2690 lines
168 KiB
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2690 lines
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Entry
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- #617661 - VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 2; VCRL2
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- OMIM
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<p>
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<span class="h4">#617661</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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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/617661"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS617660"> <strong>Phenotypic Series</strong> </a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div 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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</span>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS 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=27331&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/NBK593504/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=617661[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=521438" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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<div>
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<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>ORPHA:</strong> 521438<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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617661
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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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VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 2; VCRL2
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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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CONGENITAL NAD DEFICIENCY DISORDER 2<br />
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KYNURENINASE DEFICIENCY, COMPLETE
|
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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="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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<tr class="active">
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</tr>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/2/670?start=-3&limit=10&highlight=670">
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2q22.2
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Vertebral, cardiac, renal, and limb defects syndrome 2
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/617661"> 617661 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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KYNU
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/605197"> 605197 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/617661" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS617660" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/617661" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/617661" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p />
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
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|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
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|
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|
|
|
|
<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 <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</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 /> -
|
|
Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ears </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Low-set ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95515009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95515009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q17.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q17.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239234&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239234</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Ear,Low-Set-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Flat nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Congenital cardiac defects <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13213009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13213009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q24.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span><br /> -
|
|
Hypoplastic left heart <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62067003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62067003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q23.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q23.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152101&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152101</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004383" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004383</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004383" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004383</a>]</span><br /> -
|
|
Patent ductus arteriosus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83330001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83330001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/747.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">747.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CHEST </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> External Features </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Narrow chest <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249671009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249671009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000774" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000774</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000774" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000774</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ribs Sternum Clavicles & Scapulae </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Irregular ribs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4540005&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4540005</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Kidneys </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypoplastic kidneys <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32659003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32659003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266295&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266295</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000089</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000089</a>]</span><br /> -
|
|
Solitary kidney <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266294</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000122" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000122</a>]</span><br /> -
|
|
Chronic kidney disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/709044004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">709044004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N18.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N18.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N18" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N18</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/585" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">585</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/585.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">585.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1561643&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1561643</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012622" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012622</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012622" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012622</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Vertebral segmentation defects <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205455005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205455005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0432163&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0432163</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003422" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003422</a>]</span><br /> -
