>
|
|
Clin. Genet. 30: 353-365, 1986.
|
|
|
|
|
|
[PubMed: 3802554]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1986.tb01892.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maraschio, P., Spadoni, E., Tanzarella, C., Antoccia, A., di Masi, A., Maghnie, M., Varon, R., Demuth, I., Tiepolo, L., Danesino, C.
|
|
<strong>Genetic heterogeneity for a Nijmegen breakage-like syndrome.</strong>
|
|
Clin. Genet. 63: 283-290, 2003.
|
|
|
|
|
|
[PubMed: 12702161]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00054.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuura, S., Weemaes, C., Smeets, D., Takami, H., Kondo, N., Sakamoto, S., Yano, N., Nakamura, A., Tauchi, H., Endo, S., Oshimura, M., Komatsu, K.
|
|
<strong>Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24.</strong>
|
|
Am. J. Hum. Genet. 60: 1487-1494, 1997.
|
|
|
|
|
|
[PubMed: 9199571]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/515461]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, S., Kingston, H., Taylor, A. M. R., Byrd, P. J., Last, J. I. K., Brennan, B. M. D., Trueman, S., Kelsey, A., Taylor, G. M., Eden, O. B.
|
|
<strong>Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site.</strong>
|
|
Cancer Genet. Cytogenet. 154: 169-174, 2004.
|
|
|
|
|
|
[PubMed: 15474156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cancergencyto.2004.02.022]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saar, K., Chrzanowska, K. H., Stumm, M., Jung, M., Nurnberg, G., Wienker, T. F., Seemanova, E., Wegner, R.-D., Reis, A., Sperling, K.
|
|
<strong>The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.</strong>
|
|
Am. J. Hum. Genet. 60: 605-610, 1997.
|
|
|
|
|
|
[PubMed: 9042920]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seemanova, E., Passarge, E., Beneskova, D., Houstek, J., Kasal, P., Sevcikova, M.
|
|
<strong>Familial microcephaly with normal intelligence, immunodeficiency, and risk of lymphoreticular malignancies: a new autosomal recessive disorder.</strong>
|
|
Am. J. Med. Genet. 20: 639-648, 1985.
|
|
|
|
|
|
[PubMed: 3857858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320200410]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seemanova, E., Sperling, K., Neitzel, H., Varon, R., Hadac, J., Butova, O., Schrock, E., Seeman, P., Digweed, M.
|
|
<strong>Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability.</strong>
|
|
J. Med. Genet. 43: 218-224, 2006.
|
|
|
|
|
|
[PubMed: 16033915]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2005.035287]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sperling, K.
|
|
<strong>Analisi dell' eterogeneita nell'uomo.</strong>
|
|
Prospettive Pediat. 49: 53-66, 1983.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stumm, M., Gatti, R. A., Reis, A., Udar, N., Chrzanowska, K., Seemanova, E., Sperling, K., Wegner, R.-D.
|
|
<strong>The ataxia-telangiectasia-variant genes 1 and 2 are distinct from the ataxia-telangiectasia gene on chromosome 11q23.1. (Letter)</strong>
|
|
Am. J. Hum. Genet. 57: 960-962, 1995.
|
|
|
|
|
|
[PubMed: 7573059]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stumm, M., Sperling, K., Wegner, R.-D.
|
|
<strong>Noncomplementation of radiation-induced chromosome aberrations in ataxia-telangiectasia/ataxia-telangiectasia-variant heterodikaryons. (Letter)</strong>
|
|
Am. J. Hum. Genet. 60: 1246-1251, 1997.
|
|
|
|
|
|
[PubMed: 9150175]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taalman, R. D. F. M., Hustinx, T. W. J., Weemaes, C. M. R., Seemanova, E., Schmidt, A., Passarge, E., Scheres, J. M. J. C.
|
|
<strong>Further delineation of the Nijmegen breakage syndrome.</strong>
|
|
Am. J. Med. Genet. 32: 425-431, 1989.
|
|
|
|
|
|
[PubMed: 2786340]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320320332]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanzarella, C., Antoccia, A., Spadoni, E., di Masi, A., Pecile, V., Demori, E., Varon, R., Marseglia, G. L., Tiepolo, L., Maraschio, P.
|
|
<strong>Chromosome instability and nibrin protein variants in NBS heterozygotes.</strong>
|
|
Europ. J. Hum. Genet. 11: 297-303, 2003.
|
|
|
|
|
|
[PubMed: 12708449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200962]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Teebi, A. S., Al-Awadi, S. A., White, A. G.
|
|
<strong>Autosomal recessive nonsyndromal microcephaly with normal intelligence.</strong>
|
|
Am. J. Med. Genet. 26: 355-359, 1987.
|
|
|
|
|
|
[PubMed: 3812587]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320260214]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tekin, M., Dogu, F., Tacyildiz, N., Akar, E., Ikinciogullari, A., Ogur, G., Yavuz, G., Babacan, E., Akar, N.
|
|
<strong>657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.</strong>
|
|
Clin. Genet. 62: 84-88, 2002.
|
|
|
|
|
|
[PubMed: 12123493]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620112.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tupler, R., Marseglia, G. L., Stefanini, M., Prosperi, E., Chessa, L., Nardo, T., Marchi, A., Maraschio, P.
