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Entry
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- *613381 - CYSTATHIONINE BETA-SYNTHASE; CBS
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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">*613381</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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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#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/613381">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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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=ENSG00000160200;t=ENST00000398165" 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=875" 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=613381" 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="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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</span>
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</span>
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</div>
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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=ENSG00000160200;t=ENST00000398165" 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_000071,NM_001178008,NM_001178009,NM_001320298,NM_001321072,XM_011529774,XM_011529777,XM_011529783,XM_017028491,XM_047441017,XM_047441018,XM_047441019,XM_047441020,XM_047441021,XM_047441022,XM_047441023,XM_047441024,XM_047441025,XM_047441026,XM_047441027,XM_047441028,XM_047441029,XM_047441030,XM_047441031,XM_047441032,XM_047441033,XR_001754915,XR_007067793" 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_000071" 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=613381" 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://www.proteinatlas.org/search/CBS" 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/388716,543959,558582,1289362,3776242,3776243,3850687,4557415,6807800,12653343,15030237,15147371,16307396,30583147,45535523,60650132,75766725,119629912,119629913,119629914,119629915,119629916,119629917,119629918,119629919,119629920,189053933,221040118,221043448,259430849,259454206,259464663,259659655,259691443,259694025,295821200,295821202,300546223,300555311,300562769,300579341,300644289,300653600,768021845,768021856,768021879,998429209,1007358255,1034627674,2217338300,2217338303,2217338305,2217338307,2217338309,2217338311,2217338313,2217338315,2217338317,2217338319,2217338321,2217338323,2217338326,2217338328,2217338330,2217338332,2217338336,2462583386,2462583388,2462583390,2462583392,2462583394,2462583396,2462583398,2462583400,2462583402,2462583404,2462583406,2462583408,2462583410,2462583412,2462583414,2462583416,2462583418,2462583420,2462583423,2462583425,2462583427" 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/P35520" 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=875" 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=ENSG00000160200;t=ENST00000398165" 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=CBS" 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=CBS" 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+875" 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/CBS" 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:875" 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/875" 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=chr21&hgg_gene=ENST00000398165.8&hgg_start=43053191&hgg_end=43076873&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:1550" 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:1550" 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/cbs" 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=613381[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=613381[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://www.deciphergenomics.org/gene/CBS/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000160200" 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=CBS" 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=CBS" 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=CBS" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CBS&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/PA26123" 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:1550" 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/FBgn0031148.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:88285" 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/CBS#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:88285" 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/875/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=875" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00013866;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00013866 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00018783;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00018783 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-021030-3" 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:875" 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=CBS&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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</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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613381
|
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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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CYSTATHIONINE BETA-SYNTHASE; CBS
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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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CBS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CBS</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/21/142?start=-3&limit=10&highlight=142">21q22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr21:43053191-43076873&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'})">21:43,053,191-43,076,873</a> </span>
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</em>
|
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</strong>
|
|
<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>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
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>
|
|
<th>
|
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Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/21/142?start=-3&limit=10&highlight=142">
|
|
21q22.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Homocystinuria, B6-responsive and nonresponsive types
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/236200"> 236200 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<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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|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Thrombosis, hyperhomocysteinemic
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</span>
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PheneGene Graphics <span class="caret"></span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>The CBS gene encodes cystathionine beta-synthase (<a href="https://enzyme.expasy.org/EC/4.2.1.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 4.2.1.22</a>), which catalyzes the first irreversible step of transsulfuration. The enzyme conjugates homocysteine and serine to form cystathionine, which is subsequently converted into cysteine and alpha-ketobutyrate. Homocysteine can also undergo remethylation to form methionine. The CBS enzyme is a homotetramer of 63-kD subunits and requires pyridoxal phosphate and heme for activity. It can also be stimulated by the addition of S-adenosylmethionine (AdoMet) (<a href="#28" class="mim-tip-reference" title="Kraus, J. P., Le, K., Swaroop, M., Ohura, T., Tahara, T., Rosenberg, L. E., Roper, M. D., Kozich, V. <strong>Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells.</strong> Hum. Molec. Genet. 2: 1633-1638, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7903580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7903580</a>] [<a href="https://doi.org/10.1093/hmg/2.10.1633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7903580">Kraus et al., 1993</a>; <a href="#47" class="mim-tip-reference" title="Shan, X., Dunbrack, R. L., Jr., Christopher, S. A., Kruger, W. D. <strong>Mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient-derived mutations in cis.</strong> Hum. Molec. Genet. 10: 635-643, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230183</a>] [<a href="https://doi.org/10.1093/hmg/10.6.635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11230183">Shan et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7903580+11230183" 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="#28" class="mim-tip-reference" title="Kraus, J. P., Le, K., Swaroop, M., Ohura, T., Tahara, T., Rosenberg, L. E., Roper, M. D., Kozich, V. <strong>Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells.</strong> Hum. Molec. Genet. 2: 1633-1638, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7903580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7903580</a>] [<a href="https://doi.org/10.1093/hmg/2.10.1633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7903580">Kraus et al. (1993)</a> cloned the human CBS gene from a human liver cDNA library. The deduced 551-residue protein showed about 90% identity with the rat protein. Northern blot analysis identified a major 2.7-kb mRNA transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7903580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Chasse, J. F., Paly, E., Paris, D., Paul, V., Sinet, P. M., Kamoun, P., London, J. <strong>Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs.</strong> Biochem. Biophys. Res. Commun. 211: 826-832, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7598711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7598711</a>] [<a href="https://doi.org/10.1006/bbrc.1995.1886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7598711">Chasse et al. (1995)</a> isolated clones corresponding to the CBS gene from a human liver cDNA library. The gene is expressed as a 2.5-kb mRNA species mostly in liver and pancreas, with faint expression in brain, heart, kidney and lung. In addition, a 3.7-kb transcript was found in pancreas and liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7598711" 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>Using in situ hybridization and Northern blot analysis, <a href="#43" class="mim-tip-reference" title="Robert, K., Vialard, F., Thiery, E., Toyama, K., Sinet, P.-M., Janel, N., London, J. <strong>Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain.</strong> J. Histochem. Cytochem. 51: 363-371, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588964</a>] [<a href="https://doi.org/10.1177/002215540305100311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588964">Robert et al. (2003)</a> found expression of the Cbs gene in early mouse development in the liver and in the skeletal, cardiac, and nervous systems. Expression declined in the nervous system in the late embryonic stages, whereas it increased in the brain after birth, peaking during cerebellar development. In the adult brain, expression was strongest in the Purkinje cell layer and in the hippocampus. Immunohistochemical analyses showed that the Cbs protein was localized in most areas of the brain, but predominantly in the cell bodies and neuronal processes of Purkinje cells and Ammon's horn neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588964" 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="#8" class="mim-tip-reference" title="Chasse, J. F., Paul, V., Escanez, R., Kamoun, P., London, J. <strong>Human cystathionine beta-synthase: gene organization and expression of different 5-prime alternative splicing.</strong> Mammalian Genome 8: 917-921, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9383285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9383285</a>] [<a href="https://doi.org/10.1007/s003359900611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9383285">Chasse et al. (1997)</a> reported that the human CBS gene spans over 30 kb and contains 19 exons. There are 3 different 5-prime untranslated regions, including 3 different exons 1: exon 1a, 1b, and 1c. Exons 1a and 1b are 390 bp apart and are linked to exon 2 in cDNAs reported by the authors. Exon 1c, which is linked to exon 5 in another cDNA, is 7 kb from exon 1b. All splice sites conform to the GT/AG rule, including those from exon 1a or 1b to exon 2 and from exon 1c to exon 5. Their results suggested that the mRNAs containing the different exons 1 are under the control of different promoters. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9383285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By genomic sequence analysis, <a href="#29" class="mim-tip-reference" title="Kraus, J. P., Oliveriusova, J., Sokolova, J., Kraus, E., Vlcek, C., de Franchis, R., Maclean, K. N., Bao, L., Bukovska, G., Patterson, D., Paces, V., Ansorge, W., Kozich, V. <strong>The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.</strong> Genomics 52: 312-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790750</a>] [<a href="https://doi.org/10.1006/geno.1998.5437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790750">Kraus et al. (1998)</a> determined that the CBS gene contains 23 exons, ranging in size from 42 to 299 bp. The 5-prime UTR is formed by 1 of 5 alternatively used exons and 1 invariably present exon. The 3-prime UTR is encoded by exons 16 and 17. <a href="#29" class="mim-tip-reference" title="Kraus, J. P., Oliveriusova, J., Sokolova, J., Kraus, E., Vlcek, C., de Franchis, R., Maclean, K. N., Bao, L., Bukovska, G., Patterson, D., Paces, V., Ansorge, W., Kozich, V. <strong>The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.</strong> Genomics 52: 312-324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790750</a>] [<a href="https://doi.org/10.1006/geno.1998.5437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790750">Kraus et al. (1998)</a> also described 2 alternatively used GC-rich promoter regions. The authors noted that the CBS locus contains an unusually high number of Alu repeats and suggested that these may predispose the gene to deleterious rearrangements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790750" 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>Studying somatic cell hybrids between human fibroblasts with normal cystathionine beta-synthase activity and hamster cells without this enzyme activity, Skovby et al. (<a href="#51" class="mim-tip-reference" title="Skovby, F., Krassikoff, N., Francke, U. <strong>Assignment of the gene for cystathionine beta-synthase (CBS) to human chromosome 21 in somatic cell hybrids. (Abstract)</strong> Cytogenet. Cell Genet. 37: 585 only, 1984."None>1984</a>, <a href="#52" class="mim-tip-reference" title="Skovby, F., Krassikoff, N., Francke, U. <strong>Assignment of the gene for cystathionine beta-synthase to human chromosome 21 in somatic cell hybrids.</strong> Hum. Genet. 65: 291-294, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6583157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6583157</a>] [<a href="https://doi.org/10.1007/BF00286520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6583157">1984</a>) found that enzyme activity cosegregated with chromosome 21. No enzyme activity was found in homocystinuric fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6583157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, <a href="#39" class="mim-tip-reference" title="Munke, M., Kraus, J., Watkins, P., Tanzi, R., Gusella, J., Millington Ward, A., Watson, M., Francke, U. <strong>Homocystinuria gene on human chromosome 21 mapped with cloned cystathionine beta-synthase probe and in situ hybridization of other chromosome 21 probes. (Abstract)</strong> Cytogenet. Cell Genet. 40: 706-707, 1985."None>Munke et al. (1985)</a> assigned the CBS locus to chromosome 21q22. Using a rat cDNA probe for in situ hybridization to structurally rearranged chromosomes 21, <a href="#38" class="mim-tip-reference" title="Munke, M., Kraus, J. P., Ohura, T., Francke, U. <strong>The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17.</strong> Am. J. Hum. Genet. 42: 550-559, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2894761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2894761</a>]" pmid="2894761">Munke et al. (1988)</a> assigned CBS to the subtelomeric region of band 21q22.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2894761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Chadefaux, B., Rethore, M. O., Raoul, O., Ceballos, I., Poissonnier, M., Gilgenkrantz, S., Allard, D. <strong>Cystathionine beta synthase: gene dosage effect in trisomy 21.</strong> Biochem. Biophys. Res. Commun. 128: 40-44, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3157380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3157380</a>] [<a href="https://doi.org/10.1016/0006-291x(85)91641-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3157380">Chadefaux et al. (1985)</a> demonstrated a dosage effect for CBS enzymatic activity in fibroblasts from patients trisomic for chromosome 21, and in cases of deletion and partial trisomy found levels of activity consistent with location of the CBS locus between 21q22.1 and 21q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3157380" 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="#38" class="mim-tip-reference" title="Munke, M., Kraus, J. P., Ohura, T., Francke, U. <strong>The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17.</strong> Am. J. Hum. Genet. 42: 550-559, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2894761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2894761</a>]" pmid="2894761">Munke et al. (1988)</a> mapped the mouse gene to the proximal half of chromosome 17 by Southern analysis of hamster-mouse somatic cell hybrid DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2894761" 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="#56" class="mim-tip-reference" title="Stubbs, L., Kraus, J., Lehrach, H. <strong>The alpha-A-crystallin and cystathionine beta-synthase genes are physically very closely linked in proximal mouse chromosome 17.</strong> Genomics 7: 284-288, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2347594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2347594</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90553-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2347594">Stubbs et al. (1990)</a> demonstrated that the murine equivalents of the CBS and CRYA1 (<a href="/entry/123580">123580</a>) genes are very closely situated on mouse chromosome 17 in a segment not larger than 130 kb. Most of the genes concentrated in band 21q22, which may be relevant to the phenotype of Down syndrome, are located on mouse chromosome 16 or mouse chromosome 10. The close physical linkage of the mouse equivalents of CBS and CRYA1, combined with data that localize closely flanking mouse markers to human chromosome 6, suggest that the human 21q22/mouse chromosome 17 conserved segment is of limited physical size and contains a small number of Down syndrome-related genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2347594" 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="Avramopoulos, D., Cox, T., Kraus, J. P., Chakravarti, A., Antonarakis, S. E. <strong>Linkage mapping of the cystathionine beta-synthase (CBS) gene on human chromosome 21 using a DNA polymorphism in the 3-prime untranslated region.</strong> Hum. Genet. 90: 566-568, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8094069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8094069</a>] [<a href="https://doi.org/10.1007/BF00217460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8094069">Avramopoulos et al. (1993)</a> used single-strand conformation polymorphism (SSCP) to detect DNA polymorphisms in the 3-prime untranslated region of the CBS gene. Using one of these for linkage studies in CEPH families, they placed the CBS gene on human chromosome 21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8094069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The human CBS protein can substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae (<a href="#32" class="mim-tip-reference" title="Kruger, W. D., Cox, D. R. <strong>A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes.</strong> Proc. Nat. Acad. Sci. 91: 6614-6618, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8022826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8022826</a>] [<a href="https://doi.org/10.1073/pnas.91.14.6614" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8022826">Kruger and Cox, 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8022826" 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>Heme may be necessary for binding of pyridoxal 5-prime phosphate to CBS and for correct CBS folding (<a href="#19" class="mim-tip-reference" title="Kery, V., Poneleit, L., Meyer, J. D., Manning, M. C., Kraus, J. P. <strong>Binding of pyridoxal 5-prime-phosphate to the heme protein human cystathionine beta-synthase.</strong> Biochemistry 38: 2716-2724, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10052942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10052942</a>] [<a href="https://doi.org/10.1021/bi981808n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10052942">Kery et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10052942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The catalytic domain of the CBS protein is located in the N-terminal 409 amino acids, and a regulatory domain is located in the C-terminal 142 amino acids. Using the Kruger-Cox yeast system for studying human CBS gene function, <a href="#48" class="mim-tip-reference" title="Shan, X., Kruger, W. D. <strong>Correction of disease-causing CBS mutations in yeast.</strong> Nature Genet. 19: 91-93, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590298</a>] [<a href="https://doi.org/10.1038/ng0598-91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590298">Shan and Kruger (1998)</a> reported that a mutation that deletes the C-terminal 145 amino acids of CBS could restore activity of several CBS mutant alleles found in homocystinurics. This C-terminal domain must thus act to inhibit enzymatic activity. In addition, the C-terminal domain is in turn regulated by S-adenosylmethionine (AdoMet), a positive effector of CBS. <a href="#48" class="mim-tip-reference" title="Shan, X., Kruger, W. D. <strong>Correction of disease-causing CBS mutations in yeast.</strong> Nature Genet. 19: 91-93, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590298</a>] [<a href="https://doi.org/10.1038/ng0598-91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590298">Shan and Kruger (1998)</a> suggested that most mutations in patients with homocystinuria do not cause dysfunction of the catalytic domain, but rather interfere with the activation of the enzyme. These findings suggested a new drug target to treat homocystinuria and homocysteine-related vascular disease. <a href="#47" class="mim-tip-reference" title="Shan, X., Dunbrack, R. L., Jr., Christopher, S. A., Kruger, W. D. <strong>Mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient-derived mutations in cis.</strong> Hum. Molec. Genet. 10: 635-643, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230183</a>] [<a href="https://doi.org/10.1093/hmg/10.6.635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11230183">Shan et al. (2001)</a> used a yeast genetic screen to identify missense mutations in the C-terminal region of CBS that could suppress the most common patient mutation, I278T (<a href="#0004">613381.0004</a>). Seven suppressor mutations were identified, 4 of which mapped to the C-terminal regulatory domain. When combined in cis with another pathogenic mutation, val168-to-met (V168M; <a href="#0011">613381.0011</a>), 6 of 7 of the suppressor mutations rescued the yeast phenotype. Enzyme activity analyses indicated that the suppressors restored activity from less than 2% to 17 to 64% of the wildtype levels. Analysis of the suppressor mutations in the absence of the pathogenic mutation showed that 6 of the 7 suppressor alleles had lost enzymatic responsiveness to S-adenosylmethionine. Using homology modeling, the suppressor mutations appeared to map on one face of the regulatory domain. The authors concluded that subtle changes to the C terminus of CBS may restore activity to mutant proteins, which could provide a rationale for screening for compounds that could activate mutant CBS alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9590298+11230183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The CBS gene on chromosome 21 is overexpressed in patients with trisomy 21 (<a href="/entry/190685">190685</a>). <a href="#41" class="mim-tip-reference" title="Pogribna, M., Melnyk, S., Pogribny, I., Chango, A., Yi, P., James, S. J. <strong>Homocysteine metabolism in children with Down syndrome: in vitro modulation.</strong> Am. J. Hum. Genet. 