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Entry
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- *156570 - 5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE S-METHYLTRANSFERASE; MTR
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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">*156570</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</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/156570">Table View</a>
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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>
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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>
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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=ENSG00000116984;t=ENST00000366577" 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=4548" 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=156570" 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=ENSG00000116984;t=ENST00000366577" 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_000254,NM_001291939,NM_001291940,NM_001410942,XM_005273141,XM_011544194,XM_017001329,XM_017001330,XM_047421182,XM_047421183,XM_047421185,XM_047421186,XM_047421187" 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_000254" 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=156570" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=01136&isoform_id=01136_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/MTR" 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/1763269,1923221,2160699,2842762,34365461,119590472,119590473,120660446,169790923,194376830,194389568,219519019,219520194,223460110,530366222,633257781,633257783,767912450,1034558712,1034558715,2217267632,2217267634,2217267638,2217267640,2217267642,2287780829,2462509409,2462509411,2462509413,2462509415,2462509417,2462509419,2462509421,2462509423,2462509425" 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/Q99707" 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=4548" 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=ENSG00000116984;t=ENST00000366577" 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=MTR" 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=MTR" 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+4548" 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/MTR" 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:4548" 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/4548" 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=chr1&hgg_gene=ENST00000366577.10&hgg_start=236795281&hgg_end=236903981&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:7468" 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:7468" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=156570[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">
|
|
<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=156570[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/MTR/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/ENSG00000116984" 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=MTR" 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=MTR" 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=MTR" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://databases.lovd.nl/genomed/home.php?select_db=MTR" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MTR&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/PA31272" 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:7468" 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://www.mousephenotype.org/data/genes/MGI:894292" 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/MTR#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:894292" 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/4548/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=4548" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00010988;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-031001-5" 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="mimCellLines">
|
|
<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</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="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:156570" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</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">
|
|
<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:4548" 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=MTR&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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156570
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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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5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE S-METHYLTRANSFERASE; MTR
|
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</span>
|
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
TETRAHYDROPTEROYLGLUTAMATE METHYLTRANSFERASE<br />
|
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METHIONINE SYNTHASE; MS
|
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</span>
|
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</h4>
|
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</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MTR" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MTR</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1829?start=-3&limit=10&highlight=1829">1q43</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:236795281-236903981&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'})">1:236,795,281-236,903,981</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<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>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=601634,250940" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1829?start=-3&limit=10&highlight=1829">
|
|
1q43
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
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<p>The remethylation of homocysteine to form methionine is catalyzed by the cytoplasmic enzyme 5-methyltetrahydrofolate-homocysteine S-methyltransferase (<a href="https://enzyme.expasy.org/EC/2.1.1.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.1.1.13</a>), which is also called methionine synthase. This enzyme requires methylcobalamin (MeCbl), a derivative of cobalamin, or vitamin B12, for activity (summary by <a href="#8" class="mim-tip-reference" title="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968735" 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="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al. (1996)</a> described the isolation and characterization of the human methionine synthase (MTR) cDNA. To isolate the MTR cDNA, they took advantage of the evolutionary conservation of MTR and identified sequence blocks of the homologous E. coli METH gene that showed high DNA homology with sequence blocks of MTR from C. elegans. They then designed primers for 4 regions of high DNA homology and used these to PCR amplify first strand cDNA from human lymphoblastoid cell lines. One of the primer pairs amplified a 350-bp fragment that on sequence analysis had 64% homology with the C. elegans protein. The 350-bp PCR fragment was used to isolate a clone from a hepatoma cDNA library. This clone extended from the middle of the predicted open reading frame (ORF) to a few hundred bp upstream of the predicted start codon. Additional clones were identified in the EST database by searching with the C-terminal ends of the C. elegans and the E. coli proteins. <a href="#8" class="mim-tip-reference" title="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al. (1996)</a> reported that the human MTR gene encodes a protein of 1,265 amino acids. The MTR cDNA probes detected 7.5- and 10-kb transcripts in a range of different human tissues. The human probe hybridized to a single 5-kb message in mouse tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968735" 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>Independently and simultaneously, <a href="#7" class="mim-tip-reference" title="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> sought to clone the human MTR gene by identifying 4 regions of homology among methionine synthases of 3 bacteria and C. elegans. They utilized sequence in these regions to design degenerate oligonucleotides to derive PCR products from reverse transcribed cDNA. These PCR products were then used to clone the human methionine synthase gene. <a href="#7" class="mim-tip-reference" title="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> reported that the methionine synthase gene encodes a 1,265-amino acid protein. They concluded that the cDNA that they had isolated represented methionine synthase on the basis of sequence homology and by identifying mutations in cblG patients with deficiency of enzyme activity. The most striking sequence homology was found in 4 boxes of 9 to 13 amino acids. Box 2 contains 13 consecutive residues which were identical in all known methionine synthases. Sequences in box 2 correspond to part of the cobalamin binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968737" 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>MTR cDNAs were isolated independently by <a href="#2" class="mim-tip-reference" title="Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B. <strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong> J. Biol. Chem. 272: 3628, and 3634, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9013615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9013615</a>]" pmid="9013615">Chen et al. (1997)</a> using RT-PCR with primers based on conserved regions of E. coli and C. elegans methionine synthetase. In addition to the major 8- and 10-kb mRNAs, <a href="#2" class="mim-tip-reference" title="Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B. <strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong> J. Biol. Chem. 272: 3628, and 3634, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9013615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9013615</a>]" pmid="9013615">Chen et al. (1997)</a> detected a minor 4.4-kb mRNA and other minor, partially spliced larger mRNAs on Northern blots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9013615" 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="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> characterized the structure of the MTR gene, thereby identifying exon-intron boundaries and enabling amplification of each of the 33 exons of the gene from genomic DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the studies of <a href="#9" class="mim-tip-reference" title="Mellman, I. S., Lin, P.-F., Ruddle, F. H., Rosenberg, L. E. <strong>Genetic control of cobalamin binding in normal and mutant cells: assignment of the gene for 5-methyltetrahydrofolate: L-homocysteine S-methyltransferase to human chromosome 1.</strong> Proc. Nat. Acad. Sci. 76: 405-409, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/284356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">284356</a>] [<a href="https://doi.org/10.1073/pnas.76.1.405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="284356">Mellman et al. (1979)</a>, when extracts prepared from cultured fibroblasts grown in medium containing cobalt-57-labeled cobalamin were analyzed by polyacrylamide gel, intracellular radioactivity was found to be associated with methionine synthase. For this reason and also because rodent and human forms of the enzyme were electrophoretically distinguishable, these workers could use binding to identify the presence of human methyltransferase (MTR) in rodent-human somatic cell hybrids. By this approach, they assigned the methyltransferase gene to chromosome 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=284356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al. (1996)</a> used the cDNA probes for chromosome mapping by in situ hybridization studies. They reported that the MTR gene maps to 1q42.3-1q44. <a href="#19" class="mim-tip-reference" title="Zhang, Z.