4278 lines
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Entry
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- *609019 - BIOTINIDASE; BTD
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*609019</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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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="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</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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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609019">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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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 class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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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>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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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="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000169814;t=ENST00000643237" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=686" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=609019" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<div id="mimDnaLinksFold" 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.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000169814;t=ENST00000643237" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001281723,NM_001281724,NM_001281725,NM_001281726,NM_001323582,NM_001370658,NM_001370752,NM_001370753,NM_001407364,NM_001407365,NM_001407366,NM_001407367,NM_001407368,NM_001407369,NM_001407370,NM_001407371,NM_001407372,NM_001407373,NM_001407374,NM_001407375,NM_001407376,NM_001407377,NM_001407378,NM_001407379,NM_001407380,NM_001407381,NM_001407382,NM_001407383,NM_001407384,NM_001407386,NM_001407388,NM_001407390,NM_001407392,NM_001407394,NM_001407395,NM_001407396,NM_001407397,NM_001407398,NM_001407399,NM_001407400,NM_001407401,NR_176358,NR_176359" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001370658" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=609019" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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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="mimProteinLinksFold" 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://hprd.org/summary?hprd_id=08359&isoform_id=08359_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/BTD" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/468824,2674075,15082373,119584658,119584659,119584660,189053810,194376872,194384802,221043776,226693503,440575757,528524486,1042812835,1654854340,1669945746,1669946503,1674301254,1674557681,1832253308,2247445824,2247445830,2247445834,2247445840,2247445842,2247445844,2247445875,2247445881,2247445883,2247445894,2247445900,2247445911,2247445913,2247445915,2247445917,2247445919,2247445924,2247445926,2247445928,2247445932,2247445942,2247445948,2247445960,2247445968,2247445972,2247445976,2247445978,2247445980,2247445985,2247445987,2247445989,2247446012,2247446017" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P43251" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" 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="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</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="mimGeneInfoLinksFold" 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="http://biogps.org/#goto=genereport&id=686" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000169814;t=ENST00000643237" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=BTD" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=BTD" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+686" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/BTD" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:686" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/686" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr3&hgg_gene=ENST00000643237.3&hgg_start=15601361&hgg_end=15722516&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="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="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="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse 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://search.clinicalgenome.org/kb/gene-dosage/HGNC:1122" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1122" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/btd" 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=609019[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>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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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="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=609019[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000169814" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=BTD" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=BTD" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BTD" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.arup.utah.edu/database/BTD/BTD_welcome.php" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=BTD&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA25443" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:1122" 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="https://flybase.org/reports/FBgn0029848.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1347001" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/BTD#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1347001" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/686/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=686" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060825-186" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" 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="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</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="mimCellularPathwaysLinksFold" 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.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:686" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=BTD&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</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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<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> 8808004<br />
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<strong>ICD10CM:</strong> D81.810<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="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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609019
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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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BIOTINIDASE; BTD
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=BTD" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">BTD</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/3/97?start=-3&limit=10&highlight=97">3p25.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:15601361-15722516&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">3:15,601,361-15,722,516</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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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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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/3/97?start=-3&limit=10&highlight=97">
|
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3p25.1
|
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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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Biotinidase deficiency
|
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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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|
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<a href="/entry/253260"> 253260 </a>
|
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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">
|
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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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</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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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/609019" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/609019" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</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>
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<p>Serum biotinidase (BTD; <a href="https://enzyme.expasy.org/EC/3.5.1.12" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.5.1.12</a>) catalyzes the hydrolysis of biocytin, a normal product of biotin-dependent carboxylase degradation, to biotin and lysine. The process results in the regeneration of free biotin. Biotin is an essential water-soluble vitamin and is the coenzyme for 4 carboxylases necessary for normal metabolism in humans: pyruvate carboxylase (PCC; <a href="/entry/608786">608786</a>), propionyl-CoA carboxylase (PCCA; <a href="/entry/232000">232000</a>), alpha-methylcrotonyl-CoA carboxylase (see MCCC1; <a href="/entry/609010">609010</a>), and acetyl-CoA carboxylase (ACACA; <a href="/entry/200350">200350</a>) (summary by <a href="#3" class="mim-tip-reference" title="Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B. <strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong> J. Biol. Chem. 269: 6566-6570, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509806</a>]" pmid="7509806">Cole et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7509806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Pomponio, R. J., Hymes, J., Reynolds, T. R., Meyers, G. A., Fleischhauer, K., Buck, G. A., Wolf, B. <strong>Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis.</strong> Pediat. Res. 42: 840-848, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9396567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9396567</a>] [<a href="https://doi.org/10.1203/00006450-199712000-00020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9396567">Pomponio et al. (1997)</a> stated that biotinidase has also been shown to have biotinyl-transferase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9396567" 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="#3" class="mim-tip-reference" title="Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B. <strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong> J. Biol. Chem. 269: 6566-6570, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509806</a>]" pmid="7509806">Cole et al. (1994)</a> cloned and sequenced a cDNA corresponding to the BTD gene from a human hepatic cDNA library. The deduced 543-amino acid protein has a molecular mass of approximately 57 kD and contains 6 potential N-linked glycosylation sites. Northern blot analysis detected BTD mRNA in human heart, brain, placenta, liver, lung, skeletal muscle, kidney, and pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7509806" 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="#7" class="mim-tip-reference" title="Knight, H. C., Reynolds, T. R., Meyers, G. A., Pomponio, R. J., Buck, G. A., Wolf, B. <strong>Structure of the human biotinidase gene.</strong> Mammalian Genome 9: 327-330, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9530634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9530634</a>] [<a href="https://doi.org/10.1007/s003359900760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9530634">Knight et al. (1998)</a> determined that the BTD gene contains 4 exons and spans at least 23 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9530634" 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>Using fluorescence in situ hybridization, <a href="#4" class="mim-tip-reference" title="Cole, H., Weremowicz, S., Morton, C. C., Wolf, B. <strong>Localization of serum biotinidase (BTD) to human chromosome 3 in band p25.</strong> Genomics 22: 662-663, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001986</a>] [<a href="https://doi.org/10.1006/geno.1994.1449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001986">Cole et al. (1994)</a> mapped the BTD gene to chromosome 3p25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001986" 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 10 of 25 patients with biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#14" class="mim-tip-reference" title="Pomponio, R. J., Reynolds, T. R., Cole, H., Buck, G. A., Wolf, B. <strong>Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency.</strong> Nature Genet. 11: 96-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550325</a>] [<a href="https://doi.org/10.1038/ng0995-96" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550325">Pomponio et al. (1995)</a> identified an allele with a 7-bp deletion and a 3-bp insertion in the BTD gene (<a href="#0001">609019.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550325" 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 37 symptomatic children (30 index cases and 7 sibs) with profound biotinidase deficiency, <a href="#11" class="mim-tip-reference" title="Pomponio, R. J., Hymes, J., Reynolds, T. R., Meyers, G. A., Fleischhauer, K., Buck, G. A., Wolf, B. <strong>Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis.</strong> Pediat. Res. 42: 840-848, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9396567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9396567</a>] [<a href="https://doi.org/10.1203/00006450-199712000-00020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9396567">Pomponio et al. (1997)</a> identified 21 mutations in the BTD gene. The 2 most common mutations were the del7/ins3 mutation and R538C (<a href="#0003">609019.0003</a>); these 2 mutations were found in 31 of 60 alleles (52%), whereas the remainder of the alleles were accounted for by the 19 other unique mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9396567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated asymptomatic adults with biotinidase deficiency who were diagnosed because their children were identified by newborn screening, <a href="#18" class="mim-tip-reference" title="Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J. <strong>Profound biotinidase deficiency in two asymptomatic adults.</strong> Am. J. Med. Genet. 73: 5-9, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375914">Wolf et al. (1997)</a> found homozygous mutations in the BTD gene (<a href="#0005">609019.0005</a> and <a href="#0006">609019.0006</a>). <a href="#18" class="mim-tip-reference" title="Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J. <strong>Profound biotinidase deficiency in two asymptomatic adults.</strong> Am. J. Med. Genet. 73: 5-9, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375914">Wolf et al. (1997)</a> concluded that epigenetic factors may protect some enzyme-deficient individuals from developing symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9375914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B. <strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong> J. Inherit. Metab. Dis. 23: 120-128, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801053</a>] [<a href="https://doi.org/10.1023/a:1005609614443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10801053">Pomponio et al. (2000)</a> identified mutations in the BTD gene (see, e.g., <a href="#0007">609019.0007</a>; <a href="#0010">609019.0010</a>; <a href="#0011">609019.0011</a>) in Turkish children with biotinidase deficiency identified both clinically and by newborn screening. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B. <strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong> Am. J. Med. Genet. 179A: 978-982, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30912303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30912303</a>] [<a href="https://doi.org/10.1002/ajmg.a.61137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30912303">Carvalho et al. (2019)</a> reported molecular and serum enzyme testing results in 14 Brazilian children with biotinidase deficiency who were identified by newborn screening. Nine novel mutations were identified, including 2 deletions and 7 missense mutations. Seven of the mutations were found in exon 4, which encodes the C terminus. Among the missense mutations that were identified in homozygous state, F361V (<a href="#0012">609019.0012</a>) led to partial biotinidase deficiency in 2 unrelated patients, and A534V (<a href="#0013">609019.0013</a>) led to profound biotinidase deficiency in 1 patient. The previously reported D444H mutation (<a href="#0005">609019.0005</a>) was found in compound heterozygosity in 7 patients; 5 of the patients had partial biotinidase deficiency, including one with compound heterozygosity for A534V and one with compound heterozygosity for F361V, and 2 of the patients had possible partial biotinidase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30912303" 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="#6" class="mim-tip-reference" title="Hernandez-Vazquez, A., Wolf, B., Pindolia, K., Ortega-Cuellar, D., Hernandez-Gonzalez, R., Heredia-Antunez, A., Ibarra-Gonzalez, I., Velazquez-Arellano, A. <strong>Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.</strong> Molec. Genet. Metab. 110: 248-254, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24075304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24075304</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.08.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24075304">Hernandez-Vazquez et al. (2013)</a> studied the metabolic features of 3-week-old Btd-null mice that had been fed a biotin-deficient diet for 5 days. The mice showed no phenotypic alterations characteristic of biotinidase deficiency, such as seizures, hypotonia, ataxia, or hair or skin abnormalities. Liver samples from the mice showed decreased cellular energy, with an increase in the AMP/ATP ratio and an increase in phosphorylation of AMP-activated protein kinase (AMPK; see <a href="/entry/602739">602739</a>). There was inhibition of the signaling protein mTOR (<a href="/entry/601231">601231</a>), which is a driver of protein synthesis and growth. The transcripts of several central carbon metabolism genes were also changed: GCK (<a href="/entry/138079">138079</a>) and FASN (<a href="/entry/600212">600212</a>) were increased, whereas those of PCK1 (<a href="/entry/614168">614168</a>) and CPT1 (<a href="/entry/600528">600528</a>) were decreased. The mice also showed increased serum levels of free fatty acids, decreased levels of blood glucose, and increased insulin sensitivity. These findings indicated a severe energy deficit and altered energy metabolism in the absence of adequate biotin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24075304" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=609019[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 BIOTINIDASE DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80338684 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338684;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001972 OR RCV000078084" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001972, RCV000078084" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001972...</a>
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<p>In 10 of 25 patients with biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#14" class="mim-tip-reference" title="Pomponio, R. J., Reynolds, T. R., Cole, H., Buck, G. A., Wolf, B. <strong>Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency.</strong> Nature Genet. 11: 96-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550325</a>] [<a href="https://doi.org/10.1038/ng0995-96" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550325">Pomponio et al. (1995)</a> identified an allele with a 7-bp deletion and a 3-bp insertion (98-104del7ins3), immediately 3-prime to a 12-bp polypyrimidine sequence in the BTD gene. The deletion/insertion resulted in a frameshift that was predicted to terminate with a stop codon at amino acid 68, resulting in a truncated protein with an amino acid sequence different from that of biotinidase; the other allele contained the normal sequence. Three other patients were homozygous for the mutation. These 3 patients lacked crossreacting material to antibodies prepared against normal human serum biotinidase. The parents of 1 of the 3 patients were first cousins and those of a second were third cousins, whereas the parents of the third patient were not consanguineous. Racial and ethnic diversity and worldwide distribution of the patients studied suggested that the relatively high frequency of the mutation did not arise through a founder effect, and the authors suggested that it was a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550325" 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="Gordon, A. <strong>Biotinidase mutational 'hotspot'. (Letter)</strong> Nature Genet. 13: 144-145, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640218</a>] [<a href="https://doi.org/10.1038/ng0696-144b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640218">Gordon (1996)</a>, who referred to the mutation as arising through an indel (insertion/deletion) event, questioned the 'hotspot' hypothesis and suggested that, like the delF508 mutation (<a href="/entry/219700#0001">219700.0001</a>) for cystic fibrosis, this may be a very ancient mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640218" 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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<a id="0002" class="mim-anchor"></a>
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<strong>.0002 BIOTINIDASE DEFICIENCY</strong>
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</h4>
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BTD, 15-BP DEL/11-BP INS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs672601248 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs672601248;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs672601248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs672601248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000169138 OR RCV000728443" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169138, RCV000728443" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169138...</a>
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<p>In a child with profound biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#12" class="mim-tip-reference" title="Pomponio, R. J., Narasimhan, V., Reynolds, T. R., Buck, G. A., Povirk, L. F., Wolf, B. <strong>Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure.</strong> Hum. Molec. Genet. 5: 1657-1661, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894703</a>] [<a href="https://doi.org/10.1093/hmg/5.10.1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8894703">Pomponio et al. (1996)</a> identified homozygosity for a 15-bp deletion/11-bp insertion mutation within exon D (nucleotides 1059-1359 of the sequence reported by <a href="#3" class="mim-tip-reference" title="Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B. <strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong> J. Biol. Chem. 269: 6566-6570, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509806</a>]" pmid="7509806">Cole et al. (1994)</a>) of the BTD gene. The mutation resulted in a frameshift predicted to terminate the polypeptide prematurely. The authors proposed 2 possible mechanisms to account for this mutation, both of which involved formation of a quasipalindromic structure in the replicating DNA strands. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8894703+7509806" 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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<a id="0003" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0003 BIOTINIDASE DEFICIENCY</strong>
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BTD, ARG538CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338686 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338686;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338686?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001975 OR RCV000790794 OR RCV003242960 OR RCV003421895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001975, RCV000790794, RCV003242960, RCV003421895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001975...</a>