69: 88-95, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11391481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11391481</a>] [<a href="https://doi.org/10.1086/321262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11391481">Pogribna et al. (2001)</a> evaluated homocysteine metabolism in Down syndrome and sought to determine whether the supplementation of trisomy 21 lymphoblasts in vitro with selected nutrients would shift the genetically induced metabolic imbalance. They found that the increased activity of CBS in Down syndrome significantly alters homocysteine metabolism so that the folate-dependent resynthesis of methionine is compromised. The decreased availability of homocysteine promotes the well-established 'folate trap,' creating a functional folate deficiency that may contribute to the metabolic pathology of this complex genetic disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11391481" 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>CBS domains were originally identified as sequence motifs of approximately 60 amino acids that occur in cystathionine beta-synthase, and several other proteins, in all organisms from archaea to humans (<a href="#3" class="mim-tip-reference" title="Bateman, A. <strong>The structure of a domain common to archaebacteria and the homocystinuria disease protein.</strong> Trends Biochem. Sci. 22: 12-13, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020585</a>] [<a href="https://doi.org/10.1016/s0968-0004(96)30046-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9020585">Bateman, 1997</a>). Their functional importance was emphasized by findings that point mutations within them cause several hereditary diseases in humans, including homocystinuria. <a href="#44" class="mim-tip-reference" title="Scott, J. W., Hawley, S. A., Green, K. A., Anis, M., Stewart, G., Scullion, G. A., Norman, D. G., Hardie, D. G. <strong>CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.</strong> J. Clin. Invest. 113: 274-284, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722619</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722619[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/10.1172/JCI19874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722619">Scott et al. (2004)</a> showed that tandem pairs of CBS domains from AMP-activated protein kinase, IMP dehydrogenase-2 (IMPDH2; <a href="/entry/146691">146691</a>), the chloride channel CLC2 (<a href="/entry/600570">600570</a>), and cystathionine beta-synthase bind AMP, ATP, or S-adenosylmethionine, whereas mutations that cause hereditary diseases impair this binding. This showed that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a class of binding domain for adenosine derivatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9020585+14722619" 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="#30" class="mim-tip-reference" title="Kraus, J. P. <strong>Molecular basis of phenotype expression in homocystinuria.</strong> J. Inherit. Metab. Dis. 17: 383-390, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7967489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7967489</a>] [<a href="https://doi.org/10.1007/BF00711354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7967489">Kraus (1994)</a> tabulated 14 mutations in the CBS gene that he and his colleagues had demonstrated in homocystinuria (<a href="/entry/236200">236200</a>). The G307S mutation (<a href="#0001">613381.0001</a>) is the most common cause of homocystinuria in patients of Celtic origin. <a href="#30" class="mim-tip-reference" title="Kraus, J. P. <strong>Molecular basis of phenotype expression in homocystinuria.</strong> J. Inherit. Metab. Dis. 17: 383-390, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7967489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7967489</a>] [<a href="https://doi.org/10.1007/BF00711354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7967489">Kraus (1994)</a> indicated that even though patients have no measurable CBS activity in their fibroblasts and despite the fact that CBS subunits are undetectable in fibroblast extracts of some of these individuals, many of them are pyridoxine-responsive. Examples were cited in which the identical genotype resulted in a different phenotype within the family. In general, G307S is a pyridoxine-nonresponsive mutation, whereas I278T (<a href="#0004">613381.0004</a>) is a pyridoxine-responsive mutation (<a href="#16" class="mim-tip-reference" title="Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E. <strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong> Hum. Molec. Genet. 2: 1857-1860, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7506602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7506602</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7506602">Hu et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7506602+7967489" 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="#45" class="mim-tip-reference" title="Sebastio, G., Sperandeo, M. P., Panico, M., de Franchis, R., Kraus, J. P., Andria, G. <strong>The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.</strong> Am. J. Hum. Genet. 56: 1324-1333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762555</a>]" pmid="7762555">Sebastio et al. (1995)</a> identified a 68-bp insertion in exon 8 of the CBS gene (<a href="#0017">613381.0017</a>) in a patient with homocystinuria and predicted that it would introduce a premature termination codon and result in a nonfunctional CBS enzyme. However, <a href="#57" class="mim-tip-reference" title="Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q. <strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong> Am. J. Hum. Genet. 59: 1262-1267, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>]" pmid="8940271">Tsai et al. (1996)</a> found that this mutation is highly prevalent. In a case-control study involving patients with premature coronary artery disease, they identified the mutation in heterozygosity in 11.7% of controls and in slightly higher prevalence in the patients, although the difference did not reach statistical significance. In all cases, the insertion was present in cis with the 833T-C (I278T) mutation. <a href="#57" class="mim-tip-reference" title="Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q. <strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong> Am. J. Hum. Genet. 59: 1262-1267, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>]" pmid="8940271">Tsai et al. (1996)</a> suggested that the insertion created an alternate splicing site that eliminated not only the inserted intronic sequences, but also the 833T-C mutation associated with this insertion. The net result was the generation of both quantitatively and qualitatively normal mRNA and CBS enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7762555+8940271" 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="#27" class="mim-tip-reference" title="Kraus, J. P., Janosik, M., Kozich, V., Mandell, R., Shih, V., Sperandeo, M. P., Sebastio, G., de Franchis, R., Andria, G., Kluijtmans, L. A. J., Blom, H., Boers, G. H. J., Gordon, R. B., Kamoun, P., Tsai, M. Y., Kruger, W. D., Koch, H. G., Ohura, T., Gaustadnes, M. <strong>Cystathionine beta-synthase mutations in homocystinuria.</strong> Hum. Mutat. 13: 362-375, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10338090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10338090</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<362::AID-HUMU4>3.0.CO;2-K" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10338090">Kraus et al. (1999)</a> stated that 92 different disease-associated mutations of the CBS gene had been identified in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations were missense, and the vast majority of these were private mutations occurring in only 1 or a very small number of families. The 2 most frequently encountered mutations were the pyridoxine-responsive I278T (<a href="#0004">613381.0004</a>) and the pyridoxine-nonresponsive G307S (<a href="#0001">613381.0001</a>). Mutations due to deaminations of methylcytosines represented 53% of all point substitutions in the coding region of the CBS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10338090" 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="Janosik, M., Oliveriusova, J., Janosikova, B., Sokolova, J., Kraus, E., Kraus, J. P., Kozich, V. <strong>Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria.</strong> Am. J. Hum. Genet. 68: 1506-1513, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11359213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11359213</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11359213[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/10.1086/320597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11359213">Janosik et al. (2001)</a> reported observations suggesting that inability to bind heme may prevent correct folding and subsequent tetramer formation of mutant and, to a lesser extent, normal CBS subunits. They postulated that, as with other genetic defects (<a href="#5" class="mim-tip-reference" title="Bross, P., Corydon, T. J., Andresen, B. S., Jorgensen, M. M., Bolund, L., Gregersen, N. <strong>Protein misfolding and degradation in genetic diseases.</strong> Hum. Mutat. 14: 186-198, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477427</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<186::AID-HUMU2>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10477427">Bross et al., 1999</a>), mutant CBS misfolding and aggregation may be the primary defect in a significant proportion of patients with homocystinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10477427+11359213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 6 patients from 5 Korean families with homocystinuria, <a href="#36" class="mim-tip-reference" title="Lee, S.-J., Lee, D. H., Yoo, H.-W., Koo, S. K., Park, E.-S., Park, J.-W., Lim, H. G., Jung, S.-C. <strong>Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria.</strong> J. Hum. Genet. 50: 648-654, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205833</a>] [<a href="https://doi.org/10.1007/s10038-005-0312-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16205833">Lee et al. (2005)</a> identified 8 different mutations in the CBS gene, including 4 novel mutations. In vitro functional expression studies showed that the mutant enzymes had significantly decreased activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16205833" 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="#60" class="mim-tip-reference" title="Watanabe, M., Osada, J., Aratani, Y., Kluckman, K., Reddick, R., Malinow, M. R., Maeda, N. <strong>Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.</strong> Proc. Nat. Acad. Sci. 92: 1585-1589, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7878023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7878023</a>] [<a href="https://doi.org/10.1073/pnas.92.5.1585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7878023">Watanabe et al. (1995)</a> generated mice that were moderately and severely homocysteinemic, using homologous recombination in mouse embryonic stem cells to inactivate the Cbs gene. Homozygous mutants completely lacking cystathionine beta-synthase were born at the expected frequency from matings of heterozygotes, but they suffered from severe growth retardation and most of them died within 5 weeks after birth. Histologic examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets (resembling the finding in some severe homocystinuric patients). Plasma homocysteine levels of the homozygotes were approximately 40 times normal. Heterozygous mutants had approximately 50% reduction in CBS mRNA and enzyme activity in the liver and had twice normal plasma homocysteine levels. <a href="#60" class="mim-tip-reference" title="Watanabe, M., Osada, J., Aratani, Y., Kluckman, K., Reddick, R., Malinow, M. R., Maeda, N. <strong>Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.</strong> Proc. Nat. Acad. Sci. 92: 1585-1589, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7878023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7878023</a>] [<a href="https://doi.org/10.1073/pnas.92.5.1585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7878023">Watanabe et al. (1995)</a> concluded that homozygotes are a useful model for the clinical disorder homocystinuria and the heterozygotes should be useful for studying the role of elevated levels of homocysteine in the causation of cardiovascular disease. They noted that most of the homozygous mutant mice had eyes with delayed and narrow eye openings but without obvious histologic abnormalities. Seemingly, the homozygotes did not survive long enough to develop osteoporosis and vascular occlusions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7878023" 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="#42" class="mim-tip-reference" title="Robert, K., Chasse, J.-F., Santiard-Baron, D., Vayssettes, C., Chabli, A., Aupetit, J., Maeda, N., Kamoun, P., London, J., Janel, N. <strong>Altered gene expression in liver from a murine model of hyperhomocysteinemia.</strong> J. Biol. Chem. 278: 31504-31511, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12799373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12799373</a>] [<a href="https://doi.org/10.1074/jbc.M213036200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12799373">Robert et al. (2003)</a> found that Cbs-null mice fed a standard diet died before 1 month of age. Chow enriched with choline chloride allowed longer survival. Homocysteine was significantly increased in plasma and liver of Cbs-null mice compared to controls. Gene expression measured by Northern blot analysis showed altered expression of genes encoding ribosomal protein S3a (RPS3A; <a href="/entry/180478">180478</a>) and MTAP (<a href="/entry/156540">156540</a>), suggesting changes in cellular growth and proliferation. In addition, many up- or down-regulated genes indicated perturbations of the redox potential, including cytochromes P450 (see, e.g., <a href="/entry/107910">107910</a>), heme oxygenase 1 (HMOX1; <a href="/entry/141250">141250</a>), and PON1 (<a href="/entry/168820">168820</a>), suggesting increased oxidative stress in these animals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12799373" 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="#40" class="mim-tip-reference" title="Namekata, K., Enokido, Y., Ishii, I., Nagai, Y., Harada, T., Kimura, H. <strong>Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia.</strong> J. Biol. Chem. 279: 52961-52969, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15466479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15466479</a>] [<a href="https://doi.org/10.1074/jbc.M406820200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15466479">Namekata et al. (2004)</a> found that Cbs-null mice had abnormal lipid metabolism, with markedly increased triglyceride and nonesterified fatty acid levels in liver and serum. Thiolase activity was significantly impaired and hepatic apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and very low density lipoprotein levels were increased. Other findings included decreased activity of LCAT (<a href="/entry/606967">606967</a>) and altered serum cholesterol/triglyceride distribution in lipoprotein fractions. These findings suggested impaired beta-oxidation of fatty acids, and indicated that hepatic steatosis in Cbs-null mice is caused by or associated with abnormal lipid metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15466479" 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="#59" class="mim-tip-reference" title="Wang, L., Chen, X., Tang, B., Hua, X., Klein-Szanto, A., Kruger, W. D. <strong>Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model.</strong> Hum. Molec. Genet. 14: 2201-2208, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15972722[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972722">Wang et al. (2005)</a> engineered mice that expressed the common human mutant I278T and I278T/T424N Cbs proteins. These transgene-containing mice were then bred to Cbs +/- mice to generate Cbs -/- mice that expressed only the I278T or I278T/T424N human transgenes. Both the I278T and the I278T/T424N transgenes were able to entirely rescue the neonatal mortality phenotype of Cbs -/- mice (see <a href="#60" class="mim-tip-reference" title="Watanabe, M., Osada, J., Aratani, Y., Kluckman, K., Reddick, R., Malinow, M. R., Maeda, N. <strong>Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.</strong> Proc. Nat. Acad. Sci. 92: 1585-1589, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7878023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7878023</a>] [<a href="https://doi.org/10.1073/pnas.92.5.1585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7878023">Watanabe et al., 1995</a>) despite these mice having a mean homocysteine level of 250 micromols. The transgenic Cbs -/- animals exhibited facial alopecia, had moderate liver steatosis, and were slightly smaller than heterozygous littermates. In contrast to human CBS deficiency, these mice did not exhibit hypermethioninemia. The mutant proteins were stable in several tissues, although liver extracts had only 2 to 3% of the Cbs enzyme activity found in wildtype mice. The I278T/T424N enzyme had exactly the same activity as the I278T enzyme, indicating that T424N was unable to suppress I278T in mice. <a href="#59" class="mim-tip-reference" title="Wang, L., Chen, X., Tang, B., Hua, X., Klein-Szanto, A., Kruger, W. D. <strong>Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model.</strong> Hum. Molec. Genet. 14: 2201-2208, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15972722[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972722">Wang et al. (2005)</a> concluded that elevated homocysteine levels per se were not responsible for the neonatal lethality observed in Cbs -/- animals and suggested that CBS protein may have other functions in addition to its role in homocysteine catabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7878023+15972722" 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="#35" class="mim-tip-reference" title="Kruger, W. D. <strong>Cystathionine beta-synthase deficiency: of mice and men.</strong> Molec. Genet. Metab. 121: 199-205, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28583326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28583326</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28583326[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28583326">Kruger (2017)</a> reviewed mouse models of CBS deficiency that express either low levels of wildtype or mutant human CBS proteins. The models mimic the metabolic sequelae of the disease and present similar skeletal defects and body composition differences. They appear to be a good system for studying the effects of dietary alterations on these phenotypes. For example, mice on a low methionine diet, like treated human patients, show a significant reduction in homocysteine-related phenotypes. Vascular differences in these mice are not a major source of morbidity as they are in the human disease. Plaque rupture, for example, the main source of thrombotic events in humans, is almost never seen in these mice. A dislocated lens phenotype is not observed in these mouse models, and the pyridoxine responsiveness in humans is not replicated in these mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28583326" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Behera, J., Kelly, K. E., Voor, M. J., Metreveli, N., Tyagi, S. C., Tyagi, N. <strong>Hydrogen sulfide promotes bone homeostasis by balancing inflammatory cytokine signaling in CBS-deficient mice through an epigenetic mechanism.</strong> Sci. Rep. 8: 15226, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323246</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323246[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/10.1038/s41598-018-33149-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30323246">Behera et al. (2018)</a> found that Cbs +/- mice developed hyperhomocysteinemia (HHCY). Analysis of bone marrow mesenchymal stem cells (BMMSCs) from Cbs +/- mice showed that Cbs was essential for production of H2S, a gasotransmitter molecule that regulates bone formation. Administration of H2S ameliorated HHCY-induced redox homeostasis and prevented bone loss in Cbs +/- mice. Cbs deficiency-induced HHCY caused alternation of chromatin landscapes and inflammation by attenuating histone acetylation activity. Specifically, HHCY induced Nfkb (see <a href="/entry/164014">164014</a>) acetylation to promote histone acetylation-dependent proinflammatory signaling, which was ameliorated by administration of H2S in Cbs +/- mice. H2S induced osteogenic gene expression by suppressing histone acetylation-dependent Nfkb signaling activation and inflammation. In vitro analysis with Cbs +/- mouse BMMSCs revealed that HHCY induced secretion of inflammatory cytokines to upregulate osteoclastogenesis, but it was reversed by treatment with H2S. H2S promoted osteogenesis and was required for osteoblast biologic activity, including differentiation, maturation, and mineralization. In vivo analysis in Cbs +/- mice indicated that H2S was required for normal bone homeostasis and potentially mitigated Cbs deficiency-induced osteoporosis. As a result, H2S deficiency in Cbs +/- mice induced generation of reactive oxygen species (ROS) in BMMSCs and potentiated osteoporotic bone loss. Further analysis demonstrated that osteogenic marker Runx2 (<a href="/entry/600211">600211</a>) was sulfhydrated after H2S treatment and mediated osteogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30323246" 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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In 2 unrelated patients with homocystinuria (<a href="/entry/236200">236200</a>), <a href="#14" class="mim-tip-reference" title="Gu, Z., Ramesh, V., Kozich, V., Korson, M. S., Kraus, J. P., Shih, V. E. <strong>Identification of a molecular genetic defect in homocystinuria due to cystathionine beta-synthase deficiency. (Abstract)</strong> Am. J. Hum. Genet. 49: 406 only, 1991."None>Gu et al. (1991)</a> found a G-to-A transition in the CBS gene, resulting in a gly307-to-ser (G307S) substitution. Functional expression studies in E. coli showed a peptide of normal mobility that lacked CBS activity.</p><p><a href="#16" class="mim-tip-reference" title="Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E. <strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong> Hum. Molec. Genet. 2: 1857-1860, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7506602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7506602</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7506602">Hu et al. (1993)</a> found the G307S mutation in one allele of a patient of French/Scottish ancestry and in both alleles of a patient of Irish ancestry. Both parents of the second patient were heterozygotes for G307S. The mutant protein was apparently stable in expression studies in E. coli but lacked catalytic activity. Sequencing of exon 8 revealed the G307S mutation in 5 additional families. All had pyridoxine-nonresponsive homocystinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7506602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E. <strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong> Hum. Molec. Genet. 2: 1857-1860, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7506602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7506602</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7506602">Hu et al. (1993)</a> observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic backgrounds. All 9 were from patients with Celtic (Irish/English/Scottish/French) ancestry in either one or both parents. Indeed, the G307S mutation was detected in 9 of 18 Celtic alleles in their series. A second mutation found in exon 8 (I278T; <a href="#0004">613381.0004</a>) was associated with pyridoxine responsiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7506602" 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="Gallagher, P. M., Ward, P., Tan, S., Naughten, E., Kraus, J. P., Sellar, G. C., McConnell, D. J., Graham, I., Whitehead, A. S. <strong>High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.</strong> Hum. Mutat. 6: 177-180, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581402</a>] [<a href="https://doi.org/10.1002/humu.1380060211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581402">Gallagher et al. (1995)</a> analyzed 17 Irish unrelated persons with homocystinuria for the G307S mutation. Homozygosity for the mutation was found in 8 of the 17. A further 8 patients were compound heterozygotes, with the G307S mutation present on 1 allele. Of the 34 alleles, 24 (71%) were G307S. Screening of newborns for homocystinuria has been routine in Ireland since 1971. Newly diagnosed infants are also assessed for responsiveness to pyridoxine; all patients analyzed by <a href="#10" class="mim-tip-reference" title="Gallagher, P. M., Ward, P., Tan, S., Naughten, E., Kraus, J. P., Sellar, G. C., McConnell, D. J., Graham, I., Whitehead, A. S. <strong>High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.</strong> Hum. Mutat. 6: 177-180, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581402</a>] [<a href="https://doi.org/10.1002/humu.1380060211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581402">Gallagher et al. (1995)</a> were nonresponsive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581402" 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="#20" class="mim-tip-reference" title="Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D. <strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong> Hum. Molec. Genet. 6: 2213-2221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>] [<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9361025">Kim et al. (1997)</a> found a different distribution of CBS alleles in Norwegian cystinurics. The G307S mutation, which was found in 71% of mutant alleles in Ireland, accounted for only 20% in the Norwegian group and in Italian patients was not observed at all (<a href="#55" class="mim-tip-reference" title="Sperandeo, M. P., Panico, M., Pepe, A., Candito, M., de Franchis, R., Kraus, J. P., Andria, G., Sebastio, G. <strong>Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11.</strong> J. Inherit. Metab. Dis. 18: 211-214, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7564249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7564249</a>] [<a href="https://doi.org/10.1007/BF00711769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7564249">Sperandeo et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7564249+9361025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