-X., Leclerc, D., Gravel, R., Rozen, R. <strong>The methionine synthase (Mtr) gene maps to proximal mouse chromosome 13.</strong> Mammalian Genome 8: 787-797, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321480</a>] [<a href="https://doi.org/10.1007/s003359900570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9321480">Zhang et al. (1997)</a> found that the mouse Mtr gene maps to proximal chromosome 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8968735+9321480" 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="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> used cDNA probes and fluorescence in situ hybridization to assign the methionine synthase gene to chromosome 1q43. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968737" 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="Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B. <strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong> J. Biol. Chem. 272: 3628, and 3634, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9013615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9013615</a>]" pmid="9013615">Chen et al. (1997)</a> confirmed the map position of the MTR gene to 1q42.3-q43 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9013615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using purified recombinant human proteins, <a href="#17" class="mim-tip-reference" title="Yamada, K., Gravel, R. A., Toraya, T., Matthews, R. G. <strong>Human methionine synthase reductase is a molecular chaperone for human methionine synthase.</strong> Proc. Nat. Acad. Sci. 103: 9476-9481, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16769880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16769880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16769880[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/10.1073/pnas.0603694103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16769880">Yamada et al. (2006)</a> found that MTRR maintained MTR activity at a 1:1 stoichiometric ratio. In the presence of MTRR and NADPH, holoenzyme formation from apoMTR and methylcobalamin was significantly enhanced due to stabilization of apoMTR in the presence of MTRR. MTRR was also able to reduce aquacobalamin to cob(II)alamin in the presence of NADPH, which stimulated conversion of apoMTR and aquacobalamin to holoMTR. <a href="#17" class="mim-tip-reference" title="Yamada, K., Gravel, R. A., Toraya, T., Matthews, R. G. <strong>Human methionine synthase reductase is a molecular chaperone for human methionine synthase.</strong> Proc. Nat. Acad. Sci. 103: 9476-9481, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16769880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16769880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16769880[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/10.1073/pnas.0603694103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16769880">Yamada et al. (2006)</a> concluded that MTRR serves as a chaperone for MTR and as an aquacobalamin reductase, rather than acting solely in reductive activation of MTR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16769880" 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><strong><em>Homocystinuria-Megaloblastic Anemia, cblG Complementation Type</em></strong></p><p>
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<a href="#8" class="mim-tip-reference" title="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al. (1996)</a> reviewed the role of MTR in homocysteine metabolism. They noted that loss-of-function mutations in MTR would cause increased levels of plasma homocysteine. They noted also that defects in MTR activity may play a role in tumorigenesis, since approximately 50% of tumor cells require the addition of exogenous methionine for growth and homocysteine and folate cannot replace methionine. <a href="#8" class="mim-tip-reference" title="Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D. <strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong> Hum. Molec. Genet. 5: 1851-1858, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968735">Li et al. (1996)</a> concluded that since methionine can only be synthesized by methylation of homocysteine, the inability of tumor cells to grow on homocysteine suggests that they have a defect in methionine synthase. With that in mind, <a href="#5" class="mim-tip-reference" title="Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R. <strong>Defects in human methionine synthase in cblG patients.</strong> Hum. Molec. Genet. 5: 1859-1865, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968736">Gulati et al. (1996)</a> analyzed the molecular basis for methionine synthase deficiency in cell lines derived from 2 patients with cblG disorder (HMAG; <a href="/entry/250940">250940</a>). The 79/76 cell line (from a patient with severe neurologic dysfunction and homocystinuria but no megaloblastic anemia) had low levels of MTR activity and a diminished level of MTR mRNA. In the WG1892 cell line (from a patient with mental retardation, macrocytic anemia, and homocystinuria), they detected a pro1173-to-leu mutation (<a href="#0001">156570.0001</a>) and a 3-bp deletion leading to loss of ile881 (<a href="#0002">156570.0002</a>). <a href="#5" class="mim-tip-reference" title="Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R. <strong>Defects in human methionine synthase in cblG patients.</strong> Hum. Molec. Genet. 5: 1859-1865, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968736">Gulati et al. (1996)</a> stated that the onset of symptoms was within the first 4 months of life for each patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8968736+8968735" 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="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> identified 2 mutations (<a href="#0002">156570.0002</a>, <a href="#0003">156570.0003</a>) in the vicinity of the cobalamin-binding domain in cell lines derived from patients with cblG disease, one of whom (WG1892) was also reported by <a href="#5" class="mim-tip-reference" title="Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R. <strong>Defects in human methionine synthase in cblG patients.</strong> Hum. Molec. Genet. 5: 1859-1865, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968736">Gulati et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8968736+8968737" 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 panel of 21 patients with methylcobalamin deficiency G (cblG) disorder, <a href="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> identified 13 novel mutations. These included 5 deletions and 2 nonsense mutations that resulted in synthesis of truncated proteins that lacked portions critical for enzyme function. In addition, a previously described missense mutation, P1173L (<a href="#0001">156570.0001</a>), was detected in 16 patients in an expanded panel of 24 patients with cblG. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C-to-T transition in a CpG island, has occurred on at least 2 separate genetic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" 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>Associations Pending Confirmation</em></strong></p><p>
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Evaluation of the relationship between variation in genes that are involved in the folate-homocysteine metabolic axis and the risk of neural tube defects (<a href="/entry/601634">601634</a>) is complicated by the potential involvement of both the maternal and embryonic genotypes in determination of disease risk. <a href="#4" class="mim-tip-reference" title="Doolin, M.-T., Barbaux, S., McDonnell, M., Hoess, K., Whitehead, A. S., Mitchell, L. E. <strong>Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.</strong> Am. J. Hum. Genet. 71: 1222-1226, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12375236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12375236</a>] [<a href="https://doi.org/10.1086/344209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12375236">Doolin et al. (2002)</a> designed a study to address questions regarding both maternal and embryonic genetic risk factors for spina bifida by use of the 2-step transmission/disequilibrium test. Analysis of data on variants of 2 genes involved in homocysteine remethylation/methionine biosynthesis, viz., the MTR 2756A-G (<a href="#0008">156570.0008</a>) and methionine synthase reductase (MTRR, or MSR; <a href="/entry/602568">602568</a>) 66A-G (<a href="/entry/602568#0003">602568.0003</a>) polymorphisms, provided evidence that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype. For both variants, the risk of having a child with spina bifida appeared to increase with the number of high-risk alleles in the maternal genotype. The findings highlighted the importance of considering both the maternal and embryonic genotypes when evaluating putative spina bifida susceptibility loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12375236" 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="#18" class="mim-tip-reference" title="Zhang, Y., Zhang, M., Niu, T., Xu, X., Zhu, G., Huo, Y., Chen, C., Wang, X., Xing, H., Peng, S., Huang, A., Hong, X., Xu, X. <strong>D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.</strong> J. Hum. Genet. 49: 296-301, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148588</a>] [<a href="https://doi.org/10.1007/s10038-004-0149-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15148588">Zhang et al. (2004)</a> studied 726 Chinese patients with hypertension (<a href="/entry/145500">145500</a>) and their families for the association between the asp919-to-glu (D919G) polymorphism of the MTR gene and the antihypertensive effect of the angiotensin-converting enzyme (ACE; <a href="/entry/106180">106180</a>) inhibitor benazepril. Compared to the 919D allele, both population-based and family-based association tests demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15148588" 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="Mostowska, A., Hozyasz, K. K., Jagodzinski, P. P. <strong>Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population.</strong> Clin. Genet. 69: 512-517, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712703</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00618.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16712703">Mostowska et al. (2006)</a> found increased frequency of the 2756G allele among 122 Polish mothers of children with orofacial clefts (see <a href="/entry/119530">119530</a>). Mothers with the GA or GG genotypes had an odds ratio of 2.195 for having a child with cleft lip/palate compared to mothers with the AA genotype. In another study of 174 Polish children with cleft lip/palate or cleft lip only, <a href="#11" class="mim-tip-reference" title="Mostowska, A., Hozyasz, K. K., Wojcicki, P., Dziegelewska, M., Jagodzinski, P. P. <strong>Associations of folate and choline metabolism gene polymorphisms with orofacial clefts.</strong> J. Med. Genet. 47: 809-815, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19737740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19737740</a>] [<a href="https://doi.org/10.1136/jmg.2009.070029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19737740">Mostowska et al. (2010)</a> found no association with SNPs in the MTR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16712703+19737740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=156570[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<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> rs121913578 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913578;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/rs121913578?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=rs121913578" 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=rs121913578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a cell line (WG1892) from a CblG (HMAG; <a href="/entry/250940">250940</a>) patient with mental retardation, macrocytic anemia, and homocystinuria, <a href="#5" class="mim-tip-reference" title="Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R. <strong>Defects in human methionine synthase in cblG patients.