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<p>In 10 of 30 symptomatic children with profound biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#13" class="mim-tip-reference" title="Pomponio, R. J., Norrgard, K. J., Hymes, J., Reynolds, T. R., Buck, G. A., Baumgartner, R., Suormala, T., Wolf, B. <strong>Arg538 to cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children.</strong> Hum. Genet. 99: 506-512, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099842</a>] [<a href="https://doi.org/10.1007/s004390050397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9099842">Pomponio et al. (1997)</a> identified a 1612C-T transition in a CpG dinucleotide in exon D of the BTD gene, resulting in an arg538-to-cys (R538C) substitution. Five of the patients were compound heterozygous for this mutation and a deletion/insertion mutation (<a href="#0001">609019.0001</a>). There was no detectable biotinidase protein in sera of homozygous children, and the authors suggested that the R538C mutation results in abnormal disulfide bond formation, rapid degradation of the aberrant enzyme, and failure to secrete the mutant enzyme from the cells into the blood. <a href="#13" class="mim-tip-reference" title="Pomponio, R. J., Norrgard, K. J., Hymes, J., Reynolds, T. R., Buck, G. A., Baumgartner, R., Suormala, T., Wolf, B. <strong>Arg538 to cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children.</strong> Hum. Genet. 99: 506-512, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099842</a>] [<a href="https://doi.org/10.1007/s004390050397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9099842">Pomponio et al. (1997)</a> reported that the R538C mutation is the second most common mutation causing biotinidase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9099842" 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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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 BIOTINIDASE DEFICIENCY</strong>
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</h4>
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BTD, GLY34SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs119103232 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103232;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs119103232?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs119103232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs119103232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001976 OR RCV004751191" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001976, RCV004751191" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001976...</a>
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<p>In 2 unrelated individuals with profound biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#15" class="mim-tip-reference" title="Pomponio, R. J., Reynolds, T. R., Mandel, H., Admoni, O., Melone, P. D., Buck, G. A., Wolf, B. <strong>Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3-prime splice acceptor site within an exon of the human biotinidase gene.</strong> Hum. Molec. Genet. 6: 739-745, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158148</a>] [<a href="https://doi.org/10.1093/hmg/6.5.739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158148">Pomponio et al. (1997)</a> identified a 100G-A transition in the BTD gene, located 57 bases downstream of the authentic splice acceptor site in exon B, resulting in a gly34-to-ser (G34S) substitution. The transition also generated a 3-prime splice acceptor site. The sequence of the PCR-amplified cDNA from the homozygous child revealed that all the product was shorter than that of normal individuals and was the result of aberrant splicing. The aberrantly spliced transcript lacks 57 nucleotides, including a second in-frame ATG, that encode most of the putative signal peptide and results in an in-frame deletion of 19 amino acids. The mutation resulted in failure to secrete the aberrant protein into the blood. This was the first reported example in which a point mutation creates a cryptic 3-prime splice acceptor site motif that is used preferentially over the upstream authentic splice site. <a href="#15" class="mim-tip-reference" title="Pomponio, R. J., Reynolds, T. R., Mandel, H., Admoni, O., Melone, P. D., Buck, G. A., Wolf, B. <strong>Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3-prime splice acceptor site within an exon of the human biotinidase gene.</strong> Hum. Molec. Genet. 6: 739-745, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158148</a>] [<a href="https://doi.org/10.1093/hmg/6.5.739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158148">Pomponio et al. (1997)</a> stated that preferential usage of the downstream splice site was not consistent with the 5-prime-to-3-prime scanning model of RNA splicing, but was consistent with the exon definition model. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158148" 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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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 BIOTINIDASE DEFICIENCY</strong>
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BTD, ALA171THR AND ASP444HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs13073139 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs13073139;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs13073139?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs13073139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs13073139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs13078881 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs13078881;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs13078881?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs13078881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs13078881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an asymptomatic man with biotinidase deficiency (<a href="/entry/253260">253260</a>) who was diagnosed because his affected child was identified by newborn screening, <a href="#18" class="mim-tip-reference" title="Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J. <strong>Profound biotinidase deficiency in two asymptomatic adults.</strong> Am. J. Med. Genet. 73: 5-9, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375914">Wolf et al. (1997)</a> identified a homozygous allelic double missense mutation in the BTD gene: a 511G-A transition, resulting in an ala171-to-thr (A171T) substitution, which had been described by <a href="#3" class="mim-tip-reference" title="Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B. <strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong> J. Biol. Chem. 269: 6566-6570, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509806</a>]" pmid="7509806">Cole et al. (1994)</a>, and a 1330G-C transversion, resulting in an asp444-to-his (D444H) substitution, which had been described by <a href="#9" class="mim-tip-reference" title="Norrgard, K. J., Swango, K. L., Wolf, B. <strong>Mutation (D444H) in the biotinidase gene causes approximately 50% loss of enzyme activity and is common in the general population. (Abstract)</strong> Am. J. Hum. Genet. 59 (suppl.): A275 only, 1996."None>Norrgard et al. (1996)</a>. The daughter had the same genotype; the parents of the father and his wife were heterozygous for this doubly mutant allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7509806+9375914" 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="#17" class="mim-tip-reference" title="Swango, K. L., Demirkol, M., Huner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., Wolf, B. <strong>Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.</strong> Hum. Genet. 102: 571-575, 1998. Note: Erratum: Hum. Genet. 102: 712 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9654207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9654207</a>] [<a href="https://doi.org/10.1007/s004390050742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9654207">Swango et al. (1998)</a> found that 18 of 19 randomly selected individuals with partial biotinidase deficiency (10 to 30% activity) were heterozygous for the D444H mutation. Previous studies had indicated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. <a href="#17" class="mim-tip-reference" title="Swango, K. L., Demirkol, M., Huner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., Wolf, B. <strong>Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.</strong> Hum. Genet. 102: 571-575, 1998. Note: Erratum: Hum. Genet. 102: 712 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9654207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9654207</a>] [<a href="https://doi.org/10.1007/s004390050742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9654207">Swango et al. (1998)</a> compared the D444H mutation to the Duarte variant of galactosemia (<a href="/entry/230400#0005">230400.0005</a>). The D444H mutation in 1 allele in combination with a mutation for profound deficiency in the other allele is a common cause of partial biotinidase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9654207" 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="Norrgard, K. J., Pomponio, R. J., Hymes, J., Wolf, B. <strong>Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.</strong> Pediat. Res. 46: 20-27, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400129</a>] [<a href="https://doi.org/10.1203/00006450-199907000-00004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400129">Norrgard et al. (1999)</a> found the double mutation (A171T/D444H) to be the second most common allele identified by newborn screening, appearing in 17.3% of alleles. They observed a second double mutation (F403V/D444H); see <a href="#0009">609019.0009</a>. It was unknown whether A171T or F403V must act in concert with D444H to produce profound biotinyl-hydrolase and -transferase deficiencies. Either the A171T or the F403V mutation alone could produce a nonfunctional enzyme, although neither had been observed alone. Although A171T/D444H was very frequent in newborn screening alleles, it was found in none of the patients whose disorder had been detected on the basis of symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400129" 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 preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, <a href="#1" class="mim-tip-reference" title="Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F. <strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong> Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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/10.1126/scitranslmed.3001756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21228398">Bell et al. (2011)</a> found that the D444H mutation in BTD is a polymorphism carried by asymptomatic individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21228398" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28934601 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28934601;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28934601?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28934601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28934601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001978 OR RCV000445043" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001978, RCV000445043" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001978...</a>
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<p>In an asymptomatic woman with biotinidase deficiency (<a href="/entry/253260">253260</a>) who was diagnosed after her child was identified by newborn screening, <a href="#18" class="mim-tip-reference" title="Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J. <strong>Profound biotinidase deficiency in two asymptomatic adults.</strong> Am. J. Med. Genet. 73: 5-9, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375914">Wolf et al. (1997)</a> identified a homozygous 755A-G transition, resulting in an asp252-to-gly (D252G) substitution. Her parents were heterozygous for the mutation. Her husband was heterozygous for a missense mutation (Q456H; <a href="#0007">609019.0007</a>). The enzyme-deficient daughter was a compound heterozygote for the mutations found in the mother and father. The son, who was identified through newborn screening, was presumably also a compound heterozygote for these 2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9375914" 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="#18" class="mim-tip-reference" title="Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J. <strong>Profound biotinidase deficiency in two asymptomatic adults.</strong> Am. J. Med. Genet. 73: 5-9, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375914">Wolf et al. (1997)</a> identified a heterozygous 1368A-C transversion in the BTD gene, resulting in a gln456-to-his (Q456H) substitution (originally published as GLN556HIS) in a man whose child was diagnosed with biotinidase deficiency (<a href="/entry/253260">253260</a>). The affected child was compound heterozygous for the Q456H mutation and D252G (<a href="#0006">609019.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9375914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B. <strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong> J. Inherit. Metab. Dis. 23: 120-128, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801053</a>] [<a href="https://doi.org/10.1023/a:1005609614443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10801053">Pomponio et al. (2000)</a> identified homozygosity for the Q456H mutation in a clinically ascertained child in the Turkish population. They also identified the Q456H mutation in homozygosity or compound heterozygosity in 2 Turkish children ascertained by newborn screening. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801053" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893692 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893692;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893692?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001980 OR RCV002272006 OR RCV003230341" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001980, RCV002272006, RCV003230341" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001980...</a>