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In a patient with early-onset stroke and hyperhomocysteinemia without other manifestations of classic homocystinuria (see <a href="/entry/236200">236200</a>), <a href="#18" class="mim-tip-reference" title="Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E. <strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong> Neurology 60: 275-279, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552044</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042479.55406.b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552044">Kelly et al. (2003)</a> identified a heterozygous G307S mutation. The patient was an 18-year-old Irish man with mitral valve prolapse who had an ischemic stroke. A second CBS mutation was not identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552044" 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> rs121964963 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964963;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/rs121964963?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=rs121964963" 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=rs121964963" 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=RCV000000139 OR RCV000625555 OR RCV001250193 OR RCV002227955" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000139, RCV000625555, RCV001250193, RCV002227955" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000139...</a>
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<p>In an adult female patient of Irish and German ancestry with relatively mild and late-onset signs of homocystinuria (<a href="/entry/236200">236200</a>) responsive to pyridoxine, <a href="#25" class="mim-tip-reference" title="Kozich, V., de Franchis, R., Kraus, J. P. <strong>Molecular defect in a patient with pyridoxine-responsive homocystinuria.</strong> Hum. Molec. Genet. 2: 815-816, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8353501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8353501</a>] [<a href="https://doi.org/10.1093/hmg/2.6.815" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8353501">Kozich et al. (1993)</a> found compound heterozygosity for 2 different mutations of the CBS gene: a 434C-T transition resulting in a pro145-to-leu (P145L) substitution, and a 341C-T transition resulting in an ala114-to-val (A114V; <a href="#0003">613381.0003</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8353501" 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> rs121964964 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964964;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/rs121964964?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=rs121964964" 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=rs121964964" 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=RCV000000140 OR RCV000200823 OR RCV000490533 OR RCV000590659 OR RCV002227956 OR RCV002453244 OR RCV003952330" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000140, RCV000200823, RCV000490533, RCV000590659, RCV002227956, RCV002453244, RCV003952330" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000140...</a>
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<p>For discussion of the ala114-to-val (A114V) mutation in the CBS gene that was found in compound heterozygous state in a patient with homocystinuria (<a href="/entry/236200">236200</a>) by <a href="#25" class="mim-tip-reference" title="Kozich, V., de Franchis, R., Kraus, J. P. <strong>Molecular defect in a patient with pyridoxine-responsive homocystinuria.</strong> Hum. Molec. Genet. 2: 815-816, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8353501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8353501</a>] [<a href="https://doi.org/10.1093/hmg/2.6.815" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8353501">Kozich et al. (1993)</a>, see <a href="/entry/613881#0002">613881.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8353501" 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> rs5742905 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs5742905;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/rs5742905?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=rs5742905" 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=rs5742905" 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=RCV000000141 OR RCV000000142 OR RCV000078111 OR RCV000173640 OR RCV000781197 OR RCV001252178 OR RCV002276525 OR RCV002310621 OR RCV003128384 OR RCV004584135" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000141, RCV000000142, RCV000078111, RCV000173640, RCV000781197, RCV001252178, RCV002276525, RCV002310621, RCV003128384, RCV004584135" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000141...</a>
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<p><strong><em>Homocystinuria</em></strong></p><p>
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On both alleles of a pyridoxine-responsive Polish patient with homocystinuria, <a href="#16" class="mim-tip-reference" title="Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E. <strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong> Hum. Molec. Genet. 2: 1857-1860, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7506602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7506602</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7506602">Hu et al. (1993)</a> identified an 833T-C transition in exon 8 of the CBS gene, resulting in an ile278-to-thr (I278T) substitution. They also identified this mutation on 1 allele of a pyridoxine-nonresponsive Polish patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7506602" 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 mildly affected pyridoxine-responsive patient of Ashkenazi Jewish origin, <a href="#26" class="mim-tip-reference" title="Kozich, V., Kraus, J. P. <strong>Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency.</strong> Hum. Mutat. 1: 113-123, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301198</a>] [<a href="https://doi.org/10.1002/humu.1380010206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301198">Kozich and Kraus (1992)</a> identified compound heterozygosity for a maternal I278T mutation and a paternal IVS11-2A-C mutation (<a href="#0012">613381.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By PCR amplification and sequencing of exon 8 from genomic DNA, <a href="#49" class="mim-tip-reference" title="Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V. <strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong> Am. J. Hum. Genet. 57: 34-39, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611293</a>]" pmid="7611293">Shih et al. (1995)</a> detected the I278T mutation in 7 of 11 patients with in vivo pyridoxine-responsiveness and in none of 27 pyridoxine-nonresponsive patients; 2 pyridoxine-responsive patients were homozygous and 5 were heterozygous for I278T. They further observed the I278T mutation in 9 (41%) of 22 independent alleles in pyridoxine-responsive patients of various ethnic backgrounds. In 2 of the compound heterozygotes, they identified novel mutations (G139R, <a href="#0005">613381.0005</a> and E144K, <a href="#0006">613381.0006</a>) on the other allele. The 2 patients who were homozygous for I278T had only ectopia lentis and mild bone demineralization. <a href="#49" class="mim-tip-reference" title="Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V. <strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong> Am. J. Hum. Genet. 57: 34-39, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611293</a>]" pmid="7611293">Shih et al. (1995)</a> concluded that compound heterozygous patients who have one copy of the I278T mutation are likely to retain some degree of pyridoxine responsiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7611293" 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>Although the 833T-C mutation is found in 50% of the CBS alleles in Dutch homozygous CBS-deficient patients, <a href="#24" class="mim-tip-reference" title="Kluijtmans, L. A. J., van den Heuvel, L. P. W. J., Boers, G. H. J., Frosst, P., Stevens, E. M. B., van Oost, B. A., den Heijer, M., Trijbels, F. J. M., Rozen, R., Blom, H. J. <strong>Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease.</strong> Am. J. Hum. Genet. 58: 35-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554066</a>]" pmid="8554066">Kluijtmans et al. (1996)</a> found it in none of 60 patients with premature cardiovascular disease. This led them to conclude that heterozygosity for CBS deficiency is not involved in premature cardiovascular disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554066" 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 study of 21 unrelated Dutch pedigrees, <a href="#22" class="mim-tip-reference" title="Kluijtmans, L. A. J., Boers, G. H. J., Kraus, J. P., van den Heuvel, L. P. W. J., Cruysberg, J. R. M., Trijbels, F. J. M., Blom, H. J. <strong>The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment.</strong> Am. J. Hum. Genet. 65: 59-67, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364517</a>] [<a href="https://doi.org/10.1086/302439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364517">Kluijtmans et al. (1999)</a> found that of 10 different mutations detected in the CBS gene, I278T was predominant, being present in 23 (55%) of 42 independent alleles. Homozygotes for this mutation tended to have higher homocysteine levels than those in patients with other genotypes, but similar clinical manifestations. I278T homozygotes responded more efficiently to homocysteine-lowering treatment. After 378 patient-years of treatment, only 2 vascular events were recorded; without treatment at least 30 would have been expected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The I278T mutation is the most frequent mutation in homocystinuria in Italy, where most cases are B6-responsive and the disorder has a total frequency of approximately 1 in 55,000 as compared with a frequency of 1 in 58,000 in the United States and 1 in 889,000 in Japan (<a href="#46" class="mim-tip-reference" title="Sebastio, G. <strong>Personal Communication.</strong> Padua, Italy 3/20/1997."None>Sebastio, 1997</a>).</p><p><a href="#11" class="mim-tip-reference" title="Gaustadnes, M., Ingerslev, J., Rutiger, N. <strong>Prevalence of congenital homocystinuria in Denmark. (Letter)</strong> New Eng. J. Med. 340: 1513 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10328723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10328723</a>] [<a href="https://doi.org/10.1056/NEJM199905133401915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10328723">Gaustadnes et al. (1999)</a> stated that the I278T mutation is geographically widespread. They determined the frequency of this mutation among Danish newborns by screening 500 consecutive Guthrie cards (specimens of infants' blood collected on filter paper). A surprisingly high prevalence of the 833T-C mutation was detected among newborns, suggesting that the incidence of homocystinuria due to homozygosity for this mutation may be at least 1 per 20,500 live births in Denmark. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10328723" 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 study of 11 families in the state of Georgia (USA), <a href="#34" class="mim-tip-reference" title="Kruger, W. D., Wang, L., Jhee, K. H., Singh, R. H., Elsas, L. J., II. <strong>Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.</strong> Hum. Mutat. 22: 434-441, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14635102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14635102</a>] [<a href="https://doi.org/10.1002/humu.10290" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14635102">Kruger et al. (2003)</a> found that the I278T and T353M (<a href="#0015">613381.0015</a>) mutations accounted for 45% of the mutant alleles. The T353M mutation, found exclusively in 4 African American patients, was associated with a B6-nonresponsive phenotype and detection by neonatal screening for hypermethioninemia. The I278T mutation was found exclusively in Caucasian patients and was associated with a B6-responsive phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14635102" 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 population-based study in Denmark, <a href="#50" class="mim-tip-reference" title="Skovby, F., Gaustadnes, M., Mudd, S. H. <strong>A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency.</strong> Molec. Genet. Metab. 99: 1-3, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19819175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19819175</a>] [<a href="https://doi.org/10.1016/j.ymgme.2009.09.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19819175">Skovby et al. (2010)</a> concluded that the predominant portion of individuals who are homozygous for the I278T mutation may be clinically unaffected or may only be ascertained after the third decade due to a thromboembolic event. These individuals do not have most of the clinical features of complete CBS deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19819175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
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In a patient with early-onset stroke and hyperhomocysteinemia without other classic features of homocystinuria (see <a href="/entry/236200">236200</a>), <a href="#18" class="mim-tip-reference" title="Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E. <strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong> Neurology 60: 275-279, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552044</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042479.55406.b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552044">Kelly et al. (2003)</a> identified a heterozygous I278T mutation. The patient was a 47-year-old white woman of northern European descent with a thrombus in the right internal carotid artery. <a href="#18" class="mim-tip-reference" title="Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E. <strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong> Neurology 60: 275-279, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552044</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042479.55406.b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552044">Kelly et al. (2003)</a> postulated that she might have another, unidentified CBS mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552044" 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> rs121964965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964965;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/rs121964965?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=rs121964965" 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=rs121964965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the gly139-to-arg (G139R) mutation in the CBS gene that was found in compound heterozygous state in patients with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>) by <a href="#49" class="mim-tip-reference" title="Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V. <strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong> Am. J. Hum. Genet. 57: 34-39, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611293</a>]" pmid="7611293">Shih et al. (1995)</a>, see <a href="#0004">613381.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7611293" 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> rs121964966 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964966;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/rs121964966?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=rs121964966" 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=rs121964966" 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=RCV000000144 OR RCV000169074 OR RCV000723427 OR RCV001251284 OR RCV002227957 OR RCV003415595" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000144, RCV000169074, RCV000723427, RCV001251284, RCV002227957, RCV003415595" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000144...</a>
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<p>For discussion of the glu144-to-lys (E144K) mutation in the CBS gene that was found in compound heterozygous state in patients with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>) by <a href="#49" class="mim-tip-reference" title="Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V. <strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong> Am. J. Hum. Genet. 57: 34-39, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611293</a>]" pmid="7611293">Shih et al. (1995)</a>, see <a href="#0004">613381.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7611293" 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">rs121964967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964967;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=rs121964967" 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=rs121964967" 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=RCV000000145 OR RCV003495103" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000145, RCV003495103" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000145...</a>
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<p>In 2 unrelated French vitamin B6-responsive homocystinuria (<a href="/entry/236200">236200</a>) patients with no Celtic origin, <a href="#1" class="mim-tip-reference" title="Aral, B., Coude, M., London, J., Aupetit, J., Chasse, J.-F., Zabot, M.-T., Chadefaux-Vekemans, B., Kamoun, P. <strong>Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients.</strong> Hum. Mutat. 9: 81-82, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990018</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<81::AID-HUMU18>3.0.CO;2-L" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8990018">Aral et al. (1997)</a> demonstrated novel mutations in the CBS gene. One patient had unilateral lens subluxation and deep vein thrombosis at age 6, and a Marfan-like appearance with thinning of long bones and digits, together with osteoporosis of the lower limbs. This patient was homozygous for a 1150A-G transition, resulting in a substitution lys384-to-glu (K384E). See also <a href="#0008">613381.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8990018" 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>.0008 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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">rs121964968 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964968;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=rs121964968" 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=rs121964968" 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=RCV000000146 OR RCV000675072 OR RCV002468955 OR RCV003597960" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000146, RCV000675072, RCV002468955, RCV003597960" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000146...</a>
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<p>In a patient with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>), <a href="#1" class="mim-tip-reference" title="Aral, B., Coude, M., London, J., Aupetit, J., Chasse, J.-F., Zabot, M.-T., Chadefaux-Vekemans, B., Kamoun, P. <strong>Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients.</strong> Hum. Mutat. 9: 81-82, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990018</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<81::AID-HUMU18>3.0.CO;2-L" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8990018">Aral et al. (1997)</a> demonstrated homozygosity for a leu539-to-ser (L539S) mutation in the CBS gene. See also <a href="#0007">613381.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8990018" 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 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</strong>
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CBS, ARG266LYS
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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> rs121964969 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964969;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/rs121964969?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=rs121964969" 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=rs121964969" 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=RCV000000147 OR RCV000469164 OR RCV001192721 OR RCV001546787 OR RCV002227958 OR RCV002313702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000147, RCV000469164, RCV001192721, RCV001546787, RCV002227958, RCV002313702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000147...</a>
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<p><a href="#20" class="mim-tip-reference" title="Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D. <strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong> Hum. Molec. Genet. 6: 2213-2221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>] [<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9361025">Kim et al. (1997)</a> found that 5 of 7 Norwegian patients classified as having pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>) had a 797G-A transition in the CBS gene, resulting in an arg266-to-lys (R266K) substitution. <a href="#20" class="mim-tip-reference" title="Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D. <strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong> Hum. Molec. Genet. 6: 2213-2221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>] [<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9361025">Kim et al. (1997)</a> tested the effect of all the mutations identified on human CBS function utilizing a yeast system. Five of the 6 mutations had a distinguishable phenotype in yeast, indicating that they were, in fact, pathogenic. The 797G-A had no phenotype when the yeast were grown in high concentrations of pyridoxine, but a severe phenotype when grown in low concentrations, thus mirroring the behavior in humans. The yeast functional assay was suggested as a guide to therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9361025" 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>.0010 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</strong>
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HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, INCLUDED
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CBS, ASP444ASN
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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> rs28934891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28934891;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/rs28934891?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=rs28934891" 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=rs28934891" 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=RCV000000148 OR RCV000000149 OR RCV000078108 OR RCV000174656 OR RCV000781196 OR RCV002381232 OR RCV004754226" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000148, RCV000000149, RCV000078108, RCV000174656, RCV000781196, RCV002381232, RCV004754226" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000148...</a>
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<p><strong><em>Homocystinuria</em></strong></p><p>