|
|
Hemivertebrae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68359008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68359008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.49" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.49</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/756.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">756.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Rhizomelic shortening <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866730&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866730</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008905" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008905</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008905" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008905</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Feet </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Talipes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398309008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398309008</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.70</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1301937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1301937</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001883" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001883</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001883" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001883</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">
|
|
|
|
- Speech delay (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229721007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229721007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241210</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased serum levels of 3-hydroxykynurenine (3HK) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4540015&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4540015</a>]</span><br /> -
|
|
Decreased serum levels of nicotinamide adenine dinucleotide (NAD) and NAD(H) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4540016&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4540016</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Two unrelated patients (one of Lebanese descent and one United States) have been reported (last curated September 2017)<br /> -
|
|
One patient died before age 6 months<br /> -
|
|
Slightly variable phenotype<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the kynureninase gene (KYNU, <a href="/entry/605197#0003">605197.0003</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Vertebral, cardiac, renal, and limb defects syndrome
|
|
- <a href="/phenotypicSeries/PS617660">PS617660</a>
|
|
- 3 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/213?start=-3&limit=10&highlight=213"> 2p21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617660"> Vertebral, cardiac, renal, and limb defects syndrome 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617660"> 617660 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604521"> HAAO </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604521"> 604521 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/670?start=-3&limit=10&highlight=670"> 2q22.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617661"> Vertebral, cardiac, renal, and limb defects syndrome 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
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<p>A number sign (#) is used with this entry because of evidence that vertebral, cardiac, renal, and limb defects syndrome-2 (VCRL2) is caused by homozygous or compound heterozygous mutation in the KYNU gene (<a href="/entry/605197">605197</a>) on chromosome 2q22.</p>
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<p>Vertebral, cardiac, renal, and limb defects syndrome-2 (VCRL2) is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and mild distal limb defects. Additional features are variable (summary by <a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a discussion of genetic heterogeneity of VCRL, see VCRL1 (<a href="/entry/617660">617660</a>).</p>
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<p><a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> reported 2 unrelated female patients, one born of consanguineous parents of Lebanese descent (family C) and the other born of unrelated parents from the United States (family D), with VCRL2. Both patients had segmentation defects predominantly affecting the thoracolumbar spine. Both had cardiac defects: patent ductus arteriosus in one patient and hypoplastic left heart in the other. Patient C had microcephaly, low-set ears, hypoplastic kidneys, rhizomelia, talipes, syndactyly, and anterior anus. She died at age 4 months of restrictive respiratory disease due to spondylocostal defects. Patient D had a narrow chest, solitary left kidney with chronic renal disease, short statue, and speech delay. Family history revealed that patient C was 1 of 13 pregnancies, 8 of which were lost in the first trimester. The birth of patient D was preceded by 2 first-trimester losses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Schule, I., Berger, U., Matysiak, U., Ruzaike, G., Stiller, B., Poul, M., Spiekerkoetter, U., Lausch, E., Grunert, S. C., Schmidts, M. <strong>A homozygous deletion of exon 5 of KYNU resulting from a maternal chromosome 2 isodisomy (UPD2) causes Catel-Manzke-syndrome/VCRL syndrome.</strong> Genes 12: 879, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34200361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34200361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34200361[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/10.3390/genes12060879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34200361">Schule et al. (2021)</a> reported a patient with VCRL2 who was clinically diagnosed with Catel-Manzke syndrome (see <a href="/entry/616145">616145</a>). She was prenatally diagnosed with shortened long bones, hypoplastic left heart syndrome, and rocker bottom feet. Postnatal ultrasound showed bilateral hypoplasia of the kidneys. Skeletal abnormalities included bilateral 4th and 5th finger clinodactyly, radial deviation, and polydactyly of the right hand. She also had hallux valgus and lumbrosacral wedge vertebrae. Psychomotor development was normal at 5 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34200361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Szot, J. O., Slavotinek, A., Chong, K., Brandau, O., Nezarati, M., Cueto-Gonzalez, A. M., Patel, M. S., Devine, W. P., Rego, S., Acyinena, A. P., Shannon, P., Myles-Reid, D., and 17 others. <strong>New cases that expand the genotypic and phenotypic spectrum of congenital NAD deficiency disorder.</strong> Hum. Mutat. 42: 862-876, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33942433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33942433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33942433[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/10.1002/humu.24211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33942433">Szot et al. (2021)</a> reported 4 unrelated probands, including 1 stillborn infant and 1 terminated pregnancy. All 4 patients had limb defects, including shortening of the upper and lower limbs, absent digits and nails of hands and feet, brachymelia, and syndactyly. Three patients had cardiac defects, including tetralogy of Fallot with absent pulmonary valve, atrial and ventricular septal defects, aortic hypoplasia, and mitral valve stenosis. These 3 patients also had dysmorphisms, including wide-spaced eyes, a short neck, microretrognathia, and a broad nose with anteverted nares. Features that were each observed in 1 patient included unilateral absent kidney, vertebral segmentation abnormalities, rib abnormalities, lung hypoplasia, tracheoesophageal fistula, microcephaly, and ventriculomegaly. The 2 patients who were liveborn had developmental delay, and 1 was diagnosed with autism at 6 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33942433" 