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<p>In a Japanese child with biotinidase deficiency (<a href="/entry/253260">253260</a>) identified in a pilot newborn screening program in Sapporo, Japan, <a href="#16" class="mim-tip-reference" title="Pomponio, R. J., Yamaguchi, A., Arashima, S., Hymes, J., Wolf, B. <strong>Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.</strong> Molec. Genet. Metab. 64: 152-154, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9705240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9705240</a>] [<a href="https://doi.org/10.1006/mgme.1998.2706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9705240">Pomponio et al. (1998)</a> identified a 1466A-C transversion in exon 4 of the BTD gene, resulting in an asn489-to-thr (N489T) substitution in the putative glycosylation site of the BTD protein. The child was treated with oral biotin supplementation from age 2 months to 5 years. Biotin supplementation was then discontinued and the child, who was 8 years old at the time of report, had remained asymptomatic. Hearing and vision testing had been normal. He showed 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9705240" 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>.0009 BIOTINIDASE DEFICIENCY</strong>
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BTD, PHE403VAL AND ASP444HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893686 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893686;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893686?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001977 OR RCV000001981 OR RCV000021936 OR RCV000078064 OR RCV000501861 OR RCV000727665 OR RCV002381235 OR RCV004751192" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001977, RCV000001981, RCV000021936, RCV000078064, RCV000501861, RCV000727665, RCV002381235, RCV004751192" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001977...</a>
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<p>For discussion of the F403V/D444H double mutation in the BTD gene that was identified in patients with BTD deficiency (<a href="/entry/253260">253260</a>) by <a href="#8" class="mim-tip-reference" title="Norrgard, K. J., Pomponio, R. J., Hymes, J., Wolf, B. <strong>Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.</strong> Pediat. Res. 46: 20-27, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400129</a>] [<a href="https://doi.org/10.1203/00006450-199907000-00004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400129">Norrgard et al. (1999)</a>, see <a href="#0005">609019.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400129" 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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<a id="0010" class="mim-anchor"></a>
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<strong>.0010 BIOTINIDASE DEFICIENCY</strong>
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BTD, ARG79CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893687 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893687;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893687?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001982 OR RCV001815158" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001982, RCV001815158" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001982...</a>
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<p>In Turkish children with biotinidase deficiency (<a href="/entry/253260">253260</a>) identified both clinically and by newborn screening, <a href="#10" class="mim-tip-reference" title="Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B. <strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong> J. Inherit. Metab. Dis. 23: 120-128, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801053</a>] [<a href="https://doi.org/10.1023/a:1005609614443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10801053">Pomponio et al. (2000)</a> identified a 235C-T transition in the BTD gene, resulting in an arg79-to-cys (R79C) substitution. Some patients were homozygous and some compound heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801053" 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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<a id="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 BIOTINIDASE DEFICIENCY</strong>
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BTD, THR532MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893688 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893688;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893688?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001974 OR RCV000185809 OR RCV004601086 OR RCV004751190" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001974, RCV000185809, RCV004601086, RCV004751190" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001974...</a>
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<p>In Turkish children with biotinidase deficiency (<a href="/entry/253260">253260</a>), <a href="#10" class="mim-tip-reference" title="Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B. <strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong> J. Inherit. Metab. Dis. 23: 120-128, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801053</a>] [<a href="https://doi.org/10.1023/a:1005609614443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10801053">Pomponio et al. (2000)</a> identified homozygous 1595C-T transition in the BTD gene, resulting in a thr532-to-met (T532M) substitution in homozygous or compound heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801053" 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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<a id="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 BIOTINIDASE DEFICIENCY</strong>
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BTD, PHE361VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1204990361 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1204990361;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1204990361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1204990361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001251432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001251432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001251432</a>
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<p>Of 14 Brazilian children with biotinidase deficiency (<a href="/entry/253260">253260</a>) identified by newborn screening, <a href="#2" class="mim-tip-reference" title="Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B. <strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong> Am. J. Med. Genet. 179A: 978-982, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30912303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30912303</a>] [<a href="https://doi.org/10.1002/ajmg.a.61137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30912303">Carvalho et al. (2019)</a> identified 2 with a homozygous c.1081T-G transversion in exon 4 of the BTD gene, resulting in a phe361-to-val (F361V) substitution. Biotinidase enzyme activity in serum from both patients was in the partially deficient range. Serum enzyme testing in a mother from one of these patients showed biotinidase activity in the heterozygote range. Two other children were compound heterozygous for the F361V mutation and another BTD mutation, in one case with D444H (<a href="#0005">609019.0005</a>). Biotinidase enzyme activity in serum from both children was in the partially deficient range. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30912303" 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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<a id="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 BIOTINIDASE DEFICIENCY</strong>
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BTD, ALA534VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1210441433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1210441433;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1210441433?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1210441433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1210441433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001251433" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001251433" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001251433</a>
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<p>Of 14 Brazilian children with biotinidase deficiency (<a href="/entry/253260">253260</a>) identified by newborn screening, <a href="#2" class="mim-tip-reference" title="Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B. <strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong> Am. J. Med. Genet. 179A: 978-982, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30912303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30912303</a>] [<a href="https://doi.org/10.1002/ajmg.a.61137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30912303">Carvalho et al. (2019)</a> identified one with a homozygous c.1601C-T transition in exon 4 of the BTD gene, resulting in an ala534-to-val (A534V) substitution. Biotinidase deficiency in this child was in the profoundly deficient range. Two other children were compound heterozygous for A534V and D444H (<a href="#0005">609019.0005</a>). Biotinidase enzyme activity in serum from these children was in the partially deficient range. Based on these findings, <a href="#2" class="mim-tip-reference" title="Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B. <strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong> Am. J. Med. Genet. 179A: 978-982, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30912303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30912303</a>] [<a href="https://doi.org/10.1002/ajmg.a.61137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30912303">Carvalho et al. (2019)</a> concluded that the A534V mutation results in severe enzyme deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30912303" 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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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
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|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bell2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
|
|
<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
|
|
Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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=21228398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/scitranslmed.3001756" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
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|
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|
|
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|
|
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|
|
<a id="Carvalho2019" class="mim-anchor"></a>
|
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|
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Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B.