</strong> Hum. Molec. Genet. 5: 1859-1865, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968736">Gulati et al. (1996)</a> detected compound heterozygous mutations in the MTR gene: a 3804C-T transition resulting in a pro1173-to-leu (P1173L) amino acid substitution, and a 3-bp deletion (2926del3; <a href="#0002">156570.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968736" 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 panel of 24 patients with the cblG disorder, <a href="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> found the P1173L mutation in 16 patients. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C-to-T transition in the CpG island, has occurred on at least 2 separate genetic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" 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">rs797044443 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044443;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=rs797044443" 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=rs797044443" 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 3-bp deletion in the MTR gene (2926del3) that was found in compound heterozygous state in a cell line (WG1892) from a CblG (HMAG; <a href="/entry/250940">250940</a>) patient by <a href="#5" class="mim-tip-reference" title="Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R. <strong>Defects in human methionine synthase in cblG patients.</strong> Hum. Molec. Genet. 5: 1859-1865, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968736">Gulati et al. (1996)</a>, see <a href="#0001">156570.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968736" 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="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> also reported this mutation in the WG1892 cell line. They stated that the patient was a Caucasian male who was diagnosed at age 4 years with developmental delay, tremors, gait instability, megaloblastic anemia, and homocystinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968737" 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> rs121913579 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913579;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/rs121913579?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=rs121913579" 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=rs121913579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#7" class="mim-tip-reference" title="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> identified a 2758C-G point mutation in heterozygous form in the MTR gene of cblG (<a href="/entry/250940">250940</a>) patient cell line WG2290. It resulted in a his920-to-asp (H920D) substitution and loss of a Sau96I restriction site. The second mutation in this cell line was not identified. This cell line was derived from a Caucasian male who presented at 3 months of age with failure to thrive, severe eczema, megaloblastic anemia, homocystinuria, and methylmalonic aciduria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968737" 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">rs1661117141 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1661117141;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=rs1661117141" 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=rs1661117141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a brother and sister with the cblG variant form of methionine synthase deficiency (<a href="/entry/250940">250940</a>), <a href="#16" class="mim-tip-reference" title="Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A. <strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong> Am. J. Hum. Genet. 63: 409-414, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683607</a>] [<a href="https://doi.org/10.1086/301976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683607">Wilson et al. (1998)</a> identified compound heterozygosity for 2 null mutations in the MTR gene: an A-to-G substitution at position -166 of intron 3, resulting in a 165-bp insertion and premature termination, and a 2-bp deletion (2112delTC; <a href="#0005">156570.0005</a>), resulting in a frameshift and premature termination. The patients had a severe disorder with early onset and psychomotor retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683607" 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">rs797044444 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044444;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=rs797044444" 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=rs797044444" 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 2-bp deletion in the MTR gene (2112delTC) that was found in compound heterozygous state in a brother and sister with the cblG variant form of methionine synthase deficiency (<a href="/entry/250940">250940</a>) by <a href="#16" class="mim-tip-reference" title="Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A. <strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong> Am. J. Hum. Genet. 63: 409-414, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683607</a>] [<a href="https://doi.org/10.1086/301976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683607">Wilson et al. (1998)</a>, see <a href="#0004">156570.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a boy with the cblG variant form of methionine synthase deficiency (<a href="/entry/250940">250940</a>), <a href="#16" class="mim-tip-reference" title="Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A. <strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong> Am. J. Hum. Genet. 63: 409-414, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683607</a>] [<a href="https://doi.org/10.1086/301976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683607">Wilson et al. (1998)</a> found compound heterozygosity for 2 null mutations of the MTR gene. One was a 1-bp insertion, 3378insA (<a href="#0007">156570.0007</a>), which resulted in a frameshift and a downstream stop codon. The other was a splice site mutation which resulted in 2 different insertions in the mRNA: 1 of 78 bp and another of 128 bp, beginning after lys203. The 78-bp insertion was found to be a truncated version of the 128-bp insertion, missing the last 50 bp. By means of genomic sequencing, the insertions were discovered to be the result of a G-to-A substitution near the center of the intron after exon 6 that created a single cryptic 3-prime acceptor splice site. For each insert, a cryptic 5-prime donor splice site was recruited to complete the new exon, 1 at 78 bp and the other at 128 bp downstream of the mutation. Neither of the newly created 5-prime donor sites was preferred since the 2 transcripts appeared to occur in equal amounts. An in-frame stop codon occurred 9 bp into the insertions. The patient presented with short stature, failure to thrive, progressive weakness, hypotonia, ocular nystagmus, jaundice, feeding difficulties, and diarrhea at 7 to 10 weeks of age (<a href="#15" class="mim-tip-reference" title="Wildin, R. S., Scott, C. R. <strong>Cbl-G: presentation, treatment, and prolonged followup in a patient with absence of methionine synthase. (Abstract)</strong> Am. J. Hum. Genet. 51: A357 only, 1992."None>Wildin and Scott, 1992</a>). He had severe megaloblastic anemia and neutropenia, homocysteinemia, hypomethioninemia, and formiminoglutamic aciduria without methylmalonic aciduria, which led to the diagnosis of a defect in methionine synthesis. Treatment resulted in improved metabolite levels, improvement of tone, and reduction of nystagmus, but poor growth, developmental delay, feeding difficulties requiring a gastrostomy, persistent anemia, and immunologic deficits were present at age 4 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683607" 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>For discussion of the 1-bp insertion in the MTR gene (3378insA) that was found in compound heterozygous state in a patient with the cblG variant form of methionine synthase deficiency (<a href="/entry/250940">250940</a>) by <a href="#16" class="mim-tip-reference" title="Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A. <strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong> Am. J. Hum. Genet. 63: 409-414, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683607</a>] [<a href="https://doi.org/10.1086/301976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683607">Wilson et al. (1998)</a>, see <a href="#0006">156570.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683607" 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> rs1805087 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1805087;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/rs1805087?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=rs1805087" 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=rs1805087" 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=RCV000015355 OR RCV000126868 OR RCV000144923 OR RCV000398009 OR RCV001519615 OR RCV001812069 OR RCV003982899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015355, RCV000126868, RCV000144923, RCV000398009, RCV001519615, RCV001812069, RCV003982899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015355...</a>
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<p><a href="#7" class="mim-tip-reference" title="Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A. <strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong> Hum. Molec. Genet. 5: 1867-1874, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968737">Leclerc et al. (1996)</a> and <a href="#2" class="mim-tip-reference" title="Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B. <strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong> J. Biol. Chem. 272: 3628, and 3634, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9013615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9013615</a>]" pmid="9013615">Chen et al. (1997)</a> identified a common 2756A-G polymorphism of the MTR gene, resulting in the conversion of an aspartic acid residue to a glycine residue. <a href="#3" class="mim-tip-reference" title="Christensen, B., Arbour, L., Tran, P., Leclerc, D., Sabbaghian, N., Platt, R., Gilfix, B. M., Rosenblatt, D. S., Gravel, R. A., Forbes, P., Rozen, R. <strong>Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects.</strong> Am. J. Med. Genet. 84: 151-157, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323741</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<151::aid-ajmg12>3.0.co;2-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10323741">Christensen et al. (1999)</a> studied this polymorphism and the 677C-T polymorphism of the MTHFR gene (<a href="/entry/607093#0003">607093.0003</a>) in 56 patients with spina bifida (see <a href="/entry/601634">601634</a>), 62 mothers of the patients, 97 children without neural tube defects (controls), and 90 mothers of controls. The 2756G allele was associated with a decreased odds ratio; none of the cases and only 10% of controls were homozygous for this variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9013615+10323741+8968737" 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>Aberrant DNA methylation is a common feature of human neoplasia. <a href="#12" class="mim-tip-reference" title="Paz, M. F., Avila, S., Fraga, M. F., Pollan, M., Capella, G., Peinado, M. A., Sanchez-Cespedes, M., Herman, J. G., Esteller, M. <strong>Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors.</strong> Cancer Res. 62: 4519-4524, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12154064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12154064</a>]" pmid="12154064">Paz et al. (2002)</a> studied interindividual inherited susceptibility to the epigenetic processes of CpG island hypermethylation and global genomic hypomethylation, which are observed simultaneously in cancer cells. They genotyped 233 patients with colorectal, breast, or lung tumors for 4 germline variants in 3 key genes involved in the metabolism of the methyl group. A positive association of aberrant methylation was found with homozygosity for the MTR 2756G allele as well as with the 677T allele of the MTHFR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12154064" 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="Doolin, M.