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In a 20-year-old woman with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>), <a href="#23" class="mim-tip-reference" title="Kluijtmans, L. A. J., Boers, G. H. J., Stevens, E. M. B., Renier, W. O., Kraus, J. P., Trijbels, F. J. M., van den Heuvel, L. P. W. J., Blom, H. J. <strong>Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient.</strong> J. Clin. Invest. 98: 285-289, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755636</a>] [<a href="https://doi.org/10.1172/JCI118791" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8755636">Kluijtmans et al. (1996)</a> identified a homozygous 1330G-A transition in the CBS gene, resulting in an asp444-to-asn (D444N) substitution in the regulatory domain of the protein. She was first admitted to the hospital at the age of 9 years because of psychomotor retardation, marfanoid features with excessive height, dolichostenomelia, arachnodactyly, and homocystinuria. She was treated with pyridoxine, folic acid, and betaine, with favorable results. Eleven years later she was in very good physical condition and her intellectual development had reached an average level. Ectopia lentis, osteoporosis, and vascular complications had not occurred. Both parents and an unaffected sister were heterozygous for the mutation. Despite the homozygous mutation, CBS activities in extracts of cultured fibroblasts of this patient were not in the homozygous but in the heterozygous range. In vitro functional expression studies showed no stimulation of CBS activity by S-adenosylmethionine, contrary to a 3-fold stimulation in control fibroblast extract. These data suggested that the D444N mutation interfered with S-adenosylmethionine regulation of CBS. Furthermore, it indicated the importance of S-adenosylmethionine regulation of the transsulfuration pathway in homocysteine homeostasis in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755636" 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>CBS domains are defined as sequence motifs that occur in several different proteins in all kingdoms of life. Their functional importance is underlined by the finding that mutations in conserved residues within them cause a variety of human hereditary diseases, including homocystinuria. <a href="#44" class="mim-tip-reference" title="Scott, J. W., Hawley, S. A., Green, K. A., Anis, M., Stewart, G., Scullion, G. A., Norman, D. G., Hardie, D. G. <strong>CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.</strong> J. Clin. Invest. 113: 274-284, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722619</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722619[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/10.1172/JCI19874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722619">Scott et al. (2004)</a> showed that tandem pairs of CBS domains from cystathionine beta-synthase, as well as the CBS domains from at least 3 other proteins that are the sites of mutations causing hereditary diseases, bind AMP, ATP, or S-adenosylmethionine, whereas mutations that cause hereditary diseases impair this binding. An interesting feature of the pathogenic mutations in CBS domains is that they tend to occur in equivalent positions. Thus, 3 mutations in the PRKAG2 gene that cause disease--R302Q (<a href="/entry/602743#0001">602743.0001</a>), H383R, and R531G (<a href="/entry/602743#0006">602743.0006</a>)--all align (plus or minus 1 residue) with the D444N mutation in the CBS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
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In a patient with early-onset stroke and hyperhomocysteinemia without other manifestations of homocystinuria (see <a href="/entry/236200">236200</a>), <a href="#18" class="mim-tip-reference" title="Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E. <strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong> Neurology 60: 275-279, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552044</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042479.55406.b3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552044">Kelly et al. (2003)</a> identified a heterozygous D444N mutation. The patient was a 39-year-old Venezuelan man who had a retinal artery occlusion due to an arterial dissection. An unaffected sister was also heterozygous for the mutation. The presence of a second mutation could not be excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552044" 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>.0011 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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"><span class="text-primary">●</span> rs121964970 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964970;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/rs121964970?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=rs121964970" 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=rs121964970" 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=RCV000000150 OR RCV000179250 OR RCV000458159 OR RCV002227959 OR RCV002265542 OR RCV002310622" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000150, RCV000179250, RCV000458159, RCV002227959, RCV002265542, RCV002310622" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000150...</a>
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<p>In a cell line from a patient with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>), <a href="#33" class="mim-tip-reference" title="Kruger, W. D., Cox, D. R. <strong>A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.</strong> Hum. Molec. Genet. 4: 1155-1161, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528202</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528202">Kruger and Cox (1995)</a> identified a 502G-A transition in the CBS gene, resulting in a val168-to-met (V168M) substitution in the catalytic domain. <a href="#47" class="mim-tip-reference" title="Shan, X., Dunbrack, R. L., Jr., Christopher, S. A., Kruger, W. D. <strong>Mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient-derived mutations in cis.</strong> Hum. Molec. Genet. 10: 635-643, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230183</a>] [<a href="https://doi.org/10.1093/hmg/10.6.635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11230183">Shan et al. (2001)</a> identified 7 mutations that could suppress the most common CBS patient mutation, I278T (<a href="#0004">613381.0004</a>), 4 of which mapped to the C-terminal regulatory domain. The suppressors, in combination with the V168M mutation, also expressed a full-length protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528202+11230183" 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>.0012 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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"><span class="text-primary">●</span> rs375846341 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs375846341;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/rs375846341?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=rs375846341" 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=rs375846341" 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=RCV000000151 OR RCV000174658 OR RCV000198380 OR RCV000590542 OR RCV002227960 OR RCV002354142 OR RCV003944786" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000151, RCV000174658, RCV000198380, RCV000590542, RCV002227960, RCV002354142, RCV003944786" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000151...</a>
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<p>In a mildly affected patient of Ashkenazi Jewish origin with pyridoxine-responsive homocystinuria (<a href="/entry/236200">236200</a>), <a href="#26" class="mim-tip-reference" title="Kozich, V., Kraus, J. P. <strong>Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency.</strong> Hum. Mutat. 1: 113-123, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301198</a>] [<a href="https://doi.org/10.1002/humu.1380010206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301198">Kozich and Kraus (1992)</a> identified compound heterozygosity for a maternal I278T mutation (<a href="#0004">613381.0004</a>) and a paternal A-to-C transversion in the intron 11 splice acceptor. The latter mutation led to an in-frame deletion of exon 12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301198" 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>.0013 HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED</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"><span class="text-primary">●</span> rs28934892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28934892;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/rs28934892?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=rs28934892" 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=rs28934892" 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=RCV000000152 OR RCV000522394 OR RCV000675050 OR RCV002444412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000152, RCV000522394, RCV000675050, RCV002444412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000152...</a>
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<p>In a group of unrelated patients that were screened for elevated homocysteine after an idiopathic thrombotic event (see <a href="/entry/236200">236200</a>), <a href="#12" class="mim-tip-reference" title="Gaustadnes, M., Rudiger, N., Rasmussen, K., Ingerslev, J. <strong>Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.</strong> Thromb. Haemost. 83: 554-558, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780316</a>]" pmid="10780316">Gaustadnes et al. (2000)</a> found that 1 was compound heterozygous for 2 mutations in the CBS gene: a pro422-to-leu substitution in the C-terminal regulatory domain, and an asp444-to-asn mutation (<a href="#0010">613381.0010</a>). The diagnosis of elevated homocysteine had been made after an episodic transient ischemic attack at the age of 22 years. The patient was found to be nonresponsive to therapy with either pyridoxine or betaine. The patient did not carry the 677C-T transition in the MTHFR gene (<a href="/entry/607093#0003">607093.0003</a>). The usual manifestations of classic homocystinuria such as ectopia lentis, marfanoid skeletal features, and mental retardation were lacking. In vitro functional expression studies showed that the P422L mutant protein was catalytically active and even had higher activity than wildtype, but was impaired in regulation by AdoMet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10780316" 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="0014" class="mim-anchor"></a>
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<h4>
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<strong>.0014 HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED</strong>
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CBS, SER466LEU
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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> rs121964971 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964971;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/rs121964971?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=rs121964971" 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=rs121964971" 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=RCV000000153 OR RCV000675119 OR RCV002390082 OR RCV003226154" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000153, RCV000675119, RCV002390082, RCV003226154" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000153...</a>
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<p>In a 39-year-old woman with high homocysteine levels when screened after an episodic transient ischemic attack at the age of 36 years (see <a href="/entry/236200">236200</a>) (<a href="#12" class="mim-tip-reference" title="Gaustadnes, M., Rudiger, N., Rasmussen, K., Ingerslev, J. <strong>Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.</strong> Thromb. Haemost. 83: 554-558, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780316</a>]" pmid="10780316">Gaustadnes et al., 2000</a>), <a href="#37" class="mim-tip-reference" title="Maclean, K. N., Gaustadnes, M., Oliveriusova, J., Janosik, M., Kraus, E., Kozich, V., Kery, V., Skovby, F., Rudiger, N., Ingerslev, J., Stabler, S. P., Allen, R. H., Kraus, J. P. <strong>High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations.</strong> Hum. Mutat. 19: 641-655, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12007221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12007221</a>] [<a href="https://doi.org/10.1002/humu.10089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12007221">Maclean et al. (2002)</a> found compound heterozygosity for 2 mutations in the CBS gene: I278T (<a href="#0004">613381.0004</a>) and a 139C-T transition, resulting in a ser466-to-leu (S466L) substitution in the C-terminal regulatory domain. The patient had no ectopia lentis, mental retardation, marfanoid skeletal features, or other characteristic features of classic homocystinuria (<a href="/entry/236200">236200</a>). In vitro functional expression studies showed that the S466L mutant protein was catalytically active and even had higher activity than wildtype, but was impaired in regulation by AdoMet. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10780316+12007221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Gupta, S., Wang, L., Hua, X., Krijt, J., Kozich, V., Kruger, W. D. <strong>Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice.</strong> Hum. Mutat. 29: 1048-1054, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18454451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18454451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18454451[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.20773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18454451">Gupta et al. (2008)</a> demonstrated that the S466L mutation in mice causes homocystinuria by affecting both the steady-state level of CBS and by reducing the efficiency of the enzyme. In the presence of zinc, the mean serum total homocysteine of transgenic S466L mice was 142(+/-55) microM compared to 16(+/-13) microM for wildtype. Transgenic mice also had significantly higher levels of total free homocysteine and S-adenosylhomocysteine in liver and kidney. Only 48% of S466L mice had detectable CBS protein in the liver, whereas all the wildtype animals had detectable protein. However, CBS mRNA was significantly elevated in transgenic mice, suggesting that the reduction in mutant protein resulted from posttranscriptional mechanisms. The mutant enzyme formed tetramers and was active, but lacked inducibility by S-adenosylmethionine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18454451" 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>.0015 HOMOCYSTINURIA, PYRIDOXINE-NONRESPONSIVE</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"><span class="text-primary">●</span> rs121964972 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964972;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/rs121964972?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=rs121964972" 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=rs121964972" 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=RCV000000154 OR RCV000078106 OR RCV000169466 OR RCV002227961 OR RCV002271361 OR RCV004018522" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000154, RCV000078106, RCV000169466, RCV002227961, RCV002271361, RCV004018522" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000154...</a>
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<p>In the state of Georgia (USA), <a href="#34" class="mim-tip-reference" title="Kruger, W. D., Wang, L., Jhee, K. H., Singh, R. H., Elsas, L. J., II. <strong>Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.</strong> Hum. Mutat. 22: 434-441, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14635102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14635102</a>] [<a href="https://doi.org/10.1002/humu.10290" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14635102">Kruger et al. (2003)</a> studied 11 families with CBS deficiency (<a href="/entry/236200">236200</a>). A thr353-to-met (T353M) mutation, found exclusively in 4 African American patients, was associated with a B6-nonresponsive phenotype and with detection by newborn screening for hypermethioninemia. The I278T (<a href="#0004">613381.0004</a>) and T353M mutations accounted for 45% of the mutant alleles in the affected members of the 11 families. The I278T mutation was found exclusively in Caucasian patients and was associated with a B6-responsive phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14635102" 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>.0016 HOMOCYSTINURIA, PYRIDOXINE-NONRESPONSIVE</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"><span class="text-primary">●</span> rs121964973 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964973;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/rs121964973?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=rs121964973" 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=rs121964973" 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=RCV000000155 OR RCV000195441 OR RCV000576767 OR RCV000589097 OR RCV002227962 OR RCV003914787 OR RCV004018523" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000155, RCV000195441, RCV000576767, RCV000589097, RCV002227962, RCV003914787, RCV004018523" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000155...</a>
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<p>Among 35 patients from 30 pedigrees with homocystinuria (<a href="/entry/236200">236200</a>) from the Iberian peninsula and several South American countries, <a href="#58" class="mim-tip-reference" title="Urreizti, R., Asteggiano, C., Bermudez, M., Cordoba, A., Szlago, M., Grosso, C., de Kremer, R. D., Vilarinho, L., D'Almeida, V., Martinez-Pardo, M., Pena-Quintana, L., Dalmau, J., Bernal, J., Briceno, I., Couce, M. L., Rodes, M., Vilaseca, M. A., Balcells, S., Grinberg, D. <strong>The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.</strong> J. Hum. Genet. 51: 305-313, 2006. Note: Erratum: J. Hum. Genet. 52: 388-389, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16479318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16479318</a>] [<a href="https://doi.org/10.1007/s10038-006-0362-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16479318">Urreizti et al. (2006)</a> found a high frequency of a 572C-T transition in the CBS gene, resulting in a thr191-to-met (T191M) substitution. The patients were from Spain, Portugal, Colombia, and Argentina. Combined with previously reported studies, the prevalence of T191M among mutant CBS alleles in different countries was 0.75 in Colombia, 0.52 in Spain, 0.33 in Portugal, 0.25 in Venezuela, 0.20 in Argentina, and 0.14 in Brazil. Haplotype analysis suggested a double origin for this mutation. The phenotype was B6-nonresponsive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16479318" 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><div class="mim-changed mim-change">.0017 CBS POLYMORPHISM</div></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000222887 OR RCV000990351 OR RCV001573597 OR RCV002225098 OR RCV002229201 OR RCV004020589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000222887, RCV000990351, RCV001573597, RCV002225098, RCV002229201, RCV004020589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000222887...</a>
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<p><a href="#45" class="mim-tip-reference" title="Sebastio, G., Sperandeo, M. P., Panico, M., de Franchis, R., Kraus, J. P., Andria, G. <strong>The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.</strong> Am. J. Hum. Genet. 56: 1324-1333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762555</a>]" pmid="7762555">Sebastio et al. (1995)</a> identified a 68-bp insertion in exon 8 of the CBS gene in a patient with homocystinuria and predicted that it would introduce a premature termination codon and result in a nonfunctional CBS enzyme. However, <a href="#57" class="mim-tip-reference" title="Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q. <strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong> Am. J. Hum. Genet. 59: 1262-1267, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>]" pmid="8940271">Tsai et al. (1996)</a> found that this mutation is highly prevalent. In a case-control study involving patients with premature coronary artery disease, they identified the mutation in heterozygosity in 11.7% of controls and in slightly higher prevalence in the patients, although the difference did not reach statistical significance. In all cases, the insertion was present in cis with the 833T-C (I278T; <a href="#0004">613381.0004</a>) mutation. <a href="#57" class="mim-tip-reference" title="Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q. <strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong> Am. J. Hum. Genet. 59: 1262-1267, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>]" pmid="8940271">Tsai et al. (1996)</a> suggested that the insertion created an alternate splicing site that eliminated not only the inserted intronic sequences, but also the 833T-C mutation associated with this insertion. The net result was the generation of both quantitatively and qualitatively normal mRNA and CBS enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7762555+8940271" 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="mim-changed mim-change"><p><a href="#54" class="mim-tip-reference" title="Sperandeo, M. P., de Franchis, R., Andria, G., Sebastio, G. <strong>A 68-bp insertion found in a homocystinuric patient is a common variant and is skipped by alternative splicing of the cystathionine beta-synthase mRNA. (Letter)</strong> Am. J. Hum. Genet. 59: 1391-1393, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940285</a>]" pmid="8940285">Sperandeo et al. (1996)</a> identified the 68-bp insertion as a benign polymorphism in an Italian cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940285" 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></div>
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<p><a href="#20" class="mim-tip-reference" title="Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D. <strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong> Hum. Molec. Genet. 6: 2213-2221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>] [<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9361025">Kim et al. (1997)</a> studied the mutations in 10 Norwegian CBS-deficient families and identified 18 of the 20 mutant alleles. In 9 of the 20 CBS alleles (45%), they found the 68-bp duplication allele. This frequency was much higher than the 6% reported by <a href="#57" class="mim-tip-reference" title="Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q. <strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong> Am. J. Hum. Genet. 59: 1262-1267, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>]" pmid="8940271">Tsai et al. (1996)</a> in a study population from the upper midwest of the US. In unaffected Norwegian chromosomes, <a href="#20" class="mim-tip-reference" title="Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D. <strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong> Hum. Molec. Genet. 6: 2213-2221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>] [<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9361025">Kim et al. (1997)</a> found the frequency of the duplication to be approximately 5.5% (2 in 36). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940271+9361025" 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="#9" class="mim-tip-reference" title="Franco, R. F., Elion, J., Lavinha, J., Krishnamoorthy, R., Tavella, M. H., Zago, M. A. <strong>Heterogeneous ethnic distribution of the 844ins68 in the cystathionine beta-synthase gene.</strong> Hum. Hered. 48: 338-342, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9813456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9813456</a>] [<a href="https://doi.org/10.1159/000022826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9813456">Franco et al. (1998)</a>, who referred to the 68-bp insertion in the coding region of exon 8 of the CBS gene as 844ins68, investigated its prevalence in 405 persons belonging to 4 different ethnic groups. The insertion was found in heterozygous state in 14 of 104 whites (13.5%), was absent among Asians, and was found in only 1 of 220 Amerindian chromosomes analyzed, whereas a much higher prevalence was observed among blacks (37.7% of heterozygotes and 4% of mutant homozygotes). In all carriers of the insertion, the 833T-C CBS mutation cosegregated in cis with 844ins68. The finding of the double mutant among blacks and Caucasians suggested that it antedated the divergence between Africans and non-Africans, and provided evidence for a partly or completely neutralizing effect conferred by the 68-bp insertion, since it allows the skipping of the 833T-C mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9813456" 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="#Goldstein1972" class="mim-tip-reference" title="Goldstein, J. L., Campbell, B. K., Gartler, S. M. <strong>Cystathionine synthetase activity in human lymphocytes: induction by phytohemagglutinin.</strong> J. Clin. Invest. 51: 1034-1037, 1972.">Goldstein et al. (1972)</a>; <a href="#Kim1974" class="mim-tip-reference" title="Kim, Y. J., Rosenberg, L. E. <strong>On the mechanism of pyridoxine responsive homocystinuria. II. Properties of normal and mutant cystathionine beta-synthase from cultured fibroblasts.</strong> Proc. Nat. Acad. Sci. 71: 4821-4825, 1974.">Kim and Rosenberg (1974)</a>; <a href="#Kraus1978" class="mim-tip-reference" title="Kraus, J., Packman, S., Fowler, B., Rosenberg, L. E. <strong>Purification and properties of cystathionine beta-synthase from human liver: evidence for identical subunits.</strong> J. Biol. Chem. 253: 6523-6528, 1978.">Kraus et al.
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(1978)</a>; <a href="#Skovby1984" class="mim-tip-reference" title="Skovby, F., Kraus, J. P., Rosenberg, L. E. <strong>Homocystinuria: biogenesis of cystathionine beta-synthase subunits in cultured fibroblasts and in an in vitro translation system programmed with fibroblast messenger RNA.</strong> Am. J. Hum. Genet. 36: 452-459, 1984.">Skovby et al. (1984)</a>
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Aral, B., Coude, M., London, J., Aupetit, J., Chasse, J.-F., Zabot, M.-T., Chadefaux-Vekemans, B., Kamoun, P.
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<strong>Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients.</strong>
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Hum. Mutat. 9: 81-82, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8990018" 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)1098-1004(1997)9:1<81::AID-HUMU18>3.0.CO;2-L" target="_blank">Full Text</a>]
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Avramopoulos, D., Cox, T., Kraus, J. P., Chakravarti, A., Antonarakis, S. E.