|
|
<strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong>
|
|
Am. J. Med. Genet. 179A: 978-982, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30912303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30912303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30912303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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[<a href="https://doi.org/10.1002/ajmg.a.61137" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cole1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B.
|
|
<strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong>
|
|
J. Biol. Chem. 269: 6566-6570, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7509806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7509806</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7509806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
|
|
|
|
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cole1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cole, H., Weremowicz, S., Morton, C. C., Wolf, B.
|
|
<strong>Localization of serum biotinidase (BTD) to human chromosome 3 in band p25.</strong>
|
|
Genomics 22: 662-663, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1449" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gordon1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gordon, A.
|
|
<strong>Biotinidase mutational 'hotspot'. (Letter)</strong>
|
|
Nature Genet. 13: 144-145, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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[<a href="https://doi.org/10.1038/ng0696-144b" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Hernandez-Vazquez2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hernandez-Vazquez, A., Wolf, B., Pindolia, K., Ortega-Cuellar, D., Hernandez-Gonzalez, R., Heredia-Antunez, A., Ibarra-Gonzalez, I., Velazquez-Arellano, A.
|
|
<strong>Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.</strong>
|
|
Molec. Genet. Metab. 110: 248-254, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24075304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24075304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24075304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1016/j.ymgme.2013.08.018" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Knight1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Knight, H. C., Reynolds, T. R., Meyers, G. A., Pomponio, R. J., Buck, G. A., Wolf, B.
|
|
<strong>Structure of the human biotinidase gene.</strong>
|
|
Mammalian Genome 9: 327-330, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9530634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9530634</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9530634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900760" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Norrgard1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Norrgard, K. J., Pomponio, R. J., Hymes, J., Wolf, B.
|
|
<strong>Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.</strong>
|
|
Pediat. Res. 46: 20-27, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400129</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400129" 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/10.1203/00006450-199907000-00004" target="_blank">Full Text</a>]
|
|
|
|
|
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Norrgard1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Norrgard, K. J., Swango, K. L., Wolf, B.
|
|
<strong>Mutation (D444H) in the biotinidase gene causes approximately 50% loss of enzyme activity and is common in the general population. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 59 (suppl.): A275 only, 1996.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Pomponio2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B.
|
|
<strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong>
|
|
J. Inherit. Metab. Dis. 23: 120-128, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801053" 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/10.1023/a:1005609614443" target="_blank">Full Text</a>]
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|
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|
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|
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Pomponio, R. J., Hymes, J., Reynolds, T. R., Meyers, G. A., Fleischhauer, K., Buck, G. A., Wolf, B.
|
|
<strong>Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis.</strong>
|
|
Pediat. Res. 42: 840-848, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9396567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9396567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9396567" 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/10.1203/00006450-199712000-00020" target="_blank">Full Text</a>]
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|
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Pomponio, R. J., Narasimhan, V., Reynolds, T. R., Buck, G. A., Povirk, L. F., Wolf, B.
|
|
<strong>Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure.</strong>
|
|
Hum. Molec. Genet. 5: 1657-1661, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8894703" 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/5.10.1657" target="_blank">Full Text</a>]
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Pomponio, R. J., Norrgard, K. J., Hymes, J., Reynolds, T. R., Buck, G. A., Baumgartner, R., Suormala, T., Wolf, B.
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<strong>Arg538 to cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children.</strong>
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Hum. Genet. 99: 506-512, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9099842" 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/10.1007/s004390050397" target="_blank">Full Text</a>]
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Pomponio, R. J., Reynolds, T. R., Cole, H., Buck, G. A., Wolf, B.
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<strong>Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency.</strong>
|
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Nature Genet. 11: 96-98, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550325" 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/ng0995-96" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Pomponio1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pomponio, R. J., Reynolds, T. R., Mandel, H., Admoni, O., Melone, P. D., Buck, G. A., Wolf, B.
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<strong>Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3-prime splice acceptor site within an exon of the human biotinidase gene.</strong>
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Hum. Molec. Genet. 6: 739-745, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158148</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158148" 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/6.5.739" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Pomponio1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pomponio, R. J., Yamaguchi, A., Arashima, S., Hymes, J., Wolf, B.
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<strong>Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.</strong>
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Molec. Genet. Metab. 64: 152-154, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9705240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9705240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9705240" 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/10.1006/mgme.1998.2706" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Swango1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Swango, K. L., Demirkol, M., Huner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., Wolf, B.
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<strong>Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.</strong>
|
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Hum. Genet. 102: 571-575, 1998. Note: Erratum: Hum. Genet. 102: 712 only, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9654207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9654207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9654207" 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/10.1007/s004390050742" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Wolf1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J.