-T., Barbaux, S., McDonnell, M., Hoess, K., Whitehead, A. S., Mitchell, L. E. <strong>Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.</strong> Am. J. Hum. Genet. 71: 1222-1226, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12375236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12375236</a>] [<a href="https://doi.org/10.1086/344209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12375236">Doolin et al. (2002)</a> analyzed data on this polymorphism and the A66G polymorphism of the methionine synthase reductase gene (<a href="/entry/602568#0003">602568.0003</a>) and concluded that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype. For both variants, the risk of having a child with spina bifida appeared to increase with the number of high-risk alleles in the maternal genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12375236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bosco, P., Gueant-Rodriguez, R. M., Anello, G., Barone, C., Namour, F., Caraci, F., Romano, A., Romano, C., Gueant, J. L. <strong>Methionine synthase (MTR) 2756 (A-G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are 3 risk factors for having a child with Down syndrome.</strong> Am. J. Med. Genet. 121A: 219-224, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923861</a>] [<a href="https://doi.org/10.1002/ajmg.a.20234" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923861">Bosco et al. (2003)</a> studied the influence of the polymorphisms MTHFR 677C-T (<a href="/entry/607093#0003">607093.0003</a>) and 1298A-C (<a href="/entry/607093#0004">607093.0004</a>), MTR 2756A-G, and MTRR 66A-G (<a href="/entry/602568#0003">602568.0003</a>) on the risk of being a Down syndrome (DS; <a href="/entry/190685">190685</a>) case or having a DS child (case mother). Plasma homocysteine and other factors were likewise studied. They found that after adjustment for age, total homocysteine and MTR 2756 AG/GG genotype were significant risk factors for having a DS child, with odds ratio (OR) of 6.7 and 3.5, respectively. The MTR 2756 AG/GG genotype increased significantly the risk of being a DS case, with an OR of 3.8. Double heterozygosity for MTR 2756 AG/MTRR 66 AG was the single combined genotype that was a significant risk factor for having a DS child, with an OR estimated at 5.0, after adjustment for total homocysteine level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923861" 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> rs121913580 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913580;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/rs121913580?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=rs121913580" 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=rs121913580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a cell line (WG1975) from a patient with cblG disease (<a href="/entry/250940">250940</a>), <a href="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> identified a 1753C-T transition in the MTR gene, resulting in an arg585-to-ter (R585X) substitution. The mutation was predicted to result in synthesis of a truncated protein that lacked portions critical for enzyme function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" 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">rs121913581 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913581;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=rs121913581" 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=rs121913581" 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=RCV000015357" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015357" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015357</a>
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<p>In a cell line (WG2292) from a patient with cblG disease (<a href="/entry/250940">250940</a>), <a href="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> identified a 3613G-T transversion in the MTR gene, resulting in a glu1204-to-ter (E1204X) substitution. The mutation was predicted to result in synthesis of a truncated protein that lacked portions critical for enzyme function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" 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-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
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MTR, ALA410PRO
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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> rs121913582 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913582;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/rs121913582?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=rs121913582" 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=rs121913582" 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=RCV000015358 OR RCV004525853 OR RCV005007853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015358, RCV004525853, RCV005007853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015358...</a>
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<p>In a cell line (WG2009) from a patient with cblG disease (<a href="/entry/250940">250940</a>), <a href="#14" class="mim-tip-reference" title="Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S. <strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong> Am. J. Hum. Genet. 71: 143-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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/10.1086/341354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068375">Watkins et al. (2002)</a> identified a 1228G-C transversion in the MTR gene, resulting in an ala410-to-pro (A410P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068375" 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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<span class="mim-font">
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<strong>See Also:</strong>
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<a href="#Kvittingen1997" class="mim-tip-reference" title="Kvittingen, E. A., Spangen, S., Lindemans, J., Fowler, B. <strong>Methionine synthase deficiency without megaloblastic anaemia.</strong> Europ. J. Pediat. 156: 925-930, 1997.">Kvittingen et al. (1997)</a>; <a href="#Watkins1988" class="mim-tip-reference" title="Watkins, D., Rosenblatt, D. S. <strong>Genetic heterogeneity among patients with methylcobalamin deficiency.</strong> J. Clin. Invest. 81: 1690-1694, 1988.">Watkins and Rosenblatt (1988)</a>
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<strong>REFERENCES</strong>
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<a id="Bosco2003" class="mim-anchor"></a>
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Bosco, P., Gueant-Rodriguez, R. M., Anello, G., Barone, C., Namour, F., Caraci, F., Romano, A., Romano, C., Gueant, J. L.
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<strong>Methionine synthase (MTR) 2756 (A-G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are 3 risk factors for having a child with Down syndrome.</strong>
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Am. J. Med. Genet. 121A: 219-224, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20234" target="_blank">Full Text</a>]
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<a id="Chen1997" class="mim-anchor"></a>
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Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B.
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<strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong>
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J. Biol. Chem. 272: 3628, and 3634, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9013615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9013615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9013615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Christensen1999" class="mim-anchor"></a>
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Christensen, B., Arbour, L., Tran, P., Leclerc, D., Sabbaghian, N., Platt, R., Gilfix, B. M., Rosenblatt, D. S., Gravel, R. A., Forbes, P., Rozen, R.
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<strong>Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10323741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<151::aid-ajmg12>3.0.co;2-t" target="_blank">Full Text</a>]
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Doolin, M.-T., Barbaux, S., McDonnell, M., Hoess, K., Whitehead, A. S., Mitchell, L. E.
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<strong>Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.</strong>
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Am. J. Hum. Genet. 71: 1222-1226, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12375236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12375236</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12375236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/344209" target="_blank">Full Text</a>]
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<a id="Gulati1996" class="mim-anchor"></a>
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Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R.
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<strong>Defects in human methionine synthase in cblG patients.</strong>
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Hum. Molec. Genet. 5: 1859-1865, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/5.12.1859" target="_blank">Full Text</a>]
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Kvittingen, E. A., Spangen, S., Lindemans, J., Fowler, B.
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<strong>Methionine synthase deficiency without megaloblastic anaemia.</strong>
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Europ. J. Pediat. 156: 925-930, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9453374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9453374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9453374" 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/s004310050744" target="_blank">Full Text</a>]
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<a id="Leclerc1996" class="mim-anchor"></a>
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Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A.
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<strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Li1996" class="mim-anchor"></a>
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Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D.
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<strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong>
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Hum. Molec. Genet. 5: 1851-1858, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968735</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/5.12.1851" target="_blank">Full Text</a>]
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<a id="Mellman1979" class="mim-anchor"></a>
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Mellman, I. S., Lin, P.-F., Ruddle, F. H., Rosenberg, L. E.
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<strong>Genetic control of cobalamin binding in normal and mutant cells: assignment of the gene for 5-methyltetrahydrofolate: L-homocysteine S-methyltransferase to human chromosome 1.</strong>
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Proc. Nat. Acad. Sci. 76: 405-409, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/284356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">284356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=284356" 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.76.1.405" target="_blank">Full Text</a>]
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Mostowska2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mostowska, A., Hozyasz, K. K., Jagodzinski, P. P.