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<strong>Linkage mapping of the cystathionine beta-synthase (CBS) gene on human chromosome 21 using a DNA polymorphism in the 3-prime untranslated region.</strong>
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Hum. Genet. 90: 566-568, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8094069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8094069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8094069" 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/BF00217460" target="_blank">Full Text</a>]
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<a id="Bateman1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bateman, A.
|
|
<strong>The structure of a domain common to archaebacteria and the homocystinuria disease protein.</strong>
|
|
Trends Biochem. Sci. 22: 12-13, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9020585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0968-0004(96)30046-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Behera2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Behera, J., Kelly, K. E., Voor, M. J., Metreveli, N., Tyagi, S. C., Tyagi, N.
|
|
<strong>Hydrogen sulfide promotes bone homeostasis by balancing inflammatory cytokine signaling in CBS-deficient mice through an epigenetic mechanism.</strong>
|
|
Sci. Rep. 8: 15226, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323246</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323246[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=30323246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41598-018-33149-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bross1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bross, P., Corydon, T. J., Andresen, B. S., Jorgensen, M. M., Bolund, L., Gregersen, N.
|
|
<strong>Protein misfolding and degradation in genetic diseases.</strong>
|
|
Hum. Mutat. 14: 186-198, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<186::AID-HUMU2>3.0.CO;2-J" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Chadefaux1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chadefaux, B., Rethore, M. O., Raoul, O., Ceballos, I., Poissonnier, M., Gilgenkrantz, S., Allard, D.
|
|
<strong>Cystathionine beta synthase: gene dosage effect in trisomy 21.</strong>
|
|
Biochem. Biophys. Res. Commun. 128: 40-44, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3157380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3157380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3157380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(85)91641-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Chasse1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chasse, J. F., Paly, E., Paris, D., Paul, V., Sinet, P. M., Kamoun, P., London, J.
|
|
<strong>Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs.</strong>
|
|
Biochem. Biophys. Res. Commun. 211: 826-832, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7598711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7598711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7598711" 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/bbrc.1995.1886" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Chasse1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chasse, J. F., Paul, V., Escanez, R., Kamoun, P., London, J.
|
|
<strong>Human cystathionine beta-synthase: gene organization and expression of different 5-prime alternative splicing.</strong>
|
|
Mammalian Genome 8: 917-921, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9383285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9383285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9383285" 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/s003359900611" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Franco1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Franco, R. F., Elion, J., Lavinha, J., Krishnamoorthy, R., Tavella, M. H., Zago, M. A.
|
|
<strong>Heterogeneous ethnic distribution of the 844ins68 in the cystathionine beta-synthase gene.</strong>
|
|
Hum. Hered. 48: 338-342, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9813456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9813456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9813456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000022826" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Gallagher1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gallagher, P. M., Ward, P., Tan, S., Naughten, E., Kraus, J. P., Sellar, G. C., McConnell, D. J., Graham, I., Whitehead, A. S.
|
|
<strong>High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.</strong>
|
|
Hum. Mutat. 6: 177-180, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380060211" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gaustadnes1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaustadnes, M., Ingerslev, J., Rutiger, N.
|
|
<strong>Prevalence of congenital homocystinuria in Denmark. (Letter)</strong>
|
|
New Eng. J. Med. 340: 1513 only, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10328723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10328723</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10328723" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199905133401915" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gaustadnes2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaustadnes, M., Rudiger, N., Rasmussen, K., Ingerslev, J.
|
|
<strong>Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.</strong>
|
|
Thromb. Haemost. 83: 554-558, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10780316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Goldstein1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldstein, J. L., Campbell, B. K., Gartler, S. M.
|
|
<strong>Cystathionine synthetase activity in human lymphocytes: induction by phytohemagglutinin.</strong>
|
|
J. Clin. Invest. 51: 1034-1037, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5014609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5014609</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5014609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI106863" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gu1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gu, Z., Ramesh, V., Kozich, V., Korson, M. S., Kraus, J. P., Shih, V. E.
|
|
<strong>Identification of a molecular genetic defect in homocystinuria due to cystathionine beta-synthase deficiency. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49: 406 only, 1991.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Gupta2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gupta, S., Wang, L., Hua, X., Krijt, J., Kozich, V., Kruger, W. D.
|
|
<strong>Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice.</strong>
|
|
Hum. Mutat. 29: 1048-1054, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18454451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18454451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18454451[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=18454451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20773" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Hu1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E.
|
|
<strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong>
|
|
Hum. Molec. Genet. 2: 1857-1860, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7506602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7506602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7506602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/2.11.1857" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Janosik2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janosik, M., Oliveriusova, J., Janosikova, B., Sokolova, J., Kraus, E., Kraus, J. P., Kozich, V.
|
|
<strong>Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria.</strong>
|
|
Am. J. Hum. Genet. 68: 1506-1513, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11359213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11359213</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11359213[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=11359213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/320597" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kelly2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E.
|
|
<strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong>
|
|
Neurology 60: 275-279, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000042479.55406.b3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kery1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kery, V., Poneleit, L., Meyer, J. D., Manning, M. C., Kraus, J. P.
|
|
<strong>Binding of pyridoxal 5-prime-phosphate to the heme protein human cystathionine beta-synthase.</strong>
|
|
Biochemistry 38: 2716-2724, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10052942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10052942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10052942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi981808n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Kim1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D.
|
|
<strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong>
|
|
Hum. Molec. Genet. 6: 2213-2221, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9361025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9361025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9361025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.13.2213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Kim1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, Y. J., Rosenberg, L. E.
|
|
<strong>On the mechanism of pyridoxine responsive homocystinuria. II. Properties of normal and mutant cystathionine beta-synthase from cultured fibroblasts.</strong>
|
|
Proc. Nat. Acad. Sci. 71: 4821-4825, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4531018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4531018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4531018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.71.12.4821" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Kluijtmans1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., Boers, G. H. J., Kraus, J. P., van den Heuvel, L. P. W. J., Cruysberg, J. R. M., Trijbels, F. J. M., Blom, H. J.
|
|
<strong>The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment.</strong>
|
|
Am. J. Hum. Genet. 65: 59-67, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302439" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Kluijtmans1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., Boers, G. H. J., Stevens, E. M. B., Renier, W. O., Kraus, J. P., Trijbels, F. J. M., van den Heuvel, L. P. W. J., Blom, H. J.
|
|
<strong>Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient.</strong>
|
|
J. Clin. Invest. 98: 285-289, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI118791" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Kluijtmans1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., van den Heuvel, L. P. W. J., Boers, G. H. J., Frosst, P., Stevens, E. M. B., van Oost, B. A., den Heijer, M., Trijbels, F. J. M., Rozen, R., Blom, H. J.
|
|
<strong>Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease.</strong>
|
|
Am. J. Hum. Genet. 58: 35-41, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Kozich1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kozich, V., de Franchis, R., Kraus, J. P.
|
|
<strong>Molecular defect in a patient with pyridoxine-responsive homocystinuria.</strong>
|
|
Hum. Molec. Genet. 2: 815-816, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8353501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8353501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8353501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/2.6.815" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Kozich1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kozich, V., Kraus, J. P.
|
|
<strong>Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency.</strong>
|
|
Hum. Mutat. 1: 113-123, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380010206" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Kraus1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Janosik, M., Kozich, V., Mandell, R., Shih, V., Sperandeo, M. P., Sebastio, G., de Franchis, R., Andria, G., Kluijtmans, L. A. J., Blom, H., Boers, G. H. J., Gordon, R. B., Kamoun, P., Tsai, M. Y., Kruger, W. D., Koch, H. G., Ohura, T., Gaustadnes, M.
|
|
<strong>Cystathionine beta-synthase mutations in homocystinuria.</strong>
|
|
Hum. Mutat. 13: 362-375, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10338090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10338090</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10338090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<362::AID-HUMU4>3.0.CO;2-K" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Kraus1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Le, K., Swaroop, M., Ohura, T., Tahara, T., Rosenberg, L. E., Roper, M. D., Kozich, V.
|
|
<strong>Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells.</strong>
|
|
Hum. Molec. Genet. 2: 1633-1638, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7903580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7903580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7903580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/2.10.1633" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Kraus1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Oliveriusova, J., Sokolova, J., Kraus, E., Vlcek, C., de Franchis, R., Maclean, K. N., Bao, L., Bukovska, G., Patterson, D., Paces, V., Ansorge, W., Kozich, V.
|
|
<strong>The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.</strong>
|
|
Genomics 52: 312-324, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790750" 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.1998.5437" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Kraus1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kraus, J. P.
|
|
<strong>Molecular basis of phenotype expression in homocystinuria.</strong>
|
|
J. Inherit. Metab. Dis. 17: 383-390, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7967489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7967489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7967489" 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/BF00711354" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Kraus1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kraus, J., Packman, S., Fowler, B., Rosenberg, L. E.
|
|
<strong>Purification and properties of cystathionine beta-synthase from human liver: evidence for identical subunits.</strong>
|
|
J. Biol. Chem. 253: 6523-6528, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/681363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">681363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=681363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Kruger1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Cox, D. R.
|
|
<strong>A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 6614-6618, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8022826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8022826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8022826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.91.14.6614" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Kruger1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Cox, D. R.
|
|
<strong>A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.</strong>
|
|
Hum. Molec. Genet. 4: 1155-1161, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528202" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.7.1155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Kruger2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Wang, L., Jhee, K. H., Singh, R. H., Elsas, L. J., II.
|
|
<strong>Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.</strong>
|
|
Hum. Mutat. 22: 434-441, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14635102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14635102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14635102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.10290" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Kruger2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kruger, W. D.
|
|
<strong>Cystathionine beta-synthase deficiency: of mice and men.</strong>
|
|
Molec. Genet. Metab. 121: 199-205, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28583326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28583326</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28583326[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=28583326" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2017.05.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Lee2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, S.-J., Lee, D. H., Yoo, H.-W., Koo, S. K., Park, E.-S., Park, J.-W., Lim, H. G., Jung, S.-C.
|
|
<strong>Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria.</strong>
|
|
J. Hum. Genet. 50: 648-654, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16205833" 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/s10038-005-0312-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Maclean2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maclean, K. N., Gaustadnes, M., Oliveriusova, J., Janosik, M., Kraus, E., Kozich, V., Kery, V., Skovby, F., Rudiger, N., Ingerslev, J., Stabler, S. P., Allen, R. H., Kraus, J. P.
|
|
<strong>High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations.</strong>
|
|
Hum. Mutat. 19: 641-655, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12007221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12007221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12007221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.10089" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Munke1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Munke, M., Kraus, J. P., Ohura, T., Francke, U.
|
|
<strong>The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17.</strong>
|
|
Am. J. Hum. Genet. 42: 550-559, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2894761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2894761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2894761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Munke1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Munke, M., Kraus, J., Watkins, P., Tanzi, R., Gusella, J., Millington Ward, A., Watson, M., Francke, U.
|
|
<strong>Homocystinuria gene on human chromosome 21 mapped with cloned cystathionine beta-synthase probe and in situ hybridization of other chromosome 21 probes. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 40: 706-707, 1985.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Namekata2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Namekata, K., Enokido, Y., Ishii, I., Nagai, Y., Harada, T., Kimura, H.
|
|
<strong>Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia.</strong>
|
|
J. Biol. Chem. 279: 52961-52969, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15466479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15466479</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15466479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M406820200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Pogribna2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pogribna, M., Melnyk, S., Pogribny, I., Chango, A., Yi, P., James, S. J.
|
|
<strong>Homocysteine metabolism in children with Down syndrome: in vitro modulation.</strong>
|
|
Am. J. Hum. Genet. 69: 88-95, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11391481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11391481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11391481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/321262" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Robert2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robert, K., Chasse, J.-F., Santiard-Baron, D., Vayssettes, C., Chabli, A., Aupetit, J., Maeda, N., Kamoun, P., London, J., Janel, N.
|
|
<strong>Altered gene expression in liver from a murine model of hyperhomocysteinemia.</strong>
|
|
J. Biol. Chem. 278: 31504-31511, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12799373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12799373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12799373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M213036200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Robert2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robert, K., Vialard, F., Thiery, E., Toyama, K., Sinet, P.-M., Janel, N., London, J.
|
|
<strong>Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain.</strong>
|
|
J. Histochem. Cytochem. 51: 363-371, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1177/002215540305100311" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Scott2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scott, J. W., Hawley, S. A., Green, K. A., Anis, M., Stewart, G., Scullion, G. A., Norman, D. G., Hardie, D. G.
|
|
<strong>CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.</strong>
|
|
J. Clin. Invest. 113: 274-284, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722619</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722619[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=14722619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI19874" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Sebastio1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sebastio, G., Sperandeo, M. P., Panico, M., de Franchis, R., Kraus, J. P., Andria, G.
|
|
<strong>The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.</strong>
|
|
Am. J. Hum. Genet. 56: 1324-1333, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762555</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Sebastio1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sebastio, G.
|
|
<strong>Personal Communication.</strong>
|
|
Padua, Italy 3/20/1997.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Shan2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shan, X., Dunbrack, R. L., Jr., Christopher, S. A., Kruger, W. D.
|
|
<strong>Mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient-derived mutations in cis.</strong>
|
|
Hum. Molec. Genet. 10: 635-643, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11230183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.6.635" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Shan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shan, X., Kruger, W. D.
|
|
<strong>Correction of disease-causing CBS mutations in yeast.</strong>
|
|
Nature Genet. 19: 91-93, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0598-91" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Shih1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V.
|
|
<strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong>
|
|
Am. J. Hum. Genet. 57: 34-39, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7611293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Skovby2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skovby, F., Gaustadnes, M., Mudd, S. H.
|
|
<strong>A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency.</strong>
|
|
Molec. Genet. Metab. 99: 1-3, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19819175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19819175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19819175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2009.09.009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Skovby1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skovby, F., Krassikoff, N., Francke, U.
|
|
<strong>Assignment of the gene for cystathionine beta-synthase (CBS) to human chromosome 21 in somatic cell hybrids. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 585 only, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Skovby1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skovby, F., Krassikoff, N., Francke, U.
|
|
<strong>Assignment of the gene for cystathionine beta-synthase to human chromosome 21 in somatic cell hybrids.</strong>
|
|
Hum. Genet. 65: 291-294, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6583157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6583157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6583157" 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/BF00286520" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Skovby1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skovby, F., Kraus, J. P., Rosenberg, L. E.
|
|
<strong>Homocystinuria: biogenesis of cystathionine beta-synthase subunits in cultured fibroblasts and in an in vitro translation system programmed with fibroblast messenger RNA.</strong>
|
|
Am. J. Hum. Genet. 36: 452-459, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6711564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6711564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6711564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Sperandeo1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sperandeo, M. P., de Franchis, R., Andria, G., Sebastio, G.
|
|
<strong>A 68-bp insertion found in a homocystinuric patient is a common variant and is skipped by alternative splicing of the cystathionine beta-synthase mRNA. (Letter)</strong>
|
|
Am. J. Hum. Genet. 59: 1391-1393, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Sperandeo1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sperandeo, M. P., Panico, M., Pepe, A., Candito, M., de Franchis, R., Kraus, J. P., Andria, G., Sebastio, G.
|
|
<strong>Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11.</strong>
|
|
J. Inherit. Metab. Dis. 18: 211-214, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7564249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7564249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7564249" 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/BF00711769" target="_blank">Full Text</a>]
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<a id="56" class="mim-anchor"></a>
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<a id="Stubbs1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stubbs, L., Kraus, J., Lehrach, H.
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<strong>The alpha-A-crystallin and cystathionine beta-synthase genes are physically very closely linked in proximal mouse chromosome 17.</strong>
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Genomics 7: 284-288, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2347594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2347594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2347594" 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/10.1016/0888-7543(90)90553-7" target="_blank">Full Text</a>]
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<li>
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<a id="57" class="mim-anchor"></a>
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<a id="Tsai1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q.
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<strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong>
|
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Am. J. Hum. Genet. 59: 1262-1267, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="58" class="mim-anchor"></a>
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<a id="Urreizti2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urreizti, R., Asteggiano, C., Bermudez, M., Cordoba, A., Szlago, M., Grosso, C., de Kremer, R. D., Vilarinho, L., D'Almeida, V., Martinez-Pardo, M., Pena-Quintana, L., Dalmau, J., Bernal, J., Briceno, I., Couce, M. L., Rodes, M., Vilaseca, M. A., Balcells, S., Grinberg, D.
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<strong>The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.</strong>
|
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J. Hum. Genet. 51: 305-313, 2006. Note: Erratum: J. Hum. Genet. 52: 388-389, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16479318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16479318</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16479318" 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/s10038-006-0362-0" target="_blank">Full Text</a>]
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<li>
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<a id="59" class="mim-anchor"></a>
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<a id="Wang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, L., Chen, X., Tang, B., Hua, X., Klein-Szanto, A., Kruger, W. D.
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<strong>Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model.</strong>
|
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Hum. Molec. Genet. 14: 2201-2208, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15972722[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=15972722" 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/ddi224" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="60" class="mim-anchor"></a>
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<a id="Watanabe1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watanabe, M., Osada, J., Aratani, Y., Kluckman, K., Reddick, R., Malinow, M. R., Maeda, N.