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<strong>Profound biotinidase deficiency in two asymptomatic adults.</strong>
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Am. J. Med. Genet. 73: 5-9, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9375914" 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/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u" target="_blank">Full Text</a>]
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</ol>
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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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Hilary J. Vernon - updated : 08/06/2020
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/12/2014<br>Cassandra L. Kniffin - updated : 11/11/2004
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</div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 11/8/2004
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</span>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/13/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/06/2020<br>carol : 07/16/2020<br>carol : 08/13/2015<br>mcolton : 8/12/2015<br>alopez : 2/21/2014<br>mcolton : 2/18/2014<br>ckniffin : 2/12/2014<br>alopez : 11/27/2012<br>carol : 12/21/2011<br>alopez : 7/28/2011<br>alopez : 4/6/2011<br>carol : 9/10/2009<br>terry : 8/3/2005<br>carol : 11/29/2004<br>ckniffin : 11/11/2004
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</span>
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 609019
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</span>
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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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BIOTINIDASE; BTD
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: BTD</em></strong>
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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="mim-text-font">
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<strong>SNOMEDCT:</strong> 8808004;
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<strong>ICD10CM:</strong> D81.810;
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</span>
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</p>
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<br />
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 3p25.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:15,601,361-15,722,516 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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3p25.1
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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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Biotinidase deficiency
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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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253260
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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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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Serum biotinidase (BTD; EC 3.5.1.12) catalyzes the hydrolysis of biocytin, a normal product of biotin-dependent carboxylase degradation, to biotin and lysine. The process results in the regeneration of free biotin. Biotin is an essential water-soluble vitamin and is the coenzyme for 4 carboxylases necessary for normal metabolism in humans: pyruvate carboxylase (PCC; 608786), propionyl-CoA carboxylase (PCCA; 232000), alpha-methylcrotonyl-CoA carboxylase (see MCCC1; 609010), and acetyl-CoA carboxylase (ACACA; 200350) (summary by Cole et al., 1994). </p><p>Pomponio et al. (1997) stated that biotinidase has also been shown to have biotinyl-transferase activity. </p>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</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>Cole et al. (1994) cloned and sequenced a cDNA corresponding to the BTD gene from a human hepatic cDNA library. The deduced 543-amino acid protein has a molecular mass of approximately 57 kD and contains 6 potential N-linked glycosylation sites. Northern blot analysis detected BTD mRNA in human heart, brain, placenta, liver, lung, skeletal muscle, kidney, and pancreas. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</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>Knight et al. (1998) determined that the BTD gene contains 4 exons and spans at least 23 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</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>Using fluorescence in situ hybridization, Cole et al. (1994) mapped the BTD gene to chromosome 3p25. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</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 10 of 25 patients with biotinidase deficiency (253260), Pomponio et al. (1995) identified an allele with a 7-bp deletion and a 3-bp insertion in the BTD gene (609019.0001). </p><p>In 37 symptomatic children (30 index cases and 7 sibs) with profound biotinidase deficiency, Pomponio et al. (1997) identified 21 mutations in the BTD gene. The 2 most common mutations were the del7/ins3 mutation and R538C (609019.0003); these 2 mutations were found in 31 of 60 alleles (52%), whereas the remainder of the alleles were accounted for by the 19 other unique mutations. </p><p>In 2 unrelated asymptomatic adults with biotinidase deficiency who were diagnosed because their children were identified by newborn screening, Wolf et al. (1997) found homozygous mutations in the BTD gene (609019.0005 and 609019.0006). Wolf et al. (1997) concluded that epigenetic factors may protect some enzyme-deficient individuals from developing symptoms. </p><p>Pomponio et al. (2000) identified mutations in the BTD gene (see, e.g., 609019.0007; 609019.0010; 609019.0011) in Turkish children with biotinidase deficiency identified both clinically and by newborn screening. </p><p>Carvalho et al. (2019) reported molecular and serum enzyme testing results in 14 Brazilian children with biotinidase deficiency who were identified by newborn screening. Nine novel mutations were identified, including 2 deletions and 7 missense mutations. Seven of the mutations were found in exon 4, which encodes the C terminus. Among the missense mutations that were identified in homozygous state, F361V (609019.0012) led to partial biotinidase deficiency in 2 unrelated patients, and A534V (609019.0013) led to profound biotinidase deficiency in 1 patient. The previously reported D444H mutation (609019.0005) was found in compound heterozygosity in 7 patients; 5 of the patients had partial biotinidase deficiency, including one with compound heterozygosity for A534V and one with compound heterozygosity for F361V, and 2 of the patients had possible partial biotinidase deficiency. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</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>Hernandez-Vazquez et al. (2013) studied the metabolic features of 3-week-old Btd-null mice that had been fed a biotin-deficient diet for 5 days. The mice showed no phenotypic alterations characteristic of biotinidase deficiency, such as seizures, hypotonia, ataxia, or hair or skin abnormalities. Liver samples from the mice showed decreased cellular energy, with an increase in the AMP/ATP ratio and an increase in phosphorylation of AMP-activated protein kinase (AMPK; see 602739). There was inhibition of the signaling protein mTOR (601231), which is a driver of protein synthesis and growth. The transcripts of several central carbon metabolism genes were also changed: GCK (138079) and FASN (600212) were increased, whereas those of PCK1 (614168) and CPT1 (600528) were decreased. The mice also showed increased serum levels of free fatty acids, decreased levels of blood glucose, and increased insulin sensitivity. These findings indicated a severe energy deficit and altered energy metabolism in the absence of adequate biotin. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>13 Selected Examples):</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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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 BIOTINIDASE DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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BTD, 7-BP DEL/3-BP INS
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<br />
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SNP: rs80338684,
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ClinVar: RCV000001972, RCV000078084
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 10 of 25 patients with biotinidase deficiency (253260), Pomponio et al. (1995) identified an allele with a 7-bp deletion and a 3-bp insertion (98-104del7ins3), immediately 3-prime to a 12-bp polypyrimidine sequence in the BTD gene. The deletion/insertion resulted in a frameshift that was predicted to terminate with a stop codon at amino acid 68, resulting in a truncated protein with an amino acid sequence different from that of biotinidase; the other allele contained the normal sequence. Three other patients were homozygous for the mutation. These 3 patients lacked crossreacting material to antibodies prepared against normal human serum biotinidase. The parents of 1 of the 3 patients were first cousins and those of a second were third cousins, whereas the parents of the third patient were not consanguineous. Racial and ethnic diversity and worldwide distribution of the patients studied suggested that the relatively high frequency of the mutation did not arise through a founder effect, and the authors suggested that it was a mutation hotspot. </p><p>Gordon (1996), who referred to the mutation as arising through an indel (insertion/deletion) event, questioned the 'hotspot' hypothesis and suggested that, like the delF508 mutation (219700.0001) for cystic fibrosis, this may be a very ancient mutation. </p>
|
|
</span>
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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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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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BTD, 15-BP DEL/11-BP INS
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<br />
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SNP: rs672601248,
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ClinVar: RCV000169138, RCV000728443
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
<p>In a child with profound biotinidase deficiency (253260), Pomponio et al. (1996) identified homozygosity for a 15-bp deletion/11-bp insertion mutation within exon D (nucleotides 1059-1359 of the sequence reported by Cole et al. (1994)) of the BTD gene. The mutation resulted in a frameshift predicted to terminate the polypeptide prematurely. The authors proposed 2 possible mechanisms to account for this mutation, both of which involved formation of a quasipalindromic structure in the replicating DNA strands. </p>
|
|
</span>
|
|
</div>
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|
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<div>
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|
<br />
|
|
</div>
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</div>
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|
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
BTD, ARG538CYS
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<br />
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SNP: rs80338686,
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|
gnomAD: rs80338686,
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ClinVar: RCV000001975, RCV000790794, RCV003242960, RCV003421895
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 10 of 30 symptomatic children with profound biotinidase deficiency (253260), Pomponio et al. (1997) identified a 1612C-T transition in a CpG dinucleotide in exon D of the BTD gene, resulting in an arg538-to-cys (R538C) substitution. Five of the patients were compound heterozygous for this mutation and a deletion/insertion mutation (609019.0001). There was no detectable biotinidase protein in sera of homozygous children, and the authors suggested that the R538C mutation results in abnormal disulfide bond formation, rapid degradation of the aberrant enzyme, and failure to secrete the mutant enzyme from the cells into the blood. Pomponio et al. (1997) reported that the R538C mutation is the second most common mutation causing biotinidase deficiency. </p>