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 VCRL2 in the families reported by <a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" 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 2 unrelated patients with VCRL2, <a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> identified homozygous truncating mutations in the KYNU gene (<a href="/entry/605197#0003">605197.0003</a>-<a href="/entry/605197#0005">605197.0005</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional expression studies showed that the mutations essentially abolished KYNU enzymatic activity. Analysis of plasma from patient D showed increased levels of the upstream metabolite 3HK and decreased levels of the downstream metabolites NAD and NAH(H). Studies in mice, which have different niacin levels compared to humans, indicated that the congenital malformations found in humans resulted from deficient NAD levels rather than increased 3HAA. <a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> noted that NAD is a cofactor with broad cellular effects, including ATP production, macromolecular biosynthesis, redox reactions, energy metabolism, DNA repair, and modulation of transcription factors, all of which play an important role in embryogenesis. <a href="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> theorized that niacin supplementation could be of benefit in such patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" 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 5-year-old girl with VCRL2 who was clinically diagnosed with Catel-Manzke syndrome, <a href="#1" class="mim-tip-reference" title="Schule, I., Berger, U., Matysiak, U., Ruzaike, G., Stiller, B., Poul, M., Spiekerkoetter, U., Lausch, E., Grunert, S. C., Schmidts, M. <strong>A homozygous deletion of exon 5 of KYNU resulting from a maternal chromosome 2 isodisomy (UPD2) causes Catel-Manzke-syndrome/VCRL syndrome.</strong> Genes 12: 879, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34200361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34200361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34200361[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/10.3390/genes12060879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34200361">Schule et al. (2021)</a> identified homozygosity for deletion of exon 5 of the KYNU gene. Exon 5 contains 62 bp (c.374_436del, NM_00119924.1) and the deletion is predicted to result in a frameshift and premature termination (p.125_145delLeu146TyrfsTer). The deletion breakpoints (chr2:142,954,376 and chr2:142,955,239, GRCh38), encompassing 835 bp (<a href="/entry/605197#0006">605197.0006</a>), were confirmed by CGH array and long-range PCR. SNP array showed that the homozygous mutation arose from maternal uniparental isodisomy of chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34200361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 unrelated patients with VCRL2, <a href="#3" class="mim-tip-reference" title="Szot, J. O., Slavotinek, A., Chong, K., Brandau, O., Nezarati, M., Cueto-Gonzalez, A. M., Patel, M. S., Devine, W. P., Rego, S., Acyinena, A. P., Shannon, P., Myles-Reid, D., and 17 others. <strong>New cases that expand the genotypic and phenotypic spectrum of congenital NAD deficiency disorder.</strong> Hum. Mutat. 42: 862-876, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33942433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33942433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33942433[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/10.1002/humu.24211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33942433">Szot et al. (2021)</a> identified compound heterozygous or homozygous mutations in the KYNU gene (see, e.g., <a href="/entry/605197#0007">605197.0007</a>-<a href="/entry/605197#0010">605197.0010</a>). Yeast with a homozygous knockout for bna5, the yeast ortholog of human KYNU, were transformed with plasmids containing KYNU with each of the mutations or with wildtype KYNU. Transfection with each of 4 mutant KYNU plasmids resulted in smaller yeast mass compared to wildtype when grown in niacin-free culture media. NAD levels were reduced in the yeast transformed with any of the 6 mutant KYNU plasmids compared to wildtype. <a href="#3" class="mim-tip-reference" title="Szot, J. O., Slavotinek, A., Chong, K., Brandau, O., Nezarati, M., Cueto-Gonzalez, A. M., Patel, M. S., Devine, W. P., Rego, S., Acyinena, A. P., Shannon, P., Myles-Reid, D., and 17 others. <strong>New cases that expand the genotypic and phenotypic spectrum of congenital NAD deficiency disorder.</strong> Hum. Mutat. 42: 862-876, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33942433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33942433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33942433[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/10.1002/humu.24211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33942433">Szot et al. (2021)</a> concluded that the compromised growth and/or NAD content of the bna5 knockout yeast transfected with each mutant KYNU was a result of impaired KYNU function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33942433" 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="#2" class="mim-tip-reference" title="Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others. <strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong> New Eng. J. Med. 377: 544-552, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>] [<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28792876">Shi et al. (2017)</a> found that Kynu-null mice were viable and normal. Plasma analysis showed increased 3HK levels, but normal NAD levels. The authors noted that mice have increased niacin levels compared to humans and that mouse embryos may receive niacin from their mothers, resulting in a buffering effect on genetic-based NAD deficiency. These findings suggested that the congenital malformations found in humans with increased 3HK levels and decreased levels of NAD resulted from the deficient NAD levels. Indeed, further studies in mutant mice born to mothers on a niacin-free diet showed that NAD deficiency due to lack of Kynu resulted in multiple defects, including defects in vertebral segmentation, heart defects, small kidney, cleft palate, talipes, syndactyly, and caudal agenesis. Supplementation of Kynu-null mouse embryos with niacin during gestation restored NAD levels and prevented the disruption of embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Schule2021" class="mim-anchor"></a>
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Schule, I., Berger, U., Matysiak, U., Ruzaike, G., Stiller, B., Poul, M., Spiekerkoetter, U., Lausch, E., Grunert, S. C., Schmidts, M.
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<strong>A homozygous deletion of exon 5 of KYNU resulting from a maternal chromosome 2 isodisomy (UPD2) causes Catel-Manzke-syndrome/VCRL syndrome.</strong>
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Genes 12: 879, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34200361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34200361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34200361[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=34200361" 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/10.3390/genes12060879" target="_blank">Full Text</a>]
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Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others.
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<strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong>
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New Eng. J. Med. 377: 544-552, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28792876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28792876</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28792876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1616361" target="_blank">Full Text</a>]
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<a id="Szot2021" class="mim-anchor"></a>
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Szot, J. O., Slavotinek, A., Chong, K., Brandau, O., Nezarati, M., Cueto-Gonzalez, A. M., Patel, M. S., Devine, W. P., Rego, S., Acyinena, A. P., Shannon, P., Myles-Reid, D., and 17 others.