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<strong>Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.</strong>
|
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Proc. Nat. Acad. Sci. 92: 1585-1589, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7878023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7878023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7878023" 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/10.1073/pnas.92.5.1585" target="_blank">Full Text</a>]
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</p>
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</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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Bao Lige - updated : 09/09/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="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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Carol A. Bocchini - updated : 07/18/2017
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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="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 : 4/26/2010
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</span>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 01/07/2025
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</span>
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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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mgross : 09/09/2022<br>carol : 07/19/2017<br>carol : 07/18/2017<br>carol : 10/21/2016<br>alopez : 04/29/2015<br>mcolton : 4/21/2015<br>carol : 9/29/2014<br>carol : 7/30/2010<br>carol : 5/5/2010<br>carol : 5/4/2010<br>carol : 5/4/2010<br>ckniffin : 5/3/2010<br>ckniffin : 4/28/2010
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<h3>
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<span class="mim-font">
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<strong>*</strong> 613381
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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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CYSTATHIONINE BETA-SYNTHASE; CBS
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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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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CBS</em></strong>
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</span>
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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: 21q22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 21:43,053,191-43,076,873 </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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<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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</tr>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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21q22.3
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<td>
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<span class="mim-font">
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Homocystinuria, B6-responsive and nonresponsive types
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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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236200
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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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<td>
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<span class="mim-font">
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Thrombosis, hyperhomocysteinemic
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</td>
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<td>
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<span class="mim-font">
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236200
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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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<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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<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>The CBS gene encodes cystathionine beta-synthase (EC 4.2.1.22), which catalyzes the first irreversible step of transsulfuration. The enzyme conjugates homocysteine and serine to form cystathionine, which is subsequently converted into cysteine and alpha-ketobutyrate. Homocysteine can also undergo remethylation to form methionine. The CBS enzyme is a homotetramer of 63-kD subunits and requires pyridoxal phosphate and heme for activity. It can also be stimulated by the addition of S-adenosylmethionine (AdoMet) (Kraus et al., 1993; Shan et al., 2001). </p>
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<br />
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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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<span class="mim-text-font">
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<p>Kraus et al. (1993) cloned the human CBS gene from a human liver cDNA library. The deduced 551-residue protein showed about 90% identity with the rat protein. Northern blot analysis identified a major 2.7-kb mRNA transcript. </p><p>Chasse et al. (1995) isolated clones corresponding to the CBS gene from a human liver cDNA library. The gene is expressed as a 2.5-kb mRNA species mostly in liver and pancreas, with faint expression in brain, heart, kidney and lung. In addition, a 3.7-kb transcript was found in pancreas and liver. </p><p>Using in situ hybridization and Northern blot analysis, Robert et al. (2003) found expression of the Cbs gene in early mouse development in the liver and in the skeletal, cardiac, and nervous systems. Expression declined in the nervous system in the late embryonic stages, whereas it increased in the brain after birth, peaking during cerebellar development. In the adult brain, expression was strongest in the Purkinje cell layer and in the hippocampus. Immunohistochemical analyses showed that the Cbs protein was localized in most areas of the brain, but predominantly in the cell bodies and neuronal processes of Purkinje cells and Ammon's horn neurons. </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>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>Chasse et al. (1997) reported that the human CBS gene spans over 30 kb and contains 19 exons. There are 3 different 5-prime untranslated regions, including 3 different exons 1: exon 1a, 1b, and 1c. Exons 1a and 1b are 390 bp apart and are linked to exon 2 in cDNAs reported by the authors. Exon 1c, which is linked to exon 5 in another cDNA, is 7 kb from exon 1b. All splice sites conform to the GT/AG rule, including those from exon 1a or 1b to exon 2 and from exon 1c to exon 5. Their results suggested that the mRNAs containing the different exons 1 are under the control of different promoters. </p><p>By genomic sequence analysis, Kraus et al. (1998) determined that the CBS gene contains 23 exons, ranging in size from 42 to 299 bp. The 5-prime UTR is formed by 1 of 5 alternatively used exons and 1 invariably present exon. The 3-prime UTR is encoded by exons 16 and 17. Kraus et al. (1998) also described 2 alternatively used GC-rich promoter regions. The authors noted that the CBS locus contains an unusually high number of Alu repeats and suggested that these may predispose the gene to deleterious rearrangements. </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>Studying somatic cell hybrids between human fibroblasts with normal cystathionine beta-synthase activity and hamster cells without this enzyme activity, Skovby et al. (1984, 1984) found that enzyme activity cosegregated with chromosome 21. No enzyme activity was found in homocystinuric fibroblasts. </p><p>By in situ hybridization, Munke et al. (1985) assigned the CBS locus to chromosome 21q22. Using a rat cDNA probe for in situ hybridization to structurally rearranged chromosomes 21, Munke et al. (1988) assigned CBS to the subtelomeric region of band 21q22.3. </p><p>Chadefaux et al. (1985) demonstrated a dosage effect for CBS enzymatic activity in fibroblasts from patients trisomic for chromosome 21, and in cases of deletion and partial trisomy found levels of activity consistent with location of the CBS locus between 21q22.1 and 21q21. </p><p>Munke et al. (1988) mapped the mouse gene to the proximal half of chromosome 17 by Southern analysis of hamster-mouse somatic cell hybrid DNA. </p><p>Stubbs et al. (1990) demonstrated that the murine equivalents of the CBS and CRYA1 (123580) genes are very closely situated on mouse chromosome 17 in a segment not larger than 130 kb. Most of the genes concentrated in band 21q22, which may be relevant to the phenotype of Down syndrome, are located on mouse chromosome 16 or mouse chromosome 10. The close physical linkage of the mouse equivalents of CBS and CRYA1, combined with data that localize closely flanking mouse markers to human chromosome 6, suggest that the human 21q22/mouse chromosome 17 conserved segment is of limited physical size and contains a small number of Down syndrome-related genes. </p><p>Avramopoulos et al. (1993) used single-strand conformation polymorphism (SSCP) to detect DNA polymorphisms in the 3-prime untranslated region of the CBS gene. Using one of these for linkage studies in CEPH families, they placed the CBS gene on human chromosome 21. </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>Gene Function</strong>
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<p>The human CBS protein can substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae (Kruger and Cox, 1994). </p><p>Heme may be necessary for binding of pyridoxal 5-prime phosphate to CBS and for correct CBS folding (Kery et al., 1999). </p><p>The catalytic domain of the CBS protein is located in the N-terminal 409 amino acids, and a regulatory domain is located in the C-terminal 142 amino acids. Using the Kruger-Cox yeast system for studying human CBS gene function, Shan and Kruger (1998) reported that a mutation that deletes the C-terminal 145 amino acids of CBS could restore activity of several CBS mutant alleles found in homocystinurics. This C-terminal domain must thus act to inhibit enzymatic activity. In addition, the C-terminal domain is in turn regulated by S-adenosylmethionine (AdoMet), a positive effector of CBS. Shan and Kruger (1998) suggested that most mutations in patients with homocystinuria do not cause dysfunction of the catalytic domain, but rather interfere with the activation of the enzyme. These findings suggested a new drug target to treat homocystinuria and homocysteine-related vascular disease. Shan et al. (2001) used a yeast genetic screen to identify missense mutations in the C-terminal region of CBS that could suppress the most common patient mutation, I278T (613381.0004). Seven suppressor mutations were identified, 4 of which mapped to the C-terminal regulatory domain. When combined in cis with another pathogenic mutation, val168-to-met (V168M; 613381.0011), 6 of 7 of the suppressor mutations rescued the yeast phenotype. Enzyme activity analyses indicated that the suppressors restored activity from less than 2% to 17 to 64% of the wildtype levels. Analysis of the suppressor mutations in the absence of the pathogenic mutation showed that 6 of the 7 suppressor alleles had lost enzymatic responsiveness to S-adenosylmethionine. Using homology modeling, the suppressor mutations appeared to map on one face of the regulatory domain. The authors concluded that subtle changes to the C terminus of CBS may restore activity to mutant proteins, which could provide a rationale for screening for compounds that could activate mutant CBS alleles. </p><p>The CBS gene on chromosome 21 is overexpressed in patients with trisomy 21 (190685). Pogribna et al. (2001) evaluated homocysteine metabolism in Down syndrome and sought to determine whether the supplementation of trisomy 21 lymphoblasts in vitro with selected nutrients would shift the genetically induced metabolic imbalance. They found that the increased activity of CBS in Down syndrome significantly alters homocysteine metabolism so that the folate-dependent resynthesis of methionine is compromised. The decreased availability of homocysteine promotes the well-established 'folate trap,' creating a functional folate deficiency that may contribute to the metabolic pathology of this complex genetic disorder. </p><p>CBS domains were originally identified as sequence motifs of approximately 60 amino acids that occur in cystathionine beta-synthase, and several other proteins, in all organisms from archaea to humans (Bateman, 1997). Their functional importance was emphasized by findings that point mutations within them cause several hereditary diseases in humans, including homocystinuria. Scott et al. (2004) showed that tandem pairs of CBS domains from AMP-activated protein kinase, IMP dehydrogenase-2 (IMPDH2; 146691), the chloride channel CLC2 (600570), and cystathionine beta-synthase bind AMP, ATP, or S-adenosylmethionine, whereas mutations that cause hereditary diseases impair this binding. This showed that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a class of binding domain for adenosine derivatives. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<p>Kraus (1994) tabulated 14 mutations in the CBS gene that he and his colleagues had demonstrated in homocystinuria (236200). The G307S mutation (613381.0001) is the most common cause of homocystinuria in patients of Celtic origin. Kraus (1994) indicated that even though patients have no measurable CBS activity in their fibroblasts and despite the fact that CBS subunits are undetectable in fibroblast extracts of some of these individuals, many of them are pyridoxine-responsive. Examples were cited in which the identical genotype resulted in a different phenotype within the family. In general, G307S is a pyridoxine-nonresponsive mutation, whereas I278T (613381.0004) is a pyridoxine-responsive mutation (Hu et al., 1993). </p><p>Sebastio et al. (1995) identified a 68-bp insertion in exon 8 of the CBS gene (613381.0017) in a patient with homocystinuria and predicted that it would introduce a premature termination codon and result in a nonfunctional CBS enzyme. However, Tsai et al. (1996) found that this mutation is highly prevalent. In a case-control study involving patients with premature coronary artery disease, they identified the mutation in heterozygosity in 11.7% of controls and in slightly higher prevalence in the patients, although the difference did not reach statistical significance. In all cases, the insertion was present in cis with the 833T-C (I278T) mutation. Tsai et al. (1996) suggested that the insertion created an alternate splicing site that eliminated not only the inserted intronic sequences, but also the 833T-C mutation associated with this insertion. The net result was the generation of both quantitatively and qualitatively normal mRNA and CBS enzyme. </p><p>Kraus et al. (1999) stated that 92 different disease-associated mutations of the CBS gene had been identified in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations were missense, and the vast majority of these were private mutations occurring in only 1 or a very small number of families. The 2 most frequently encountered mutations were the pyridoxine-responsive I278T (613381.0004) and the pyridoxine-nonresponsive G307S (613381.0001). Mutations due to deaminations of methylcytosines represented 53% of all point substitutions in the coding region of the CBS gene. </p><p>Janosik et al. (2001) reported observations suggesting that inability to bind heme may prevent correct folding and subsequent tetramer formation of mutant and, to a lesser extent, normal CBS subunits. They postulated that, as with other genetic defects (Bross et al., 1999), mutant CBS misfolding and aggregation may be the primary defect in a significant proportion of patients with homocystinuria. </p><p>In 6 patients from 5 Korean families with homocystinuria, Lee et al. (2005) identified 8 different mutations in the CBS gene, including 4 novel mutations. In vitro functional expression studies showed that the mutant enzymes had significantly decreased activities. </p>
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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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</h4>
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<p>Watanabe et al. (1995) generated mice that were moderately and severely homocysteinemic, using homologous recombination in mouse embryonic stem cells to inactivate the Cbs gene. Homozygous mutants completely lacking cystathionine beta-synthase were born at the expected frequency from matings of heterozygotes, but they suffered from severe growth retardation and most of them died within 5 weeks after birth. Histologic examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets (resembling the finding in some severe homocystinuric patients). Plasma homocysteine levels of the homozygotes were approximately 40 times normal. Heterozygous mutants had approximately 50% reduction in CBS mRNA and enzyme activity in the liver and had twice normal plasma homocysteine levels. Watanabe et al. (1995) concluded that homozygotes are a useful model for the clinical disorder homocystinuria and the heterozygotes should be useful for studying the role of elevated levels of homocysteine in the causation of cardiovascular disease. They noted that most of the homozygous mutant mice had eyes with delayed and narrow eye openings but without obvious histologic abnormalities. Seemingly, the homozygotes did not survive long enough to develop osteoporosis and vascular occlusions. </p><p>Robert et al. (2003) found that Cbs-null mice fed a standard diet died before 1 month of age. Chow enriched with choline chloride allowed longer survival. Homocysteine was significantly increased in plasma and liver of Cbs-null mice compared to controls. Gene expression measured by Northern blot analysis showed altered expression of genes encoding ribosomal protein S3a (RPS3A; 180478) and MTAP (156540), suggesting changes in cellular growth and proliferation. In addition, many up- or down-regulated genes indicated perturbations of the redox potential, including cytochromes P450 (see, e.g., 107910), heme oxygenase 1 (HMOX1; 141250), and PON1 (168820), suggesting increased oxidative stress in these animals. </p><p>Namekata et al. (2004) found that Cbs-null mice had abnormal lipid metabolism, with markedly increased triglyceride and nonesterified fatty acid levels in liver and serum. Thiolase activity was significantly impaired and hepatic apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and very low density lipoprotein levels were increased. Other findings included decreased activity of LCAT (606967) and altered serum cholesterol/triglyceride distribution in lipoprotein fractions. These findings suggested impaired beta-oxidation of fatty acids, and indicated that hepatic steatosis in Cbs-null mice is caused by or associated with abnormal lipid metabolism. </p><p>Wang et al. (2005) engineered mice that expressed the common human mutant I278T and I278T/T424N Cbs proteins. These transgene-containing mice were then bred to Cbs +/- mice to generate Cbs -/- mice that expressed only the I278T or I278T/T424N human transgenes. Both the I278T and the I278T/T424N transgenes were able to entirely rescue the neonatal mortality phenotype of Cbs -/- mice (see Watanabe et al., 1995) despite these mice having a mean homocysteine level of 250 micromols. The transgenic Cbs -/- animals exhibited facial alopecia, had moderate liver steatosis, and were slightly smaller than heterozygous littermates. In contrast to human CBS deficiency, these mice did not exhibit hypermethioninemia. The mutant proteins were stable in several tissues, although liver extracts had only 2 to 3% of the Cbs enzyme activity found in wildtype mice. The I278T/T424N enzyme had exactly the same activity as the I278T enzyme, indicating that T424N was unable to suppress I278T in mice. Wang et al. (2005) concluded that elevated homocysteine levels per se were not responsible for the neonatal lethality observed in Cbs -/- animals and suggested that CBS protein may have other functions in addition to its role in homocysteine catabolism. </p><p>Kruger (2017) reviewed mouse models of CBS deficiency that express either low levels of wildtype or mutant human CBS proteins. The models mimic the metabolic sequelae of the disease and present similar skeletal defects and body composition differences. They appear to be a good system for studying the effects of dietary alterations on these phenotypes. For example, mice on a low methionine diet, like treated human patients, show a significant reduction in homocysteine-related phenotypes. Vascular differences in these mice are not a major source of morbidity as they are in the human disease. Plaque rupture, for example, the main source of thrombotic events in humans, is almost never seen in these mice. A dislocated lens phenotype is not observed in these mouse models, and the pyridoxine responsiveness in humans is not replicated in these mice. </p><p>Behera et al. (2018) found that Cbs +/- mice developed hyperhomocysteinemia (HHCY). Analysis of bone marrow mesenchymal stem cells (BMMSCs) from Cbs +/- mice showed that Cbs was essential for production of H2S, a gasotransmitter molecule that regulates bone formation. Administration of H2S ameliorated HHCY-induced redox homeostasis and prevented bone loss in Cbs +/- mice. Cbs deficiency-induced HHCY caused alternation of chromatin landscapes and inflammation by attenuating histone acetylation activity. Specifically, HHCY induced Nfkb (see 164014) acetylation to promote histone acetylation-dependent proinflammatory signaling, which was ameliorated by administration of H2S in Cbs +/- mice. H2S induced osteogenic gene expression by suppressing histone acetylation-dependent Nfkb signaling activation and inflammation. In vitro analysis with Cbs +/- mouse BMMSCs revealed that HHCY induced secretion of inflammatory cytokines to upregulate osteoclastogenesis, but it was reversed by treatment with H2S. H2S promoted osteogenesis and was required for osteoblast biologic activity, including differentiation, maturation, and mineralization. In vivo analysis in Cbs +/- mice indicated that H2S was required for normal bone homeostasis and potentially mitigated Cbs deficiency-induced osteoporosis. As a result, H2S deficiency in Cbs +/- mice induced generation of reactive oxygen species (ROS) in BMMSCs and potentiated osteoporotic bone loss. Further analysis demonstrated that osteogenic marker Runx2 (600211) was sulfhydrated after H2S treatment and mediated osteogenesis. </p>
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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>
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<strong>17 Selected Examples):</strong>
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</span>
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</h4>
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<p />
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<h4>
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<span class="mim-font">
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<strong>.0001 HOMOCYSTINURIA, PYRIDOXINE-NONRESPONSIVE</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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HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, INCLUDED
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</span>
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<div>
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<span class="mim-text-font">
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CBS, GLY307SER
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<br />
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SNP: rs121964962,
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gnomAD: rs121964962,
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ClinVar: RCV000000137, RCV000000138, RCV000078112, RCV000173641, RCV000366433, RCV002313701, RCV003914786
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</span>
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</div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Homocystinuria</em></strong></p><p>
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In 2 unrelated patients with homocystinuria (236200), Gu et al. (1991) found a G-to-A transition in the CBS gene, resulting in a gly307-to-ser (G307S) substitution. Functional expression studies in E. coli showed a peptide of normal mobility that lacked CBS activity.</p><p>Hu et al. (1993) found the G307S mutation in one allele of a patient of French/Scottish ancestry and in both alleles of a patient of Irish ancestry. Both parents of the second patient were heterozygotes for G307S. The mutant protein was apparently stable in expression studies in E. coli but lacked catalytic activity. Sequencing of exon 8 revealed the G307S mutation in 5 additional families. All had pyridoxine-nonresponsive homocystinuria. </p><p>Hu et al. (1993) observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic backgrounds. All 9 were from patients with Celtic (Irish/English/Scottish/French) ancestry in either one or both parents. Indeed, the G307S mutation was detected in 9 of 18 Celtic alleles in their series. A second mutation found in exon 8 (I278T; 613381.0004) was associated with pyridoxine responsiveness. </p><p>Gallagher et al. (1995) analyzed 17 Irish unrelated persons with homocystinuria for the G307S mutation. Homozygosity for the mutation was found in 8 of the 17. A further 8 patients were compound heterozygotes, with the G307S mutation present on 1 allele. Of the 34 alleles, 24 (71%) were G307S. Screening of newborns for homocystinuria has been routine in Ireland since 1971. Newly diagnosed infants are also assessed for responsiveness to pyridoxine; all patients analyzed by Gallagher et al. (1995) were nonresponsive. </p><p>Kim et al. (1997) found a different distribution of CBS alleles in Norwegian cystinurics. The G307S mutation, which was found in 71% of mutant alleles in Ireland, accounted for only 20% in the Norwegian group and in Italian patients was not observed at all (Sperandeo et al., 1995). </p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