|
|
</span>
|
|
</div>
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|
|
<div>
|
|
<br />
|
|
</div>
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|
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|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
BTD, GLY34SER
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<br />
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|
|
SNP: rs119103232,
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|
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gnomAD: rs119103232,
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ClinVar: RCV000001976, RCV004751191
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|
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|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated individuals with profound biotinidase deficiency (253260), Pomponio et al. (1997) identified a 100G-A transition in the BTD gene, located 57 bases downstream of the authentic splice acceptor site in exon B, resulting in a gly34-to-ser (G34S) substitution. The transition also generated a 3-prime splice acceptor site. The sequence of the PCR-amplified cDNA from the homozygous child revealed that all the product was shorter than that of normal individuals and was the result of aberrant splicing. The aberrantly spliced transcript lacks 57 nucleotides, including a second in-frame ATG, that encode most of the putative signal peptide and results in an in-frame deletion of 19 amino acids. The mutation resulted in failure to secrete the aberrant protein into the blood. This was the first reported example in which a point mutation creates a cryptic 3-prime splice acceptor site motif that is used preferentially over the upstream authentic splice site. Pomponio et al. (1997) stated that preferential usage of the downstream splice site was not consistent with the 5-prime-to-3-prime scanning model of RNA splicing, but was consistent with the exon definition model. </p>
|
|
</span>
|
|
</div>
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, ALA171THR AND ASP444HIS
|
|
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|
|
<br />
|
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|
|
SNP: rs13073139, rs13078881,
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|
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|
|
|
gnomAD: rs13073139, rs13078881,
|
|
|
|
|
|
ClinVar: RCV000001977, RCV000001981, RCV000021936, RCV000031859, RCV000078064, RCV000078073, RCV002381235, RCV002514126, RCV004751192
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an asymptomatic man with biotinidase deficiency (253260) who was diagnosed because his affected child was identified by newborn screening, Wolf et al. (1997) identified a homozygous allelic double missense mutation in the BTD gene: a 511G-A transition, resulting in an ala171-to-thr (A171T) substitution, which had been described by Cole et al. (1994), and a 1330G-C transversion, resulting in an asp444-to-his (D444H) substitution, which had been described by Norrgard et al. (1996). The daughter had the same genotype; the parents of the father and his wife were heterozygous for this doubly mutant allele. </p><p>Swango et al. (1998) found that 18 of 19 randomly selected individuals with partial biotinidase deficiency (10 to 30% activity) were heterozygous for the D444H mutation. Previous studies had indicated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. Swango et al. (1998) compared the D444H mutation to the Duarte variant of galactosemia (230400.0005). The D444H mutation in 1 allele in combination with a mutation for profound deficiency in the other allele is a common cause of partial biotinidase deficiency. </p><p>Norrgard et al. (1999) found the double mutation (A171T/D444H) to be the second most common allele identified by newborn screening, appearing in 17.3% of alleles. They observed a second double mutation (F403V/D444H); see 609019.0009. It was unknown whether A171T or F403V must act in concert with D444H to produce profound biotinyl-hydrolase and -transferase deficiencies. Either the A171T or the F403V mutation alone could produce a nonfunctional enzyme, although neither had been observed alone. Although A171T/D444H was very frequent in newborn screening alleles, it was found in none of the patients whose disorder had been detected on the basis of symptoms. </p><p>In a preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, Bell et al. (2011) found that the D444H mutation in BTD is a polymorphism carried by asymptomatic individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, ASP252GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28934601,
|
|
|
|
|
|
gnomAD: rs28934601,
|
|
|
|
|
|
ClinVar: RCV000001978, RCV000445043
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an asymptomatic woman with biotinidase deficiency (253260) who was diagnosed after her child was identified by newborn screening, Wolf et al. (1997) identified a homozygous 755A-G transition, resulting in an asp252-to-gly (D252G) substitution. Her parents were heterozygous for the mutation. Her husband was heterozygous for a missense mutation (Q456H; 609019.0007). The enzyme-deficient daughter was a compound heterozygote for the mutations found in the mother and father. The son, who was identified through newborn screening, was presumably also a compound heterozygote for these 2 mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, GLN456HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338685,
|
|
|
|
|
|
gnomAD: rs80338685,
|
|
|
|
|
|
ClinVar: RCV000001979, RCV000078065, RCV001251700, RCV004018539, RCV004751193
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Wolf et al. (1997) identified a heterozygous 1368A-C transversion in the BTD gene, resulting in a gln456-to-his (Q456H) substitution (originally published as GLN556HIS) in a man whose child was diagnosed with biotinidase deficiency (253260). The affected child was compound heterozygous for the Q456H mutation and D252G (609019.0006). </p><p>Pomponio et al. (2000) identified homozygosity for the Q456H mutation in a clinically ascertained child in the Turkish population. They also identified the Q456H mutation in homozygosity or compound heterozygosity in 2 Turkish children ascertained by newborn screening. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, ASN489THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893692,
|
|
|
|
|
|
gnomAD: rs104893692,
|
|
|
|
|
|
ClinVar: RCV000001980, RCV002272006, RCV003230341
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese child with biotinidase deficiency (253260) identified in a pilot newborn screening program in Sapporo, Japan, Pomponio et al. (1998) identified a 1466A-C transversion in exon 4 of the BTD gene, resulting in an asn489-to-thr (N489T) substitution in the putative glycosylation site of the BTD protein. The child was treated with oral biotin supplementation from age 2 months to 5 years. Biotin supplementation was then discontinued and the child, who was 8 years old at the time of report, had remained asymptomatic. Hearing and vision testing had been normal. He showed 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, PHE403VAL AND ASP444HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893686,
|
|
|
|
|
|
gnomAD: rs104893686,
|
|
|
|
|
|
ClinVar: RCV000001977, RCV000001981, RCV000021936, RCV000078064, RCV000501861, RCV000727665, RCV002381235, RCV004751192
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the F403V/D444H double mutation in the BTD gene that was identified in patients with BTD deficiency (253260) by Norrgard et al. (1999), see 609019.0005. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, ARG79CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893687,
|
|
|
|
|
|
gnomAD: rs104893687,
|
|
|
|
|
|
ClinVar: RCV000001982, RCV001815158
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Turkish children with biotinidase deficiency (253260) identified both clinically and by newborn screening, Pomponio et al. (2000) identified a 235C-T transition in the BTD gene, resulting in an arg79-to-cys (R79C) substitution. Some patients were homozygous and some compound heterozygous. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, THR532MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893688,
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|
|
|
|
|
gnomAD: rs104893688,
|
|
|
|
|
|
ClinVar: RCV000001974, RCV000185809, RCV004601086, RCV004751190
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Turkish children with biotinidase deficiency (253260), Pomponio et al. (2000) identified homozygous 1595C-T transition in the BTD gene, resulting in a thr532-to-met (T532M) substitution in homozygous or compound heterozygous state. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 BIOTINIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BTD, PHE361VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1204990361,
|
|
|
|
|
|
|
|
ClinVar: RCV001251432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Of 14 Brazilian children with biotinidase deficiency (253260) identified by newborn screening, Carvalho et al. (2019) identified 2 with a homozygous c.1081T-G transversion in exon 4 of the BTD gene, resulting in a phe361-to-val (F361V) substitution. Biotinidase enzyme activity in serum from both patients was in the partially deficient range. Serum enzyme testing in a mother from one of these patients showed biotinidase activity in the heterozygote range. Two other children were compound heterozygous for the F361V mutation and another BTD mutation, in one case with D444H (609019.0005). Biotinidase enzyme activity in serum from both children was in the partially deficient range. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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<h4>
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<span class="mim-font">
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<strong>.0013 BIOTINIDASE DEFICIENCY</strong>
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</h4>
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<span class="mim-text-font">
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BTD, ALA534VAL
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<br />
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SNP: rs1210441433,
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gnomAD: rs1210441433,
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ClinVar: RCV001251433
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<p>Of 14 Brazilian children with biotinidase deficiency (253260) identified by newborn screening, Carvalho et al. (2019) identified one with a homozygous c.1601C-T transition in exon 4 of the BTD gene, resulting in an ala534-to-val (A534V) substitution. Biotinidase deficiency in this child was in the profoundly deficient range. Two other children were compound heterozygous for A534V and D444H (609019.0005). Biotinidase enzyme activity in serum from these children was in the partially deficient range. Based on these findings, Carvalho et al. (2019) concluded that the A534V mutation results in severe enzyme deficiency. </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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<ol>
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<p class="mim-text-font">
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Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
|
|
<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
|
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Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
|
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|
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[PubMed: 21228398]
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[Full Text: https://doi.org/10.1126/scitranslmed.3001756]
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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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Carvalho, N. O., del Castillo, D. M., Januario, J. N., Starling, A. L. P., Arantes, R. R., Norton, R. C., Viana, M. B.