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<strong>New cases that expand the genotypic and phenotypic spectrum of congenital NAD deficiency disorder.</strong>
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Hum. Mutat. 42: 862-876, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33942433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33942433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33942433[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=33942433" 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/humu.24211" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 07/18/2022
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Hilary J. Vernon - updated : 07/11/2022
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Cassandra L. Kniffin : 09/07/2017
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carol : 02/08/2024
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carol : 07/18/2022<br>carol : 07/11/2022<br>joanna : 10/30/2017<br>carol : 09/26/2017<br>carol : 09/25/2017<br>carol : 09/21/2017<br>carol : 09/21/2017<br>ckniffin : 09/20/2017
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<strong>#</strong> 617661
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VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 2; VCRL2
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CONGENITAL NAD DEFICIENCY DISORDER 2<br />
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KYNURENINASE DEFICIENCY, COMPLETE
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<strong>ORPHA:</strong> 521438;
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Inheritance
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2q22.2
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Vertebral, cardiac, renal, and limb defects syndrome 2
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617661
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Autosomal recessive
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3
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KYNU
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605197
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<p>A number sign (#) is used with this entry because of evidence that vertebral, cardiac, renal, and limb defects syndrome-2 (VCRL2) is caused by homozygous or compound heterozygous mutation in the KYNU gene (605197) on chromosome 2q22.</p>
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<strong>Description</strong>
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<p>Vertebral, cardiac, renal, and limb defects syndrome-2 (VCRL2) is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and mild distal limb defects. Additional features are variable (summary by Shi et al., 2017). </p><p>For a discussion of genetic heterogeneity of VCRL, see VCRL1 (617660).</p>
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<strong>Clinical Features</strong>
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<p>Shi et al. (2017) reported 2 unrelated female patients, one born of consanguineous parents of Lebanese descent (family C) and the other born of unrelated parents from the United States (family D), with VCRL2. Both patients had segmentation defects predominantly affecting the thoracolumbar spine. Both had cardiac defects: patent ductus arteriosus in one patient and hypoplastic left heart in the other. Patient C had microcephaly, low-set ears, hypoplastic kidneys, rhizomelia, talipes, syndactyly, and anterior anus. She died at age 4 months of restrictive respiratory disease due to spondylocostal defects. Patient D had a narrow chest, solitary left kidney with chronic renal disease, short statue, and speech delay. Family history revealed that patient C was 1 of 13 pregnancies, 8 of which were lost in the first trimester. The birth of patient D was preceded by 2 first-trimester losses. </p><p>Schule et al. (2021) reported a patient with VCRL2 who was clinically diagnosed with Catel-Manzke syndrome (see 616145). She was prenatally diagnosed with shortened long bones, hypoplastic left heart syndrome, and rocker bottom feet. Postnatal ultrasound showed bilateral hypoplasia of the kidneys. Skeletal abnormalities included bilateral 4th and 5th finger clinodactyly, radial deviation, and polydactyly of the right hand. She also had hallux valgus and lumbrosacral wedge vertebrae. Psychomotor development was normal at 5 years of age. </p><p>Szot et al. (2021) reported 4 unrelated probands, including 1 stillborn infant and 1 terminated pregnancy. All 4 patients had limb defects, including shortening of the upper and lower limbs, absent digits and nails of hands and feet, brachymelia, and syndactyly. Three patients had cardiac defects, including tetralogy of Fallot with absent pulmonary valve, atrial and ventricular septal defects, aortic hypoplasia, and mitral valve stenosis. These 3 patients also had dysmorphisms, including wide-spaced eyes, a short neck, microretrognathia, and a broad nose with anteverted nares. Features that were each observed in 1 patient included unilateral absent kidney, vertebral segmentation abnormalities, rib abnormalities, lung hypoplasia, tracheoesophageal fistula, microcephaly, and ventriculomegaly. The 2 patients who were liveborn had developmental delay, and 1 was diagnosed with autism at 6 years of age. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of VCRL2 in the families reported by Shi et al. (2017) was consistent with autosomal recessive inheritance. </p>