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<strong>Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population.</strong>
|
|
Clin. Genet. 69: 512-517, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00618.x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Mostowska2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mostowska, A., Hozyasz, K. K., Wojcicki, P., Dziegelewska, M., Jagodzinski, P. P.
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<strong>Associations of folate and choline metabolism gene polymorphisms with orofacial clefts.</strong>
|
|
J. Med. Genet. 47: 809-815, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19737740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19737740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19737740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2009.070029" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Paz2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Paz, M. F., Avila, S., Fraga, M. F., Pollan, M., Capella, G., Peinado, M. A., Sanchez-Cespedes, M., Herman, J. G., Esteller, M.
|
|
<strong>Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors.</strong>
|
|
Cancer Res. 62: 4519-4524, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12154064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12154064</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12154064" 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="13" class="mim-anchor"></a>
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<a id="Watkins1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watkins, D., Rosenblatt, D. S.
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<strong>Genetic heterogeneity among patients with methylcobalamin deficiency.</strong>
|
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J. Clin. Invest. 81: 1690-1694, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3384945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3384945</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3384945" 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/10.1172/JCI113507" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Watkins2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S.
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|
<strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong>
|
|
Am. J. Hum. Genet. 71: 143-153, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12068375[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=12068375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/341354" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Wildin1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wildin, R. S., Scott, C. R.
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<strong>Cbl-G: presentation, treatment, and prolonged followup in a patient with absence of methionine synthase. (Abstract)</strong>
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Am. J. Hum. Genet. 51: A357 only, 1992.
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</p>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Wilson1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A.
|
|
<strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong>
|
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Am. J. Hum. Genet. 63: 409-414, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/301976" target="_blank">Full Text</a>]
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Yamada2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamada, K., Gravel, R. A., Toraya, T., Matthews, R. G.
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<strong>Human methionine synthase reductase is a molecular chaperone for human methionine synthase.</strong>
|
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Proc. Nat. Acad. Sci. 103: 9476-9481, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16769880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16769880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16769880[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=16769880" 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.0603694103" target="_blank">Full Text</a>]
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Zhang2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Y., Zhang, M., Niu, T., Xu, X., Zhu, G., Huo, Y., Chen, C., Wang, X., Xing, H., Peng, S., Huang, A., Hong, X., Xu, X.
|
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<strong>D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.</strong>
|
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J. Hum. Genet. 49: 296-301, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148588</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15148588" 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/s10038-004-0149-0" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Zhang1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Z.-X., Leclerc, D., Gravel, R., Rozen, R.
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<strong>The methionine synthase (Mtr) gene maps to proximal mouse chromosome 13.</strong>
|
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Mammalian Genome 8: 787-797, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9321480" 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/s003359900570" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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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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</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 A. Bocchini - updated : 2/3/2011
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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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Patricia A. Hartz - updated : 7/19/2006<br>Cassandra L. Kniffin - updated : 7/10/2006<br>Victor A. McKusick - updated : 7/9/2004<br>Victor A. McKusick - updated : 10/7/2003<br>Victor A. McKusick - updated : 12/23/2002<br>Victor A. McKusick - updated : 10/8/2002<br>Victor A. McKusick - updated : 7/22/2002<br>Victor A. McKusick - updated : 5/10/1999<br>Victor A. McKusick - updated : 7/16/1998<br>Rebekah S. Rasooly - updated : 4/9/1998<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 10/14/1997<br>Moyra Smith - updated : 1/22/1997
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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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<a id="creationDate" class="mim-anchor"></a>
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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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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/2/1986
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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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 : 08/19/2015
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mcolton : 8/4/2015<br>carol : 10/3/2013<br>carol : 9/12/2013<br>carol : 7/12/2013<br>carol : 7/12/2013<br>carol : 7/11/2013<br>ckniffin : 7/11/2013<br>carol : 9/20/2011<br>carol : 2/3/2011<br>alopez : 10/29/2010<br>carol : 7/31/2006<br>carol : 7/31/2006<br>ckniffin : 7/26/2006<br>mgross : 7/20/2006<br>terry : 7/19/2006<br>wwang : 7/13/2006<br>ckniffin : 7/10/2006<br>alopez : 6/9/2006<br>terry : 4/18/2005<br>tkritzer : 7/14/2004<br>terry : 7/9/2004<br>alopez : 10/7/2003<br>alopez : 10/7/2003<br>alopez : 10/7/2003<br>alopez : 10/7/2003<br>tkritzer : 1/3/2003<br>tkritzer : 12/26/2002<br>terry : 12/23/2002<br>carol : 10/16/2002<br>tkritzer : 10/14/2002<br>terry : 10/8/2002<br>tkritzer : 7/30/2002<br>tkritzer : 7/29/2002<br>tkritzer : 7/29/2002<br>terry : 7/22/2002<br>ckniffin : 7/9/2002<br>cwells : 5/30/2001<br>carol : 5/18/1999<br>mgross : 5/13/1999<br>mgross : 5/13/1999<br>mgross : 5/12/1999<br>terry : 5/10/1999<br>dkim : 12/18/1998<br>terry : 8/21/1998<br>terry : 8/21/1998<br>terry : 8/5/1998<br>alopez : 7/17/1998<br>terry : 7/16/1998<br>alopez : 4/9/1998<br>alopez : 3/27/1998<br>terry : 3/26/1998<br>terry : 10/14/1997<br>alopez : 7/28/1997<br>terry : 7/8/1997<br>alopez : 6/2/1997<br>mark : 1/22/1997<br>terry : 1/22/1997<br>terry : 1/22/1997<br>mark : 1/22/1997<br>mimadm : 11/6/1994<br>warfield : 3/2/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>carol : 3/7/1990<br>ddp : 10/27/1989
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</span>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 156570
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE S-METHYLTRANSFERASE; MTR
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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TETRAHYDROPTEROYLGLUTAMATE METHYLTRANSFERASE<br />
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METHIONINE SYNTHASE; MS
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: MTR</em></strong>
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</span>
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</p>
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</div>
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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: 1q43
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:236,795,281-236,903,981 </span>
|
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</em>
|
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</strong>
|
|
<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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<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-Phenotype Relationships</strong>
|
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</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
1q43
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Neural tube defects, folate-sensitive, susceptibility to}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601634
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Homocystinuria-megaloblastic anemia, cblG complementation type
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
250940
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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|
|
<div>
|
|
<br />
|
|
</div>
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|
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|