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<strong>Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.</strong>
|
|
Am. J. Med. Genet. 179A: 978-982, 2019.
|
|
|
|
|
|
[PubMed: 30912303]
|
|
|
|
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|
[Full Text: https://doi.org/10.1002/ajmg.a.61137]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Cole, H., Reynolds, T. R., Lockyer, J. M., Buck, G. A., Denson, T., Spence, J. E., Hymes, J., Wolf, B.
|
|
<strong>Human serum biotinidase: cDNA cloning, sequence, and characterization.</strong>
|
|
J. Biol. Chem. 269: 6566-6570, 1994.
|
|
|
|
|
|
[PubMed: 7509806]
|
|
|
|
|
|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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Cole, H., Weremowicz, S., Morton, C. C., Wolf, B.
|
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<strong>Localization of serum biotinidase (BTD) to human chromosome 3 in band p25.</strong>
|
|
Genomics 22: 662-663, 1994.
|
|
|
|
|
|
[PubMed: 8001986]
|
|
|
|
|
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[Full Text: https://doi.org/10.1006/geno.1994.1449]
|
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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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Gordon, A.
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<strong>Biotinidase mutational 'hotspot'. (Letter)</strong>
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Nature Genet. 13: 144-145, 1996.
|
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|
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[PubMed: 8640218]
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|
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[Full Text: https://doi.org/10.1038/ng0696-144b]
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</p>
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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Hernandez-Vazquez, A., Wolf, B., Pindolia, K., Ortega-Cuellar, D., Hernandez-Gonzalez, R., Heredia-Antunez, A., Ibarra-Gonzalez, I., Velazquez-Arellano, A.
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<strong>Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.</strong>
|
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Molec. Genet. Metab. 110: 248-254, 2013.
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[PubMed: 24075304]
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[Full Text: https://doi.org/10.1016/j.ymgme.2013.08.018]
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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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Knight, H. C., Reynolds, T. R., Meyers, G. A., Pomponio, R. J., Buck, G. A., Wolf, B.
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<strong>Structure of the human biotinidase gene.</strong>
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Mammalian Genome 9: 327-330, 1998.
|
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|
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[PubMed: 9530634]
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[Full Text: https://doi.org/10.1007/s003359900760]
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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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Norrgard, K. J., Pomponio, R. J., Hymes, J., Wolf, B.
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<strong>Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.</strong>
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Pediat. Res. 46: 20-27, 1999.
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[PubMed: 10400129]
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[Full Text: https://doi.org/10.1203/00006450-199907000-00004]
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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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Norrgard, K. J., Swango, K. L., Wolf, B.
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<strong>Mutation (D444H) in the biotinidase gene causes approximately 50% loss of enzyme activity and is common in the general population. (Abstract)</strong>
|
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Am. J. Hum. Genet. 59 (suppl.): A275 only, 1996.
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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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Pomponio, R. J., Coskun, T., Demirkol, M., Tokatli, A., Ozalp, I., Huner, G., Baykal, T., Wolf, B.
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<strong>Novel mutations cause biotinidase deficiency in Turkish children.</strong>
|
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J. Inherit. Metab. Dis. 23: 120-128, 2000.
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[PubMed: 10801053]
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[Full Text: https://doi.org/10.1023/a:1005609614443]
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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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Pomponio, R. J., Hymes, J., Reynolds, T. R., Meyers, G. A., Fleischhauer, K., Buck, G. A., Wolf, B.
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<strong>Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis.</strong>
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Pediat. Res. 42: 840-848, 1997.
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[PubMed: 9396567]
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[Full Text: https://doi.org/10.1203/00006450-199712000-00020]
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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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Pomponio, R. J., Narasimhan, V., Reynolds, T. R., Buck, G. A., Povirk, L. F., Wolf, B.
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<strong>Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure.</strong>
|
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Hum. Molec. Genet. 5: 1657-1661, 1996.
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[PubMed: 8894703]
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|
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[Full Text: https://doi.org/10.1093/hmg/5.10.1657]
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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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Pomponio, R. J., Norrgard, K. J., Hymes, J., Reynolds, T. R., Buck, G. A., Baumgartner, R., Suormala, T., Wolf, B.
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<strong>Arg538 to cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children.</strong>
|
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Hum. Genet. 99: 506-512, 1997.
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[PubMed: 9099842]
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[Full Text: https://doi.org/10.1007/s004390050397]
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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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Pomponio, R. J., Reynolds, T. R., Cole, H., Buck, G. A., Wolf, B.
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<strong>Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency.</strong>
|
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Nature Genet. 11: 96-98, 1995.
|
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|
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[PubMed: 7550325]
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[Full Text: https://doi.org/10.1038/ng0995-96]
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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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Pomponio, R. J., Reynolds, T. R., Mandel, H., Admoni, O., Melone, P. D., Buck, G. A., Wolf, B.
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<strong>Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3-prime splice acceptor site within an exon of the human biotinidase gene.</strong>
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Hum. Molec. Genet. 6: 739-745, 1997.
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[PubMed: 9158148]
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[Full Text: https://doi.org/10.1093/hmg/6.5.739]
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</p>
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<li>
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<p class="mim-text-font">
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Pomponio, R. J., Yamaguchi, A., Arashima, S., Hymes, J., Wolf, B.
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<strong>Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.</strong>
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Molec. Genet. Metab. 64: 152-154, 1998.
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[PubMed: 9705240]
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[Full Text: https://doi.org/10.1006/mgme.1998.2706]
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<li>
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<p class="mim-text-font">
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Swango, K. L., Demirkol, M., Huner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., Wolf, B.
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<strong>Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.</strong>
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Hum. Genet. 102: 571-575, 1998. Note: Erratum: Hum. Genet. 102: 712 only, 1998.
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[PubMed: 9654207]
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[Full Text: https://doi.org/10.1007/s004390050742]
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</p>
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<li>
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<p class="mim-text-font">
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Wolf, B., Norrgard, K., Pomponio, R. J., Mock, D. M., McVoy, J. R. S., Fleischhauer, K., Shapiro, S., Blitzer, M. G., Hymes, J.
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<strong>Profound biotinidase deficiency in two asymptomatic adults.</strong>
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Am. J. Med. Genet. 73: 5-9, 1997.
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[PubMed: 9375914]
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[Full Text: https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<5::aid-ajmg2>3.0.co;2-u]
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Hilary J. Vernon - updated : 08/06/2020<br>Cassandra L. Kniffin - updated : 2/12/2014<br>Cassandra L. Kniffin - updated : 11/11/2004
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carol : 05/13/2022<br>carol : 08/06/2020<br>carol : 07/16/2020<br>carol : 08/13/2015<br>mcolton : 8/12/2015<br>alopez : 2/21/2014<br>mcolton : 2/18/2014<br>ckniffin : 2/12/2014<br>alopez : 11/27/2012<br>carol : 12/21/2011<br>alopez : 7/28/2011<br>alopez : 4/6/2011<br>carol : 9/10/2009<br>terry : 8/3/2005<br>carol : 11/29/2004<br>ckniffin : 11/11/2004
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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