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In a patient with early-onset stroke and hyperhomocysteinemia without other manifestations of classic homocystinuria (see 236200), Kelly et al. (2003) identified a heterozygous G307S mutation. The patient was an 18-year-old Irish man with mitral valve prolapse who had an ischemic stroke. A second CBS mutation was not identified. </p>
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, PRO145LEU
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<br />
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SNP: rs121964963,
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gnomAD: rs121964963,
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ClinVar: RCV000000139, RCV000625555, RCV001250193, RCV002227955
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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 an adult female patient of Irish and German ancestry with relatively mild and late-onset signs of homocystinuria (236200) responsive to pyridoxine, Kozich et al. (1993) found compound heterozygosity for 2 different mutations of the CBS gene: a 434C-T transition resulting in a pro145-to-leu (P145L) substitution, and a 341C-T transition resulting in an ala114-to-val (A114V; 613381.0003) substitution. </p>
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</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>
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<span class="mim-font">
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<strong>.0003 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, ALA114VAL
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<br />
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SNP: rs121964964,
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gnomAD: rs121964964,
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ClinVar: RCV000000140, RCV000200823, RCV000490533, RCV000590659, RCV002227956, RCV002453244, RCV003952330
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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>For discussion of the ala114-to-val (A114V) mutation in the CBS gene that was found in compound heterozygous state in a patient with homocystinuria (236200) by Kozich et al. (1993), see 613881.0002. </p>
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</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>
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<span class="mim-font">
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<strong>.0004 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, INCLUDED
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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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CBS, ILE278THR
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<br />
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SNP: rs5742905,
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gnomAD: rs5742905,
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ClinVar: RCV000000141, RCV000000142, RCV000078111, RCV000173640, RCV000781197, RCV001252178, RCV002276525, RCV002310621, RCV003128384, RCV004584135
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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 />
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<p><strong><em>Homocystinuria</em></strong></p><p>
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On both alleles of a pyridoxine-responsive Polish patient with homocystinuria, Hu et al. (1993) identified an 833T-C transition in exon 8 of the CBS gene, resulting in an ile278-to-thr (I278T) substitution. They also identified this mutation on 1 allele of a pyridoxine-nonresponsive Polish patient. </p><p>In a mildly affected pyridoxine-responsive patient of Ashkenazi Jewish origin, Kozich and Kraus (1992) identified compound heterozygosity for a maternal I278T mutation and a paternal IVS11-2A-C mutation (613381.0012). </p><p>By PCR amplification and sequencing of exon 8 from genomic DNA, Shih et al. (1995) detected the I278T mutation in 7 of 11 patients with in vivo pyridoxine-responsiveness and in none of 27 pyridoxine-nonresponsive patients; 2 pyridoxine-responsive patients were homozygous and 5 were heterozygous for I278T. They further observed the I278T mutation in 9 (41%) of 22 independent alleles in pyridoxine-responsive patients of various ethnic backgrounds. In 2 of the compound heterozygotes, they identified novel mutations (G139R, 613381.0005 and E144K, 613381.0006) on the other allele. The 2 patients who were homozygous for I278T had only ectopia lentis and mild bone demineralization. Shih et al. (1995) concluded that compound heterozygous patients who have one copy of the I278T mutation are likely to retain some degree of pyridoxine responsiveness. </p><p>Although the 833T-C mutation is found in 50% of the CBS alleles in Dutch homozygous CBS-deficient patients, Kluijtmans et al. (1996) found it in none of 60 patients with premature cardiovascular disease. This led them to conclude that heterozygosity for CBS deficiency is not involved in premature cardiovascular disease. </p><p>In a study of 21 unrelated Dutch pedigrees, Kluijtmans et al. (1999) found that of 10 different mutations detected in the CBS gene, I278T was predominant, being present in 23 (55%) of 42 independent alleles. Homozygotes for this mutation tended to have higher homocysteine levels than those in patients with other genotypes, but similar clinical manifestations. I278T homozygotes responded more efficiently to homocysteine-lowering treatment. After 378 patient-years of treatment, only 2 vascular events were recorded; without treatment at least 30 would have been expected. </p><p>The I278T mutation is the most frequent mutation in homocystinuria in Italy, where most cases are B6-responsive and the disorder has a total frequency of approximately 1 in 55,000 as compared with a frequency of 1 in 58,000 in the United States and 1 in 889,000 in Japan (Sebastio, 1997).</p><p>Gaustadnes et al. (1999) stated that the I278T mutation is geographically widespread. They determined the frequency of this mutation among Danish newborns by screening 500 consecutive Guthrie cards (specimens of infants' blood collected on filter paper). A surprisingly high prevalence of the 833T-C mutation was detected among newborns, suggesting that the incidence of homocystinuria due to homozygosity for this mutation may be at least 1 per 20,500 live births in Denmark. </p><p>In a study of 11 families in the state of Georgia (USA), Kruger et al. (2003) found that the I278T and T353M (613381.0015) mutations accounted for 45% of the mutant alleles. The T353M mutation, found exclusively in 4 African American patients, was associated with a B6-nonresponsive phenotype and detection by neonatal screening for hypermethioninemia. The I278T mutation was found exclusively in Caucasian patients and was associated with a B6-responsive phenotype. </p><p>In a population-based study in Denmark, Skovby et al. (2010) concluded that the predominant portion of individuals who are homozygous for the I278T mutation may be clinically unaffected or may only be ascertained after the third decade due to a thromboembolic event. These individuals do not have most of the clinical features of complete CBS deficiency. </p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
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In a patient with early-onset stroke and hyperhomocysteinemia without other classic features of homocystinuria (see 236200), Kelly et al. (2003) identified a heterozygous I278T mutation. The patient was a 47-year-old white woman of northern European descent with a thrombus in the right internal carotid artery. Kelly et al. (2003) postulated that she might have another, unidentified CBS mutation. </p>
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</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>
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<span class="mim-font">
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<strong>.0005 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, GLY139ARG
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<br />
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SNP: rs121964965,
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gnomAD: rs121964965,
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ClinVar: RCV000000143, RCV002468954, RCV003764500
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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>For discussion of the gly139-to-arg (G139R) mutation in the CBS gene that was found in compound heterozygous state in patients with pyridoxine-responsive homocystinuria (236200) by Shih et al. (1995), see 613381.0004. </p>
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</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>
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<span class="mim-font">
|
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<strong>.0006 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, GLU144LYS
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<br />
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SNP: rs121964966,
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gnomAD: rs121964966,
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ClinVar: RCV000000144, RCV000169074, RCV000723427, RCV001251284, RCV002227957, RCV003415595
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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>For discussion of the glu144-to-lys (E144K) mutation in the CBS gene that was found in compound heterozygous state in patients with pyridoxine-responsive homocystinuria (236200) by Shih et al. (1995), see 613381.0004. </p>
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</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>
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<span class="mim-font">
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<strong>.0007 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, LYS384GLU
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<br />
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SNP: rs121964967,
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ClinVar: RCV000000145, RCV003495103
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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 2 unrelated French vitamin B6-responsive homocystinuria (236200) patients with no Celtic origin, Aral et al. (1997) demonstrated novel mutations in the CBS gene. One patient had unilateral lens subluxation and deep vein thrombosis at age 6, and a Marfan-like appearance with thinning of long bones and digits, together with osteoporosis of the lower limbs. This patient was homozygous for a 1150A-G transition, resulting in a substitution lys384-to-glu (K384E). See also 613381.0008. </p>
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</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>
|
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<span class="mim-font">
|
|
<strong>.0008 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, LEU539SER
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<br />
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SNP: rs121964968,
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ClinVar: RCV000000146, RCV000675072, RCV002468955, RCV003597960
|
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|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with pyridoxine-responsive homocystinuria (236200), Aral et al. (1997) demonstrated homozygosity for a leu539-to-ser (L539S) mutation in the CBS gene. See also 613381.0007. </p>
|
|
</span>
|
|
</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>.0009 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</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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CBS, ARG266LYS
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<br />
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SNP: rs121964969,
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gnomAD: rs121964969,
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ClinVar: RCV000000147, RCV000469164, RCV001192721, RCV001546787, RCV002227958, RCV002313702
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Kim et al. (1997) found that 5 of 7 Norwegian patients classified as having pyridoxine-responsive homocystinuria (236200) had a 797G-A transition in the CBS gene, resulting in an arg266-to-lys (R266K) substitution. Kim et al. (1997) tested the effect of all the mutations identified on human CBS function utilizing a yeast system. Five of the 6 mutations had a distinguishable phenotype in yeast, indicating that they were, in fact, pathogenic. The 797G-A had no phenotype when the yeast were grown in high concentrations of pyridoxine, but a severe phenotype when grown in low concentrations, thus mirroring the behavior in humans. The yeast functional assay was suggested as a guide to therapy. </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>.0010 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, INCLUDED
|
|
</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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|
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CBS, ASP444ASN
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<br />
|
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|
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SNP: rs28934891,
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|
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|
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gnomAD: rs28934891,
|
|
|
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|
|
ClinVar: RCV000000148, RCV000000149, RCV000078108, RCV000174656, RCV000781196, RCV002381232, RCV004754226
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Homocystinuria</em></strong></p><p>
|
|
In a 20-year-old woman with pyridoxine-responsive homocystinuria (236200), Kluijtmans et al. (1996) identified a homozygous 1330G-A transition in the CBS gene, resulting in an asp444-to-asn (D444N) substitution in the regulatory domain of the protein. She was first admitted to the hospital at the age of 9 years because of psychomotor retardation, marfanoid features with excessive height, dolichostenomelia, arachnodactyly, and homocystinuria. She was treated with pyridoxine, folic acid, and betaine, with favorable results. Eleven years later she was in very good physical condition and her intellectual development had reached an average level. Ectopia lentis, osteoporosis, and vascular complications had not occurred. Both parents and an unaffected sister were heterozygous for the mutation. Despite the homozygous mutation, CBS activities in extracts of cultured fibroblasts of this patient were not in the homozygous but in the heterozygous range. In vitro functional expression studies showed no stimulation of CBS activity by S-adenosylmethionine, contrary to a 3-fold stimulation in control fibroblast extract. These data suggested that the D444N mutation interfered with S-adenosylmethionine regulation of CBS. Furthermore, it indicated the importance of S-adenosylmethionine regulation of the transsulfuration pathway in homocysteine homeostasis in humans. </p><p>CBS domains are defined as sequence motifs that occur in several different proteins in all kingdoms of life. Their functional importance is underlined by the finding that mutations in conserved residues within them cause a variety of human hereditary diseases, including homocystinuria. Scott et al. (2004) showed that tandem pairs of CBS domains from cystathionine beta-synthase, as well as the CBS domains from at least 3 other proteins that are the sites of mutations causing hereditary diseases, bind AMP, ATP, or S-adenosylmethionine, whereas mutations that cause hereditary diseases impair this binding. An interesting feature of the pathogenic mutations in CBS domains is that they tend to occur in equivalent positions. Thus, 3 mutations in the PRKAG2 gene that cause disease--R302Q (602743.0001), H383R, and R531G (602743.0006)--all align (plus or minus 1 residue) with the D444N mutation in the CBS gene. </p><p><strong><em>Hyperhomocysteinemia, Thrombotic, CBS-related</em></strong></p><p>
|
|
In a patient with early-onset stroke and hyperhomocysteinemia without other manifestations of homocystinuria (see 236200), Kelly et al. (2003) identified a heterozygous D444N mutation. The patient was a 39-year-old Venezuelan man who had a retinal artery occlusion due to an arterial dissection. An unaffected sister was also heterozygous for the mutation. The presence of a second mutation could not be excluded. </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>.0011 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, VAL168MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964970,
|
|
|
|
|
|
gnomAD: rs121964970,
|
|
|
|
|
|
ClinVar: RCV000000150, RCV000179250, RCV000458159, RCV002227959, RCV002265542, RCV002310622
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line from a patient with pyridoxine-responsive homocystinuria (236200), Kruger and Cox (1995) identified a 502G-A transition in the CBS gene, resulting in a val168-to-met (V168M) substitution in the catalytic domain. Shan et al. (2001) identified 7 mutations that could suppress the most common CBS patient mutation, I278T (613381.0004), 4 of which mapped to the C-terminal regulatory domain. The suppressors, in combination with the V168M mutation, also expressed a full-length protein. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 HOMOCYSTINURIA, PYRIDOXINE-RESPONSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, IVS11AS, A-C, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs375846341,
|
|
|
|
|
|
gnomAD: rs375846341,
|
|
|
|
|
|
ClinVar: RCV000000151, RCV000174658, RCV000198380, RCV000590542, RCV002227960, RCV002354142, RCV003944786
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mildly affected patient of Ashkenazi Jewish origin with pyridoxine-responsive homocystinuria (236200), Kozich and Kraus (1992) identified compound heterozygosity for a maternal I278T mutation (613381.0004) and a paternal A-to-C transversion in the intron 11 splice acceptor. The latter mutation led to an in-frame deletion of exon 12. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, PRO422LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28934892,
|
|
|
|
|
|
gnomAD: rs28934892,
|
|
|
|
|
|
ClinVar: RCV000000152, RCV000522394, RCV000675050, RCV002444412
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a group of unrelated patients that were screened for elevated homocysteine after an idiopathic thrombotic event (see 236200), Gaustadnes et al. (2000) found that 1 was compound heterozygous for 2 mutations in the CBS gene: a pro422-to-leu substitution in the C-terminal regulatory domain, and an asp444-to-asn mutation (613381.0010). The diagnosis of elevated homocysteine had been made after an episodic transient ischemic attack at the age of 22 years. The patient was found to be nonresponsive to therapy with either pyridoxine or betaine. The patient did not carry the 677C-T transition in the MTHFR gene (607093.0003). The usual manifestations of classic homocystinuria such as ectopia lentis, marfanoid skeletal features, and mental retardation were lacking. In vitro functional expression studies showed that the P422L mutant protein was catalytically active and even had higher activity than wildtype, but was impaired in regulation by AdoMet. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, SER466LEU
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121964971,
|
|
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|
|
|
gnomAD: rs121964971,
|
|
|
|
|
|
ClinVar: RCV000000153, RCV000675119, RCV002390082, RCV003226154
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 39-year-old woman with high homocysteine levels when screened after an episodic transient ischemic attack at the age of 36 years (see 236200) (Gaustadnes et al., 2000), Maclean et al. (2002) found compound heterozygosity for 2 mutations in the CBS gene: I278T (613381.0004) and a 139C-T transition, resulting in a ser466-to-leu (S466L) substitution in the C-terminal regulatory domain. The patient had no ectopia lentis, mental retardation, marfanoid skeletal features, or other characteristic features of classic homocystinuria (236200). In vitro functional expression studies showed that the S466L mutant protein was catalytically active and even had higher activity than wildtype, but was impaired in regulation by AdoMet. </p><p>Gupta et al. (2008) demonstrated that the S466L mutation in mice causes homocystinuria by affecting both the steady-state level of CBS and by reducing the efficiency of the enzyme. In the presence of zinc, the mean serum total homocysteine of transgenic S466L mice was 142(+/-55) microM compared to 16(+/-13) microM for wildtype. Transgenic mice also had significantly higher levels of total free homocysteine and S-adenosylhomocysteine in liver and kidney. Only 48% of S466L mice had detectable CBS protein in the liver, whereas all the wildtype animals had detectable protein. However, CBS mRNA was significantly elevated in transgenic mice, suggesting that the reduction in mutant protein resulted from posttranscriptional mechanisms. The mutant enzyme formed tetramers and was active, but lacked inducibility by S-adenosylmethionine. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HOMOCYSTINURIA, PYRIDOXINE-NONRESPONSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, THR353MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964972,
|
|
|
|
|
|
gnomAD: rs121964972,
|
|
|
|
|
|
ClinVar: RCV000000154, RCV000078106, RCV000169466, RCV002227961, RCV002271361, RCV004018522
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the state of Georgia (USA), Kruger et al. (2003) studied 11 families with CBS deficiency (236200). A thr353-to-met (T353M) mutation, found exclusively in 4 African American patients, was associated with a B6-nonresponsive phenotype and with detection by newborn screening for hypermethioninemia. The I278T (613381.0004) and T353M mutations accounted for 45% of the mutant alleles in the affected members of the 11 families. The I278T mutation was found exclusively in Caucasian patients and was associated with a B6-responsive phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 HOMOCYSTINURIA, PYRIDOXINE-NONRESPONSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CBS, THR191MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964973,
|
|
|
|
|
|
gnomAD: rs121964973,
|
|
|
|
|
|
ClinVar: RCV000000155, RCV000195441, RCV000576767, RCV000589097, RCV002227962, RCV003914787, RCV004018523
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 35 patients from 30 pedigrees with homocystinuria (236200) from the Iberian peninsula and several South American countries, Urreizti et al. (2006) found a high frequency of a 572C-T transition in the CBS gene, resulting in a thr191-to-met (T191M) substitution. The patients were from Spain, Portugal, Colombia, and Argentina. Combined with previously reported studies, the prevalence of T191M among mutant CBS alleles in different countries was 0.75 in Colombia, 0.52 in Spain, 0.33 in Portugal, 0.25 in Venezuela, 0.20 in Argentina, and 0.14 in Brazil. Haplotype analysis suggested a double origin for this mutation. The phenotype was B6-nonresponsive. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 CBS POLYMORPHISM</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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CBS, 68-BP INS
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<br />
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ClinVar: RCV000222887, RCV000990351, RCV001573597, RCV002225098, RCV002229201, RCV004020589
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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>Sebastio et al. (1995) identified a 68-bp insertion in exon 8 of the CBS gene in a patient with homocystinuria and predicted that it would introduce a premature termination codon and result in a nonfunctional CBS enzyme. However, Tsai et al. (1996) found that this mutation is highly prevalent. In a case-control study involving patients with premature coronary artery disease, they identified the mutation in heterozygosity in 11.7% of controls and in slightly higher prevalence in the patients, although the difference did not reach statistical significance. In all cases, the insertion was present in cis with the 833T-C (I278T; 613381.0004) mutation. Tsai et al. (1996) suggested that the insertion created an alternate splicing site that eliminated not only the inserted intronic sequences, but also the 833T-C mutation associated with this insertion. The net result was the generation of both quantitatively and qualitatively normal mRNA and CBS enzyme. </p>
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<div class="mim-changed mim-change"><p>Sperandeo et al. (1996) identified the 68-bp insertion as a benign polymorphism in an Italian cohort. </p></div>
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<p>Kim et al. (1997) studied the mutations in 10 Norwegian CBS-deficient families and identified 18 of the 20 mutant alleles. In 9 of the 20 CBS alleles (45%), they found the 68-bp duplication allele. This frequency was much higher than the 6% reported by Tsai et al. (1996) in a study population from the upper midwest of the US. In unaffected Norwegian chromosomes, Kim et al. (1997) found the frequency of the duplication to be approximately 5.5% (2 in 36). </p>
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<p>Franco et al. (1998), who referred to the 68-bp insertion in the coding region of exon 8 of the CBS gene as 844ins68, investigated its prevalence in 405 persons belonging to 4 different ethnic groups. The insertion was found in heterozygous state in 14 of 104 whites (13.5%), was absent among Asians, and was found in only 1 of 220 Amerindian chromosomes analyzed, whereas a much higher prevalence was observed among blacks (37.7% of heterozygotes and 4% of mutant homozygotes). In all carriers of the insertion, the 833T-C CBS mutation cosegregated in cis with 844ins68. The finding of the double mutant among blacks and Caucasians suggested that it antedated the divergence between Africans and non-Africans, and provided evidence for a partly or completely neutralizing effect conferred by the 68-bp insertion, since it allows the skipping of the 833T-C mutation. </p>
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</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>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Goldstein et al. (1972); Kim and Rosenberg (1974); Kraus et al.