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<p>In 2 unrelated patients with VCRL2, Shi et al. (2017) identified homozygous truncating mutations in the KYNU gene (605197.0003-605197.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional expression studies showed that the mutations essentially abolished KYNU enzymatic activity. Analysis of plasma from patient D showed increased levels of the upstream metabolite 3HK and decreased levels of the downstream metabolites NAD and NAH(H). Studies in mice, which have different niacin levels compared to humans, indicated that the congenital malformations found in humans resulted from deficient NAD levels rather than increased 3HAA. Shi et al. (2017) noted that NAD is a cofactor with broad cellular effects, including ATP production, macromolecular biosynthesis, redox reactions, energy metabolism, DNA repair, and modulation of transcription factors, all of which play an important role in embryogenesis. Shi et al. (2017) theorized that niacin supplementation could be of benefit in such patients. </p><p>In a 5-year-old girl with VCRL2 who was clinically diagnosed with Catel-Manzke syndrome, Schule et al. (2021) identified homozygosity for deletion of exon 5 of the KYNU gene. Exon 5 contains 62 bp (c.374_436del, NM_00119924.1) and the deletion is predicted to result in a frameshift and premature termination (p.125_145delLeu146TyrfsTer). The deletion breakpoints (chr2:142,954,376 and chr2:142,955,239, GRCh38), encompassing 835 bp (605197.0006), were confirmed by CGH array and long-range PCR. SNP array showed that the homozygous mutation arose from maternal uniparental isodisomy of chromosome 2. </p><p>In 4 unrelated patients with VCRL2, Szot et al. (2021) identified compound heterozygous or homozygous mutations in the KYNU gene (see, e.g., 605197.0007-605197.0010). Yeast with a homozygous knockout for bna5, the yeast ortholog of human KYNU, were transformed with plasmids containing KYNU with each of the mutations or with wildtype KYNU. Transfection with each of 4 mutant KYNU plasmids resulted in smaller yeast mass compared to wildtype when grown in niacin-free culture media. NAD levels were reduced in the yeast transformed with any of the 6 mutant KYNU plasmids compared to wildtype. Szot et al. (2021) concluded that the compromised growth and/or NAD content of the bna5 knockout yeast transfected with each mutant KYNU was a result of impaired KYNU function. </p>
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<p>Shi et al. (2017) found that Kynu-null mice were viable and normal. Plasma analysis showed increased 3HK levels, but normal NAD levels. The authors noted that mice have increased niacin levels compared to humans and that mouse embryos may receive niacin from their mothers, resulting in a buffering effect on genetic-based NAD deficiency. These findings suggested that the congenital malformations found in humans with increased 3HK levels and decreased levels of NAD resulted from the deficient NAD levels. Indeed, further studies in mutant mice born to mothers on a niacin-free diet showed that NAD deficiency due to lack of Kynu resulted in multiple defects, including defects in vertebral segmentation, heart defects, small kidney, cleft palate, talipes, syndactyly, and caudal agenesis. Supplementation of Kynu-null mouse embryos with niacin during gestation restored NAD levels and prevented the disruption of embryogenesis. </p>
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<strong>REFERENCES</strong>
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Schule, I., Berger, U., Matysiak, U., Ruzaike, G., Stiller, B., Poul, M., Spiekerkoetter, U., Lausch, E., Grunert, S. C., Schmidts, M.
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<strong>A homozygous deletion of exon 5 of KYNU resulting from a maternal chromosome 2 isodisomy (UPD2) causes Catel-Manzke-syndrome/VCRL syndrome.</strong>
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Genes 12: 879, 2021.
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[PubMed: 34200361]
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[Full Text: https://doi.org/10.3390/genes12060879]
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Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., and 21 others.
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<strong>NAD deficiency, congenital malformations, and niacin supplementation.</strong>
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New Eng. J. Med. 377: 544-552, 2017.
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[PubMed: 28792876]
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[Full Text: https://doi.org/10.1056/NEJMoa1616361]
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Szot, J. O., Slavotinek, A., Chong, K., Brandau, O., Nezarati, M., Cueto-Gonzalez, A. M., Patel, M. S., Devine, W. P., Rego, S., Acyinena, A. P., Shannon, P., Myles-Reid, D., and 17 others.
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<strong>New cases that expand the genotypic and phenotypic spectrum of congenital NAD deficiency disorder.</strong>
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Hum. Mutat. 42: 862-876, 2021.
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[PubMed: 33942433]
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[Full Text: https://doi.org/10.1002/humu.24211]
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Hilary J. Vernon - updated : 07/18/2022<br>Hilary J. Vernon - updated : 07/11/2022
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