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|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The remethylation of homocysteine to form methionine is catalyzed by the cytoplasmic enzyme 5-methyltetrahydrofolate-homocysteine S-methyltransferase (EC 2.1.1.13), which is also called methionine synthase. This enzyme requires methylcobalamin (MeCbl), a derivative of cobalamin, or vitamin B12, for activity (summary by Li et al., 1996). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Li et al. (1996) described the isolation and characterization of the human methionine synthase (MTR) cDNA. To isolate the MTR cDNA, they took advantage of the evolutionary conservation of MTR and identified sequence blocks of the homologous E. coli METH gene that showed high DNA homology with sequence blocks of MTR from C. elegans. They then designed primers for 4 regions of high DNA homology and used these to PCR amplify first strand cDNA from human lymphoblastoid cell lines. One of the primer pairs amplified a 350-bp fragment that on sequence analysis had 64% homology with the C. elegans protein. The 350-bp PCR fragment was used to isolate a clone from a hepatoma cDNA library. This clone extended from the middle of the predicted open reading frame (ORF) to a few hundred bp upstream of the predicted start codon. Additional clones were identified in the EST database by searching with the C-terminal ends of the C. elegans and the E. coli proteins. Li et al. (1996) reported that the human MTR gene encodes a protein of 1,265 amino acids. The MTR cDNA probes detected 7.5- and 10-kb transcripts in a range of different human tissues. The human probe hybridized to a single 5-kb message in mouse tissues. </p><p>Independently and simultaneously, Leclerc et al. (1996) sought to clone the human MTR gene by identifying 4 regions of homology among methionine synthases of 3 bacteria and C. elegans. They utilized sequence in these regions to design degenerate oligonucleotides to derive PCR products from reverse transcribed cDNA. These PCR products were then used to clone the human methionine synthase gene. Leclerc et al. (1996) reported that the methionine synthase gene encodes a 1,265-amino acid protein. They concluded that the cDNA that they had isolated represented methionine synthase on the basis of sequence homology and by identifying mutations in cblG patients with deficiency of enzyme activity. The most striking sequence homology was found in 4 boxes of 9 to 13 amino acids. Box 2 contains 13 consecutive residues which were identical in all known methionine synthases. Sequences in box 2 correspond to part of the cobalamin binding domain. </p><p>MTR cDNAs were isolated independently by Chen et al. (1997) using RT-PCR with primers based on conserved regions of E. coli and C. elegans methionine synthetase. In addition to the major 8- and 10-kb mRNAs, Chen et al. (1997) detected a minor 4.4-kb mRNA and other minor, partially spliced larger mRNAs on Northern blots. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Watkins et al. (2002) characterized the structure of the MTR gene, thereby identifying exon-intron boundaries and enabling amplification of each of the 33 exons of the gene from genomic DNA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In the studies of Mellman et al. (1979), when extracts prepared from cultured fibroblasts grown in medium containing cobalt-57-labeled cobalamin were analyzed by polyacrylamide gel, intracellular radioactivity was found to be associated with methionine synthase. For this reason and also because rodent and human forms of the enzyme were electrophoretically distinguishable, these workers could use binding to identify the presence of human methyltransferase (MTR) in rodent-human somatic cell hybrids. By this approach, they assigned the methyltransferase gene to chromosome 1. </p><p>Li et al. (1996) used the cDNA probes for chromosome mapping by in situ hybridization studies. They reported that the MTR gene maps to 1q42.3-1q44. Zhang et al. (1997) found that the mouse Mtr gene maps to proximal chromosome 13. </p><p>Leclerc et al. (1996) used cDNA probes and fluorescence in situ hybridization to assign the methionine synthase gene to chromosome 1q43. </p><p>Chen et al. (1997) confirmed the map position of the MTR gene to 1q42.3-q43 by fluorescence in situ hybridization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using purified recombinant human proteins, Yamada et al. (2006) found that MTRR maintained MTR activity at a 1:1 stoichiometric ratio. In the presence of MTRR and NADPH, holoenzyme formation from apoMTR and methylcobalamin was significantly enhanced due to stabilization of apoMTR in the presence of MTRR. MTRR was also able to reduce aquacobalamin to cob(II)alamin in the presence of NADPH, which stimulated conversion of apoMTR and aquacobalamin to holoMTR. Yamada et al. (2006) concluded that MTRR serves as a chaperone for MTR and as an aquacobalamin reductase, rather than acting solely in reductive activation of MTR. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Homocystinuria-Megaloblastic Anemia, cblG Complementation Type</em></strong></p><p>
|
|
Li et al. (1996) reviewed the role of MTR in homocysteine metabolism. They noted that loss-of-function mutations in MTR would cause increased levels of plasma homocysteine. They noted also that defects in MTR activity may play a role in tumorigenesis, since approximately 50% of tumor cells require the addition of exogenous methionine for growth and homocysteine and folate cannot replace methionine. Li et al. (1996) concluded that since methionine can only be synthesized by methylation of homocysteine, the inability of tumor cells to grow on homocysteine suggests that they have a defect in methionine synthase. With that in mind, Gulati et al. (1996) analyzed the molecular basis for methionine synthase deficiency in cell lines derived from 2 patients with cblG disorder (HMAG; 250940). The 79/76 cell line (from a patient with severe neurologic dysfunction and homocystinuria but no megaloblastic anemia) had low levels of MTR activity and a diminished level of MTR mRNA. In the WG1892 cell line (from a patient with mental retardation, macrocytic anemia, and homocystinuria), they detected a pro1173-to-leu mutation (156570.0001) and a 3-bp deletion leading to loss of ile881 (156570.0002). Gulati et al. (1996) stated that the onset of symptoms was within the first 4 months of life for each patient. </p><p>Leclerc et al. (1996) identified 2 mutations (156570.0002, 156570.0003) in the vicinity of the cobalamin-binding domain in cell lines derived from patients with cblG disease, one of whom (WG1892) was also reported by Gulati et al. (1996). </p><p>In a panel of 21 patients with methylcobalamin deficiency G (cblG) disorder, Watkins et al. (2002) identified 13 novel mutations. These included 5 deletions and 2 nonsense mutations that resulted in synthesis of truncated proteins that lacked portions critical for enzyme function. In addition, a previously described missense mutation, P1173L (156570.0001), was detected in 16 patients in an expanded panel of 24 patients with cblG. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C-to-T transition in a CpG island, has occurred on at least 2 separate genetic backgrounds. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
Evaluation of the relationship between variation in genes that are involved in the folate-homocysteine metabolic axis and the risk of neural tube defects (601634) is complicated by the potential involvement of both the maternal and embryonic genotypes in determination of disease risk. Doolin et al. (2002) designed a study to address questions regarding both maternal and embryonic genetic risk factors for spina bifida by use of the 2-step transmission/disequilibrium test. Analysis of data on variants of 2 genes involved in homocysteine remethylation/methionine biosynthesis, viz., the MTR 2756A-G (156570.0008) and methionine synthase reductase (MTRR, or MSR; 602568) 66A-G (602568.0003) polymorphisms, provided evidence that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype. For both variants, the risk of having a child with spina bifida appeared to increase with the number of high-risk alleles in the maternal genotype. The findings highlighted the importance of considering both the maternal and embryonic genotypes when evaluating putative spina bifida susceptibility loci. </p><p>Zhang et al. (2004) studied 726 Chinese patients with hypertension (145500) and their families for the association between the asp919-to-glu (D919G) polymorphism of the MTR gene and the antihypertensive effect of the angiotensin-converting enzyme (ACE; 106180) inhibitor benazepril. Compared to the 919D allele, both population-based and family-based association tests demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. </p><p>Mostowska et al. (2006) found increased frequency of the 2756G allele among 122 Polish mothers of children with orofacial clefts (see 119530). Mothers with the GA or GG genotypes had an odds ratio of 2.195 for having a child with cleft lip/palate compared to mothers with the AA genotype. In another study of 174 Polish children with cleft lip/palate or cleft lip only, Mostowska et al. (2010) found no association with SNPs in the MTR gene. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, PRO1173LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913578,
|
|
|
|
|
|
gnomAD: rs121913578,
|
|
|
|
|
|
ClinVar: RCV000015348, RCV000162189, RCV000210576, RCV000414734, RCV000778974, RCV001003947
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line (WG1892) from a CblG (HMAG; 250940) patient with mental retardation, macrocytic anemia, and homocystinuria, Gulati et al. (1996) detected compound heterozygous mutations in the MTR gene: a 3804C-T transition resulting in a pro1173-to-leu (P1173L) amino acid substitution, and a 3-bp deletion (2926del3; 156570.0002). </p><p>In a panel of 24 patients with the cblG disorder, Watkins et al. (2002) found the P1173L mutation in 16 patients. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C-to-T transition in the CpG island, has occurred on at least 2 separate genetic backgrounds. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, 3-BP DEL, NT2926
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044443,
|
|
|
|
|
|
|
|
ClinVar: RCV000015349, RCV002482871
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 3-bp deletion in the MTR gene (2926del3) that was found in compound heterozygous state in a cell line (WG1892) from a CblG (HMAG; 250940) patient by Gulati et al. (1996), see 156570.0001. </p><p>Leclerc et al. (1996) also reported this mutation in the WG1892 cell line. They stated that the patient was a Caucasian male who was diagnosed at age 4 years with developmental delay, tremors, gait instability, megaloblastic anemia, and homocystinuria. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, HIS920ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913579,
|
|
|
|
|
|
gnomAD: rs121913579,
|
|
|
|
|
|
ClinVar: RCV000015350