|
|
<strong>A variant of the Nijmegen breakage syndrome with unusual cytogenetic features and intermediate cellular radiosensitivity.</strong>
|
|
J. Med. Genet. 34: 196-202, 1997.
|
|
|
|
|
|
[PubMed: 9132489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.3.196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Burgt, I., Chrzanowska, K. H., Smeets, D., Weemaes, C.
|
|
<strong>Nijmegen breakage syndrome.</strong>
|
|
J. Med. Genet. 33: 153-156, 1996.
|
|
|
|
|
|
[PubMed: 8929954]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.33.2.153]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varon, R., Dutrannoy, V., Weikert, G., Tanzarella, C., Antoccia, A., Stockl, L., Spadoni, E., Kruger, L.-A., di Masi, A., Sperling, K., Digweed, M., Maraschio, P.
|
|
<strong>Mild Nijmegen breakage syndrome phenotype due to alternative splicing.</strong>
|
|
Hum. Molec. Genet. 15: 679-689, 2006.
|
|
|
|
|
|
[PubMed: 16415040]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi482]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K. M., Chrzanowska, K. H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P. R., Nowak, N. J., Stumm, M., Weemaes, C. M. R., Gatti, R. A., Wilson, R. K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P., Reis, A.
|
|
<strong>Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.</strong>
|
|
Cell 93: 467-476, 1998.
|
|
|
|
|
|
[PubMed: 9590180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81174-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C., van Munster, P. J. J., Bakkeren, J. A. J. M., Taalman, R. D. F. M.
|
|
<strong>A new chromosomal instability disorder: the Nijmegen breakage syndrome.</strong>
|
|
Acta Paediat. Scand. 70: 557-564, 1981.
|
|
|
|
|
|
[PubMed: 7315300]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1981.tb05740.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wegner, R.-D., Metzger, M., Hanefeld, F., Jaspers, N. G. J., Baan, C., Magdorf, K., Kunze, J., Sperling, K.
|
|
<strong>A new chromosomal instability disorder confirmed by complementation studies.</strong>
|
|
Clin. Genet. 33: 20-32, 1988.
|
|
|
|
|
|
[PubMed: 3277755]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Woods, C. G., Leversha, M., Rogers, J. G.
|
|
<strong>Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.</strong>
|
|
J. Med. Genet. 32: 301-305, 1995.
|
|
|
|
|
|
[PubMed: 7643362]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.4.301]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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|
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|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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 : 11/2/2009<br>Marla J. F. O'Neill - updated : 8/30/2006<br>Marla J. F. O'Neill - updated : 4/19/2006<br>Victor A. McKusick - updated : 1/31/2005<br>Natalie E. Krasikov - updated : 6/1/2004<br>Cassandra L. Kniffin - reorganized : 10/27/2003<br>Victor A. McKusick - updated : 5/12/2003<br>Victor A. McKusick - updated : 7/20/1998<br>Stylianos E. Antonarakis - updated : 5/29/1998<br>Victor A. McKusick - updated : 5/27/1998<br>Victor A. McKusick - updated : 6/16/1997<br>Victor A. McKusick - updated : 4/21/1997<br>Victor A. McKusick - updated : 3/13/1997<br>Iosif W. Lurie - updated : 1/6/1997
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</span>
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Victor A. McKusick : 6/4/1986
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carol : 09/29/2023<br>carol : 12/14/2022<br>carol : 01/07/2016<br>tpirozzi : 7/12/2013<br>terry : 3/14/2013<br>terry : 3/14/2013<br>terry : 4/12/2012<br>wwang : 11/5/2009<br>ckniffin : 11/2/2009<br>terry : 2/12/2009<br>wwang : 6/22/2007<br>terry : 6/21/2007<br>carol : 8/30/2006<br>carol : 8/30/2006<br>terry : 8/30/2006<br>wwang : 4/20/2006<br>terry : 4/19/2006<br>tkritzer : 2/4/2005<br>terry : 1/31/2005<br>carol : 6/1/2004<br>carol : 10/27/2003<br>ckniffin : 10/7/2003<br>carol : 5/15/2003<br>tkritzer : 5/14/2003<br>terry : 5/12/2003<br>terry : 4/28/2003<br>ckniffin : 3/11/2003<br>mgross : 7/22/1999<br>terry : 5/20/1999<br>carol : 7/21/1998<br>terry : 7/20/1998<br>carol : 6/3/1998<br>carol : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/29/1998<br>terry : 5/27/1998<br>alopez : 5/13/1998<br>mark : 11/11/1997<br>jenny : 10/24/1997<br>terry : 6/23/1997<br>terry : 6/17/1997<br>terry : 6/16/1997<br>alopez : 4/21/1997<br>alopez : 4/17/1997<br>alopez : 4/17/1997<br>terry : 4/11/1997<br>terry : 3/14/1997<br>terry : 3/13/1997<br>terry : 3/11/1997<br>jamie : 1/7/1997<br>jamie : 1/6/1997<br>mark : 4/3/1996<br>terry : 3/29/1996<br>terry : 3/29/1996<br>mark : 1/17/1996<br>terry : 1/16/1996<br>mark : 12/20/1995<br>terry : 10/30/1995<br>mark : 10/23/1995<br>mimadm : 2/19/1994<br>supermim : 3/17/1992<br>carol : 7/9/1991<br>supermim : 10/16/1990
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