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(1978); Skovby et al. (1984)
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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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aral, B., Coude, M., London, J., Aupetit, J., Chasse, J.-F., Zabot, M.-T., Chadefaux-Vekemans, B., Kamoun, P.
|
|
<strong>Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients.</strong>
|
|
Hum. Mutat. 9: 81-82, 1997.
|
|
|
|
|
|
[PubMed: 8990018]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<81::AID-HUMU18>3.0.CO;2-L]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Avramopoulos, D., Cox, T., Kraus, J. P., Chakravarti, A., Antonarakis, S. E.
|
|
<strong>Linkage mapping of the cystathionine beta-synthase (CBS) gene on human chromosome 21 using a DNA polymorphism in the 3-prime untranslated region.</strong>
|
|
Hum. Genet. 90: 566-568, 1993.
|
|
|
|
|
|
[PubMed: 8094069]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00217460]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bateman, A.
|
|
<strong>The structure of a domain common to archaebacteria and the homocystinuria disease protein.</strong>
|
|
Trends Biochem. Sci. 22: 12-13, 1997.
|
|
|
|
|
|
[PubMed: 9020585]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0968-0004(96)30046-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Behera, J., Kelly, K. E., Voor, M. J., Metreveli, N., Tyagi, S. C., Tyagi, N.
|
|
<strong>Hydrogen sulfide promotes bone homeostasis by balancing inflammatory cytokine signaling in CBS-deficient mice through an epigenetic mechanism.</strong>
|
|
Sci. Rep. 8: 15226, 2018.
|
|
|
|
|
|
[PubMed: 30323246]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41598-018-33149-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bross, P., Corydon, T. J., Andresen, B. S., Jorgensen, M. M., Bolund, L., Gregersen, N.
|
|
<strong>Protein misfolding and degradation in genetic diseases.</strong>
|
|
Hum. Mutat. 14: 186-198, 1999.
|
|
|
|
|
|
[PubMed: 10477427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<186::AID-HUMU2>3.0.CO;2-J]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chadefaux, B., Rethore, M. O., Raoul, O., Ceballos, I., Poissonnier, M., Gilgenkrantz, S., Allard, D.
|
|
<strong>Cystathionine beta synthase: gene dosage effect in trisomy 21.</strong>
|
|
Biochem. Biophys. Res. Commun. 128: 40-44, 1985.
|
|
|
|
|
|
[PubMed: 3157380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(85)91641-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chasse, J. F., Paly, E., Paris, D., Paul, V., Sinet, P. M., Kamoun, P., London, J.
|
|
<strong>Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs.</strong>
|
|
Biochem. Biophys. Res. Commun. 211: 826-832, 1995.
|
|
|
|
|
|
[PubMed: 7598711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1995.1886]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chasse, J. F., Paul, V., Escanez, R., Kamoun, P., London, J.
|
|
<strong>Human cystathionine beta-synthase: gene organization and expression of different 5-prime alternative splicing.</strong>
|
|
Mammalian Genome 8: 917-921, 1997.
|
|
|
|
|
|
[PubMed: 9383285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900611]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Franco, R. F., Elion, J., Lavinha, J., Krishnamoorthy, R., Tavella, M. H., Zago, M. A.
|
|
<strong>Heterogeneous ethnic distribution of the 844ins68 in the cystathionine beta-synthase gene.</strong>
|
|
Hum. Hered. 48: 338-342, 1998.
|
|
|
|
|
|
[PubMed: 9813456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000022826]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gallagher, P. M., Ward, P., Tan, S., Naughten, E., Kraus, J. P., Sellar, G. C., McConnell, D. J., Graham, I., Whitehead, A. S.
|
|
<strong>High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.</strong>
|
|
Hum. Mutat. 6: 177-180, 1995.
|
|
|
|
|
|
[PubMed: 7581402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380060211]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaustadnes, M., Ingerslev, J., Rutiger, N.
|
|
<strong>Prevalence of congenital homocystinuria in Denmark. (Letter)</strong>
|
|
New Eng. J. Med. 340: 1513 only, 1999.
|
|
|
|
|
|
[PubMed: 10328723]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199905133401915]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaustadnes, M., Rudiger, N., Rasmussen, K., Ingerslev, J.
|
|
<strong>Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.</strong>
|
|
Thromb. Haemost. 83: 554-558, 2000.
|
|
|
|
|
|
[PubMed: 10780316]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldstein, J. L., Campbell, B. K., Gartler, S. M.
|
|
<strong>Cystathionine synthetase activity in human lymphocytes: induction by phytohemagglutinin.</strong>
|
|
J. Clin. Invest. 51: 1034-1037, 1972.
|
|
|
|
|
|
[PubMed: 5014609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI106863]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gu, Z., Ramesh, V., Kozich, V., Korson, M. S., Kraus, J. P., Shih, V. E.
|
|
<strong>Identification of a molecular genetic defect in homocystinuria due to cystathionine beta-synthase deficiency. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49: 406 only, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gupta, S., Wang, L., Hua, X., Krijt, J., Kozich, V., Kruger, W. D.
|
|
<strong>Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice.</strong>
|
|
Hum. Mutat. 29: 1048-1054, 2008.
|
|
|
|
|
|
[PubMed: 18454451]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20773]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hu, F. L., Gu, Z., Kozich, V., Kraus, J. P., Ramesh, V., Shih, V. E.
|
|
<strong>Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.</strong>
|
|
Hum. Molec. Genet. 2: 1857-1860, 1993.
|
|
|
|
|
|
[PubMed: 7506602]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.11.1857]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janosik, M., Oliveriusova, J., Janosikova, B., Sokolova, J., Kraus, E., Kraus, J. P., Kozich, V.
|
|
<strong>Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria.</strong>
|
|
Am. J. Hum. Genet. 68: 1506-1513, 2001.
|
|
|
|
|
|
[PubMed: 11359213]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/320597]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kelly, P. J., Furie, K. L., Kistler, J. P., Barron, M., Picard, E. H., Mandell, R., Shih, V. E.
|
|
<strong>Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.</strong>
|
|
Neurology 60: 275-279, 2003.
|
|
|
|
|
|
[PubMed: 12552044]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000042479.55406.b3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kery, V., Poneleit, L., Meyer, J. D., Manning, M. C., Kraus, J. P.
|
|
<strong>Binding of pyridoxal 5-prime-phosphate to the heme protein human cystathionine beta-synthase.</strong>
|
|
Biochemistry 38: 2716-2724, 1999.
|
|
|
|
|
|
[PubMed: 10052942]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi981808n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, C. E., Gallagher, P. M., Guttormsen, A. B., Refsum, H., Ueland, P. M., Ose, L., Folling, I., Whitehead, A. S., Tsai, M. Y., Kruger, W. D.
|
|
<strong>Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.</strong>
|
|
Hum. Molec. Genet. 6: 2213-2221, 1997.
|
|
|
|
|
|
[PubMed: 9361025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.13.2213]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, Y. J., Rosenberg, L. E.
|
|
<strong>On the mechanism of pyridoxine responsive homocystinuria. II. Properties of normal and mutant cystathionine beta-synthase from cultured fibroblasts.</strong>
|
|
Proc. Nat. Acad. Sci. 71: 4821-4825, 1974.
|
|
|
|
|
|
[PubMed: 4531018]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.71.12.4821]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., Boers, G. H. J., Kraus, J. P., van den Heuvel, L. P. W. J., Cruysberg, J. R. M., Trijbels, F. J. M., Blom, H. J.
|
|
<strong>The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment.</strong>
|
|
Am. J. Hum. Genet. 65: 59-67, 1999.
|
|
|
|
|
|
[PubMed: 10364517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302439]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., Boers, G. H. J., Stevens, E. M. B., Renier, W. O., Kraus, J. P., Trijbels, F. J. M., van den Heuvel, L. P. W. J., Blom, H. J.
|
|
<strong>Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient.</strong>
|
|
J. Clin. Invest. 98: 285-289, 1996.
|
|
|
|
|
|
[PubMed: 8755636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118791]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kluijtmans, L. A. J., van den Heuvel, L. P. W. J., Boers, G. H. J., Frosst, P., Stevens, E. M. B., van Oost, B. A., den Heijer, M., Trijbels, F. J. M., Rozen, R., Blom, H. J.
|
|
<strong>Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease.</strong>
|
|
Am. J. Hum. Genet. 58: 35-41, 1996.
|
|
|
|
|
|
[PubMed: 8554066]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kozich, V., de Franchis, R., Kraus, J. P.
|
|
<strong>Molecular defect in a patient with pyridoxine-responsive homocystinuria.</strong>
|
|
Hum. Molec. Genet. 2: 815-816, 1993.
|
|
|
|
|
|
[PubMed: 8353501]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.6.815]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kozich, V., Kraus, J. P.
|
|
<strong>Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency.</strong>
|
|
Hum. Mutat. 1: 113-123, 1992.
|
|
|
|
|
|
[PubMed: 1301198]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380010206]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Janosik, M., Kozich, V., Mandell, R., Shih, V., Sperandeo, M. P., Sebastio, G., de Franchis, R., Andria, G., Kluijtmans, L. A. J., Blom, H., Boers, G. H. J., Gordon, R. B., Kamoun, P., Tsai, M. Y., Kruger, W. D., Koch, H. G., Ohura, T., Gaustadnes, M.
|
|
<strong>Cystathionine beta-synthase mutations in homocystinuria.</strong>
|
|
Hum. Mutat. 13: 362-375, 1999.
|
|
|
|
|
|
[PubMed: 10338090]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<362::AID-HUMU4>3.0.CO;2-K]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Le, K., Swaroop, M., Ohura, T., Tahara, T., Rosenberg, L. E., Roper, M. D., Kozich, V.
|
|
<strong>Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells.</strong>
|
|
Hum. Molec. Genet. 2: 1633-1638, 1993.
|
|
|
|
|
|
[PubMed: 7903580]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.10.1633]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kraus, J. P., Oliveriusova, J., Sokolova, J., Kraus, E., Vlcek, C., de Franchis, R., Maclean, K. N., Bao, L., Bukovska, G., Patterson, D., Paces, V., Ansorge, W., Kozich, V.
|
|
<strong>The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.</strong>
|
|
Genomics 52: 312-324, 1998.
|
|
|
|
|
|
[PubMed: 9790750]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1998.5437]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kraus, J. P.
|
|
<strong>Molecular basis of phenotype expression in homocystinuria.</strong>
|
|
J. Inherit. Metab. Dis. 17: 383-390, 1994.
|
|
|
|
|
|
[PubMed: 7967489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00711354]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kraus, J., Packman, S., Fowler, B., Rosenberg, L. E.
|
|
<strong>Purification and properties of cystathionine beta-synthase from human liver: evidence for identical subunits.</strong>
|
|
J. Biol. Chem. 253: 6523-6528, 1978.
|
|
|
|
|
|
[PubMed: 681363]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Cox, D. R.
|
|
<strong>A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 6614-6618, 1994.
|
|
|
|
|
|
[PubMed: 8022826]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.14.6614]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Cox, D. R.
|
|
<strong>A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.</strong>
|
|
Hum. Molec. Genet. 4: 1155-1161, 1995.
|
|
|
|
|
|
[PubMed: 8528202]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.7.1155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kruger, W. D., Wang, L., Jhee, K. H., Singh, R. H., Elsas, L. J., II.
|
|
<strong>Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.</strong>
|
|
Hum. Mutat. 22: 434-441, 2003.
|
|
|
|
|
|
[PubMed: 14635102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10290]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kruger, W. D.
|
|
<strong>Cystathionine beta-synthase deficiency: of mice and men.</strong>
|
|
Molec. Genet. Metab. 121: 199-205, 2017.
|
|
|
|
|
|
[PubMed: 28583326]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2017.05.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, S.-J., Lee, D. H., Yoo, H.-W., Koo, S. K., Park, E.-S., Park, J.-W., Lim, H. G., Jung, S.-C.
|
|
<strong>Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria.</strong>
|
|
J. Hum. Genet. 50: 648-654, 2005.
|
|
|
|
|
|
[PubMed: 16205833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-005-0312-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maclean, K. N., Gaustadnes, M., Oliveriusova, J., Janosik, M., Kraus, E., Kozich, V., Kery, V., Skovby, F., Rudiger, N., Ingerslev, J., Stabler, S. P., Allen, R. H., Kraus, J. P.
|
|
<strong>High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations.</strong>
|
|
Hum. Mutat. 19: 641-655, 2002.
|
|
|
|
|
|
[PubMed: 12007221]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10089]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Munke, M., Kraus, J. P., Ohura, T., Francke, U.
|
|
<strong>The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17.</strong>
|
|
Am. J. Hum. Genet. 42: 550-559, 1988.
|
|
|
|
|
|
[PubMed: 2894761]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Munke, M., Kraus, J., Watkins, P., Tanzi, R., Gusella, J., Millington Ward, A., Watson, M., Francke, U.
|
|
<strong>Homocystinuria gene on human chromosome 21 mapped with cloned cystathionine beta-synthase probe and in situ hybridization of other chromosome 21 probes. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 40: 706-707, 1985.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Namekata, K., Enokido, Y., Ishii, I., Nagai, Y., Harada, T., Kimura, H.
|
|
<strong>Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia.</strong>
|
|
J. Biol. Chem. 279: 52961-52969, 2004.
|
|
|
|
|
|
[PubMed: 15466479]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M406820200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pogribna, M., Melnyk, S., Pogribny, I., Chango, A., Yi, P., James, S. J.
|
|
<strong>Homocysteine metabolism in children with Down syndrome: in vitro modulation.</strong>
|
|
Am. J. Hum. Genet. 69: 88-95, 2001.
|
|
|
|
|
|
[PubMed: 11391481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/321262]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robert, K., Chasse, J.-F., Santiard-Baron, D., Vayssettes, C., Chabli, A., Aupetit, J., Maeda, N., Kamoun, P., London, J., Janel, N.
|
|
<strong>Altered gene expression in liver from a murine model of hyperhomocysteinemia.</strong>
|
|
J. Biol. Chem. 278: 31504-31511, 2003.
|
|
|
|
|
|
[PubMed: 12799373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M213036200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robert, K., Vialard, F., Thiery, E., Toyama, K., Sinet, P.-M., Janel, N., London, J.
|
|
<strong>Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain.</strong>
|
|
J. Histochem. Cytochem. 51: 363-371, 2003.
|
|
|
|
|
|
[PubMed: 12588964]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1177/002215540305100311]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, J. W., Hawley, S. A., Green, K. A., Anis, M., Stewart, G., Scullion, G. A., Norman, D. G., Hardie, D. G.
|
|
<strong>CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.</strong>
|
|
J. Clin. Invest. 113: 274-284, 2004.
|
|
|
|
|
|
[PubMed: 14722619]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI19874]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sebastio, G., Sperandeo, M. P., Panico, M., de Franchis, R., Kraus, J. P., Andria, G.
|
|
<strong>The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.</strong>
|
|
Am. J. Hum. Genet. 56: 1324-1333, 1995.
|
|
|
|
|
|
[PubMed: 7762555]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sebastio, G.
|
|
<strong>Personal Communication.</strong>
|
|
Padua, Italy 3/20/1997.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shan, X., Dunbrack, R. L., Jr., Christopher, S. A., Kruger, W. D.
|
|
<strong>Mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient-derived mutations in cis.</strong>
|
|
Hum. Molec. Genet. 10: 635-643, 2001.
|
|
|
|
|
|
[PubMed: 11230183]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.6.635]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shan, X., Kruger, W. D.
|
|
<strong>Correction of disease-causing CBS mutations in yeast.</strong>
|
|
Nature Genet. 19: 91-93, 1998.
|
|
|
|
|
|
[PubMed: 9590298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0598-91]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shih, V. E., Fringer, J. M., Mandell, R., Kraus, J. P., Berry, G. T., Heidenreich, R. A., Korson, M. S., Levy, H. L., Ramesh, V.
|
|
<strong>A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype.</strong>
|
|
Am. J. Hum. Genet. 57: 34-39, 1995.
|
|
|
|
|
|
[PubMed: 7611293]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skovby, F., Gaustadnes, M., Mudd, S. H.
|
|
<strong>A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency.</strong>
|
|
Molec. Genet. Metab. 99: 1-3, 2010.
|
|
|
|
|
|
[PubMed: 19819175]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2009.09.009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skovby, F., Krassikoff, N., Francke, U.
|
|
<strong>Assignment of the gene for cystathionine beta-synthase (CBS) to human chromosome 21 in somatic cell hybrids. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 585 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skovby, F., Krassikoff, N., Francke, U.
|
|
<strong>Assignment of the gene for cystathionine beta-synthase to human chromosome 21 in somatic cell hybrids.</strong>
|
|
Hum. Genet. 65: 291-294, 1984.
|
|
|
|
|
|
[PubMed: 6583157]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00286520]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skovby, F., Kraus, J. P., Rosenberg, L. E.
|
|
<strong>Homocystinuria: biogenesis of cystathionine beta-synthase subunits in cultured fibroblasts and in an in vitro translation system programmed with fibroblast messenger RNA.</strong>
|
|
Am. J. Hum. Genet. 36: 452-459, 1984.
|
|
|
|
|
|
[PubMed: 6711564]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sperandeo, M. P., de Franchis, R., Andria, G., Sebastio, G.
|
|
<strong>A 68-bp insertion found in a homocystinuric patient is a common variant and is skipped by alternative splicing of the cystathionine beta-synthase mRNA. (Letter)</strong>
|
|
Am. J. Hum. Genet. 59: 1391-1393, 1996.
|
|
|
|
|
|
[PubMed: 8940285]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sperandeo, M. P., Panico, M., Pepe, A., Candito, M., de Franchis, R., Kraus, J. P., Andria, G., Sebastio, G.
|
|
<strong>Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11.</strong>
|
|
J. Inherit. Metab. Dis. 18: 211-214, 1995.
|
|
|
|
|
|
[PubMed: 7564249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00711769]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stubbs, L., Kraus, J., Lehrach, H.
|
|
<strong>The alpha-A-crystallin and cystathionine beta-synthase genes are physically very closely linked in proximal mouse chromosome 17.</strong>
|
|
Genomics 7: 284-288, 1990.
|
|
|
|
|
|
[PubMed: 2347594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90553-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, M. Y., Bignell, M., Schwichtenberg, K., Hanson, N. Q.
|
|
<strong>High prevalence of a mutation in the cystathionine beta-synthase gene.</strong>
|
|
Am. J. Hum. Genet. 59: 1262-1267, 1996.
|
|
|
|
|
|
[PubMed: 8940271]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urreizti, R., Asteggiano, C., Bermudez, M., Cordoba, A., Szlago, M., Grosso, C., de Kremer, R. D., Vilarinho, L., D'Almeida, V., Martinez-Pardo, M., Pena-Quintana, L., Dalmau, J., Bernal, J., Briceno, I., Couce, M. L., Rodes, M., Vilaseca, M. A., Balcells, S., Grinberg, D.
|
|
<strong>The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.</strong>
|
|
J. Hum. Genet. 51: 305-313, 2006. Note: Erratum: J. Hum. Genet. 52: 388-389, 2007.
|
|
|
|
|
|
[PubMed: 16479318]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-006-0362-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L., Chen, X., Tang, B., Hua, X., Klein-Szanto, A., Kruger, W. D.
|
|
<strong>Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model.</strong>
|
|
Hum. Molec. Genet. 14: 2201-2208, 2005.
|
|
|
|
|
|
[PubMed: 15972722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi224]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watanabe, M., Osada, J., Aratani, Y., Kluckman, K., Reddick, R., Malinow, M. R., Maeda, N.
|
|
<strong>Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 1585-1589, 1995.
|
|
|
|
|
|
[PubMed: 7878023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.92.5.1585]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
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|
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Contributors:
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<span class="mim-text-font">
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Bao Lige - updated : 09/09/2022<br>Carol A. Bocchini - updated : 07/18/2017
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Creation Date:
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