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Leclerc et al. (1996) identified a 2758C-G point mutation in heterozygous form in the MTR gene of cblG (250940) patient cell line WG2290. It resulted in a his920-to-asp (H920D) substitution and loss of a Sau96I restriction site. The second mutation in this cell line was not identified. This cell line was derived from a Caucasian male who presented at 3 months of age with failure to thrive, severe eczema, megaloblastic anemia, homocystinuria, and methylmalonic aciduria. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, IVS3AS, A-G, -166
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1661117141,
|
|
|
|
|
|
|
|
ClinVar: RCV000015351
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with the cblG variant form of methionine synthase deficiency (250940), Wilson et al. (1998) identified compound heterozygosity for 2 null mutations in the MTR gene: an A-to-G substitution at position -166 of intron 3, resulting in a 165-bp insertion and premature termination, and a 2-bp deletion (2112delTC; 156570.0005), resulting in a frameshift and premature termination. The patients had a severe disorder with early onset and psychomotor retardation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, 2-BP DEL, 2112TC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044444,
|
|
|
|
|
|
|
|
ClinVar: RCV000015352
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 2-bp deletion in the MTR gene (2112delTC) that was found in compound heterozygous state in a brother and sister with the cblG variant form of methionine synthase deficiency (250940) by Wilson et al. (1998), see 156570.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTR, IVS6AS, G-A, LYS203
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000015353
|
|
|
|
|
|
</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 a boy with the cblG variant form of methionine synthase deficiency (250940), Wilson et al. (1998) found compound heterozygosity for 2 null mutations of the MTR gene. One was a 1-bp insertion, 3378insA (156570.0007), which resulted in a frameshift and a downstream stop codon. The other was a splice site mutation which resulted in 2 different insertions in the mRNA: 1 of 78 bp and another of 128 bp, beginning after lys203. The 78-bp insertion was found to be a truncated version of the 128-bp insertion, missing the last 50 bp. By means of genomic sequencing, the insertions were discovered to be the result of a G-to-A substitution near the center of the intron after exon 6 that created a single cryptic 3-prime acceptor splice site. For each insert, a cryptic 5-prime donor splice site was recruited to complete the new exon, 1 at 78 bp and the other at 128 bp downstream of the mutation. Neither of the newly created 5-prime donor sites was preferred since the 2 transcripts appeared to occur in equal amounts. An in-frame stop codon occurred 9 bp into the insertions. The patient presented with short stature, failure to thrive, progressive weakness, hypotonia, ocular nystagmus, jaundice, feeding difficulties, and diarrhea at 7 to 10 weeks of age (Wildin and Scott, 1992). He had severe megaloblastic anemia and neutropenia, homocysteinemia, hypomethioninemia, and formiminoglutamic aciduria without methylmalonic aciduria, which led to the diagnosis of a defect in methionine synthesis. Treatment resulted in improved metabolite levels, improvement of tone, and reduction of nystagmus, but poor growth, developmental delay, feeding difficulties requiring a gastrostomy, persistent anemia, and immunologic deficits were present at age 4 years. </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-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</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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MTR, 1-BP INS, 3378A
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<br />
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SNP: rs797044445,
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ClinVar: RCV000015354
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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 1-bp insertion in the MTR gene (3378insA) that was found in compound heterozygous state in a patient with the cblG variant form of methionine synthase deficiency (250940) by Wilson et al. (1998), see 156570.0006. </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>.0008 NEURAL TUBE DEFECTS, FOLATE-SENSITIVE, SUSCEPTIBILITY TO</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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MTR, 2756A-G
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<br />
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SNP: rs1805087,
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gnomAD: rs1805087,
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ClinVar: RCV000015355, RCV000126868, RCV000144923, RCV000398009, RCV001519615, RCV001812069, RCV003982899
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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>Leclerc et al. (1996) and Chen et al. (1997) identified a common 2756A-G polymorphism of the MTR gene, resulting in the conversion of an aspartic acid residue to a glycine residue. Christensen et al. (1999) studied this polymorphism and the 677C-T polymorphism of the MTHFR gene (607093.0003) in 56 patients with spina bifida (see 601634), 62 mothers of the patients, 97 children without neural tube defects (controls), and 90 mothers of controls. The 2756G allele was associated with a decreased odds ratio; none of the cases and only 10% of controls were homozygous for this variant. </p><p>Aberrant DNA methylation is a common feature of human neoplasia. Paz et al. (2002) studied interindividual inherited susceptibility to the epigenetic processes of CpG island hypermethylation and global genomic hypomethylation, which are observed simultaneously in cancer cells. They genotyped 233 patients with colorectal, breast, or lung tumors for 4 germline variants in 3 key genes involved in the metabolism of the methyl group. A positive association of aberrant methylation was found with homozygosity for the MTR 2756G allele as well as with the 677T allele of the MTHFR gene. </p><p>Doolin et al. (2002) analyzed data on this polymorphism and the A66G polymorphism of the methionine synthase reductase gene (602568.0003) and concluded that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype. For both variants, the risk of having a child with spina bifida appeared to increase with the number of high-risk alleles in the maternal genotype. </p><p>Bosco et al. (2003) studied the influence of the polymorphisms MTHFR 677C-T (607093.0003) and 1298A-C (607093.0004), MTR 2756A-G, and MTRR 66A-G (602568.0003) on the risk of being a Down syndrome (DS; 190685) case or having a DS child (case mother). Plasma homocysteine and other factors were likewise studied. They found that after adjustment for age, total homocysteine and MTR 2756 AG/GG genotype were significant risk factors for having a DS child, with odds ratio (OR) of 6.7 and 3.5, respectively. The MTR 2756 AG/GG genotype increased significantly the risk of being a DS case, with an OR of 3.8. Double heterozygosity for MTR 2756 AG/MTRR 66 AG was the single combined genotype that was a significant risk factor for having a DS child, with an OR estimated at 5.0, after adjustment for total homocysteine level. </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>.0009 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</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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MTR, ARG585TER
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<br />
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SNP: rs121913580,
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gnomAD: rs121913580,
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ClinVar: RCV000015356, RCV005016268
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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 a cell line (WG1975) from a patient with cblG disease (250940), Watkins et al. (2002) identified a 1753C-T transition in the MTR gene, resulting in an arg585-to-ter (R585X) substitution. The mutation was predicted to result in synthesis of a truncated protein that lacked portions critical for enzyme function. </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>.0010 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</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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MTR, GLU1204TER
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<br />
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SNP: rs121913581,
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ClinVar: RCV000015357
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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 a cell line (WG2292) from a patient with cblG disease (250940), Watkins et al. (2002) identified a 3613G-T transversion in the MTR gene, resulting in a glu1204-to-ter (E1204X) substitution. The mutation was predicted to result in synthesis of a truncated protein that lacked portions critical for enzyme function. </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>.0011 HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE</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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MTR, ALA410PRO
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<br />
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SNP: rs121913582,
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gnomAD: rs121913582,
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|
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ClinVar: RCV000015358, RCV004525853, RCV005007853
|
|
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a cell line (WG2009) from a patient with cblG disease (250940), Watkins et al. (2002) identified a 1228G-C transversion in the MTR gene, resulting in an ala410-to-pro (A410P) 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>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Kvittingen et al. (1997); Watkins and Rosenblatt (1988)
|
|
</span>
|
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<div>
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<br />
|
|
</div>
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Bosco, P., Gueant-Rodriguez, R. M., Anello, G., Barone, C., Namour, F., Caraci, F., Romano, A., Romano, C., Gueant, J. L.
|
|
<strong>Methionine synthase (MTR) 2756 (A-G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are 3 risk factors for having a child with Down syndrome.</strong>
|
|
Am. J. Med. Genet. 121A: 219-224, 2003.
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[PubMed: 12923861]
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[Full Text: https://doi.org/10.1002/ajmg.a.20234]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chen, L. H., Liu, M.-L., Hwang, H.-Y., Chen, L.-S., Korenberg, J., Shane, B.
|
|
<strong>Human methionine synthase: cDNA cloning, gene localization, and expression.</strong>
|
|
J. Biol. Chem. 272: 3628, and 3634, 1997.
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[PubMed: 9013615]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Christensen, B., Arbour, L., Tran, P., Leclerc, D., Sabbaghian, N., Platt, R., Gilfix, B. M., Rosenblatt, D. S., Gravel, R. A., Forbes, P., Rozen, R.
|
|
<strong>Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects.</strong>
|
|
Am. J. Med. Genet. 84: 151-157, 1999.
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[PubMed: 10323741]
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[Full Text: https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<151::aid-ajmg12>3.0.co;2-t]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Doolin, M.-T., Barbaux, S., McDonnell, M., Hoess, K., Whitehead, A. S., Mitchell, L. E.
|
|
<strong>Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.</strong>
|
|
Am. J. Hum. Genet. 71: 1222-1226, 2002.
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[PubMed: 12375236]
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[Full Text: https://doi.org/10.1086/344209]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gulati, S., Baker, P., Li, Y. N., Fowler, B., Kruger, W., Brody, L. C., Banerjee, R.
|
|
<strong>Defects in human methionine synthase in cblG patients.</strong>
|
|
Hum. Molec. Genet. 5: 1859-1865, 1996.
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[PubMed: 8968736]
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[Full Text: https://doi.org/10.1093/hmg/5.12.1859]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Kvittingen, E. A., Spangen, S., Lindemans, J., Fowler, B.
|
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<strong>Methionine synthase deficiency without megaloblastic anaemia.</strong>
|
|
Europ. J. Pediat. 156: 925-930, 1997.
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[PubMed: 9453374]
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[Full Text: https://doi.org/10.1007/s004310050744]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., Eydoux, P., Rosenblatt, D. S., Rozen, R., Gravel, R. A.
|
|
<strong>Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.</strong>
|
|
Hum. Molec. Genet. 5: 1867-1874, 1996.
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|
[PubMed: 8968737]
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[Full Text: https://doi.org/10.1093/hmg/5.12.1867]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Li, Y. N., Gulati, S., Baker, P. J., Brody, L. C., Banerjee, R., Kruger, W. D.
|
|
<strong>Cloning, mapping and RNA analysis of the human methionine synthase gene.</strong>
|
|
Hum. Molec. Genet. 5: 1851-1858, 1996.
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[PubMed: 8968735]
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[Full Text: https://doi.org/10.1093/hmg/5.12.1851]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Mellman, I. S., Lin, P.-F., Ruddle, F. H., Rosenberg, L. E.
|
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<strong>Genetic control of cobalamin binding in normal and mutant cells: assignment of the gene for 5-methyltetrahydrofolate: L-homocysteine S-methyltransferase to human chromosome 1.</strong>
|
|
Proc. Nat. Acad. Sci. 76: 405-409, 1979.
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[PubMed: 284356]
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[Full Text: https://doi.org/10.1073/pnas.76.1.405]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Mostowska, A., Hozyasz, K. K., Jagodzinski, P. P.
|
|
<strong>Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population.</strong>
|
|
Clin. Genet. 69: 512-517, 2006.
|
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|
|
[PubMed: 16712703]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00618.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mostowska, A., Hozyasz, K. K., Wojcicki, P., Dziegelewska, M., Jagodzinski, P. P.
|
|
<strong>Associations of folate and choline metabolism gene polymorphisms with orofacial clefts.</strong>
|
|
J. Med. Genet. 47: 809-815, 2010.
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|
|
[PubMed: 19737740]
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[Full Text: https://doi.org/10.1136/jmg.2009.070029]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Paz, M. F., Avila, S., Fraga, M. F., Pollan, M., Capella, G., Peinado, M. A., Sanchez-Cespedes, M., Herman, J. G., Esteller, M.
|
|
<strong>Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors.</strong>
|
|
Cancer Res. 62: 4519-4524, 2002.
|
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|
|
[PubMed: 12154064]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Watkins, D., Rosenblatt, D. S.
|
|
<strong>Genetic heterogeneity among patients with methylcobalamin deficiency.</strong>
|
|
J. Clin. Invest. 81: 1690-1694, 1988.
|
|
|
|
|
|
[PubMed: 3384945]
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|
[Full Text: https://doi.org/10.1172/JCI113507]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Watkins, D., Ru, M., Hwang, H.-Y., Kim, C. D., Murray, A., Philip, N. S., Kim, W., Legakis, H., Wai, T., Hilton, J. F., Ge, B., Dore, C., Hosack, A., Wilson, A., Gravel, R. A., Shane, B., Hudson, T. J., Rosenblatt, D. S.
|
|
<strong>Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.</strong>
|
|
Am. J. Hum. Genet. 71: 143-153, 2002.
|
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|
|
[PubMed: 12068375]
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|
[Full Text: https://doi.org/10.1086/341354]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Wildin, R. S., Scott, C. R.
|
|
<strong>Cbl-G: presentation, treatment, and prolonged followup in a patient with absence of methionine synthase. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51: A357 only, 1992.
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Wilson, A., Leclerc, D., Saberi, F., Campeau, E., Hwang, H. Y., Shane, B., Phillips, J. A., III, Rosenblatt, D. S., Gravel, R. A.
|
|
<strong>Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.</strong>
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Am. J. Hum. Genet. 63: 409-414, 1998.
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[PubMed: 9683607]
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[Full Text: https://doi.org/10.1086/301976]
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Yamada, K., Gravel, R. A., Toraya, T., Matthews, R. G.
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<strong>Human methionine synthase reductase is a molecular chaperone for human methionine synthase.</strong>
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Proc. Nat. Acad. Sci. 103: 9476-9481, 2006.
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[PubMed: 16769880]
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[Full Text: https://doi.org/10.1073/pnas.0603694103]
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Zhang, Y., Zhang, M., Niu, T., Xu, X., Zhu, G., Huo, Y., Chen, C., Wang, X., Xing, H., Peng, S., Huang, A., Hong, X., Xu, X.
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<strong>D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.</strong>
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J. Hum. Genet. 49: 296-301, 2004.
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[PubMed: 15148588]
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[Full Text: https://doi.org/10.1007/s10038-004-0149-0]
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Zhang, Z.-X., Leclerc, D., Gravel, R., Rozen, R.
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<strong>The methionine synthase (Mtr) gene maps to proximal mouse chromosome 13.</strong>
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Mammalian Genome 8: 787-797, 1997.
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[PubMed: 9321480]
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[Full Text: https://doi.org/10.1007/s003359900570]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Carol A. Bocchini - updated : 2/3/2011<br>Patricia A. Hartz - updated : 7/19/2006<br>Cassandra L. Kniffin - updated : 7/10/2006<br>Victor A. McKusick - updated : 7/9/2004<br>Victor A. McKusick - updated : 10/7/2003<br>Victor A. McKusick - updated : 12/23/2002<br>Victor A. McKusick - updated : 10/8/2002<br>Victor A. McKusick - updated : 7/22/2002<br>Victor A. McKusick - updated : 5/10/1999<br>Victor A. McKusick - updated : 7/16/1998<br>Rebekah S. Rasooly - updated : 4/9/1998<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 10/14/1997<br>Moyra Smith - updated : 1/22/1997
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Victor A. McKusick : 6/2/1986
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