3903 lines
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Entry
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- *602360 - L-ARGININE:GLYCINE AMIDINOTRANSFERASE; GATM
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- OMIM
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<p>
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<span class="h4">*602360</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/602360">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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=ENSG00000171766;t=ENST00000396659" 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=2628" 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=602360" 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 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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</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=ENSG00000171766;t=ENST00000396659" 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_001321015,NM_001482,XM_047432385,XM_047432386,XM_047432387,XM_047432388" 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_001482" 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=602360" 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=03838&isoform_id=03838_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/GATM" 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/545385,1730201,4503933,13278726,62898902,119597712,119597713,119597714,194379018,194390954,332367931,1005261216,2217300775,2217300777,2217300779,2217300781,2462543649,2462543651,2462543653,2462543655,2462543657" 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/P50440" 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=2628" 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=ENSG00000171766;t=ENST00000396659" 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=GATM" 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=GATM" 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+2628" 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/GATM" 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:2628" 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/2628" 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=chr15&hgg_gene=ENST00000396659.8&hgg_start=45361124&hgg_end=45402227&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/genes/HGNC:4175" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/gatm" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602360[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602360[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/GATM/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/ENSG00000171766" 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=GATM" 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=GATM" 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=GATM" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/GATM" 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=GATM&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/PA28590" 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:4175" 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:1914342" 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/GATM#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:1914342" 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/2628/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=2628" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-021015-1" 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">
|
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<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:602360" 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">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2628" 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=GATM&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 702440000<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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602360
|
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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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L-ARGININE:GLYCINE AMIDINOTRANSFERASE; GATM
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
AGAT
|
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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>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GATM" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GATM</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/15/180?start=-3&limit=10&highlight=180">15q21.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:45361124-45402227&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'})">15:45,361,124-45,402,227</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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</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=612718,134600" 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/15/180?start=-3&limit=10&highlight=180">
|
|
15q21.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cerebral creatine deficiency syndrome 3
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/612718"> 612718 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
|
</td>
|
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</tr>
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<tr>
|
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<td>
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<p>Creatine and phosphocreatine play important roles in the energy metabolism of muscle and nerve tissues. The enzyme L-arginine:glycine amidinotransferase (GATM; <a href="https://enzyme.expasy.org/EC/2.1.4.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.1.4.1</a>) catalyzes the transfer of a guanido group from arginine to glycine, forming guanidinoacetic acid, the immediate precursor of creatine. The major sites of creatine biosynthesis are pancreas, kidney, and liver, where GATM appears to be located in mitochondria of cells (summary by <a href="#8" class="mim-tip-reference" title="Humm, A., Huber, R., Mann, K. <strong>The amino acid sequences of human and pig L-arginine:glycine amidinotransferase.</strong> FEBS Lett. 339: 101-107, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8313955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8313955</a>] [<a href="https://doi.org/10.1016/0014-5793(94)80394-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8313955">Humm et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8313955" 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="Humm, A., Huber, R., Mann, K. <strong>The amino acid sequences of human and pig L-arginine:glycine amidinotransferase.</strong> FEBS Lett. 339: 101-107, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8313955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8313955</a>] [<a href="https://doi.org/10.1016/0014-5793(94)80394-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8313955">Humm et al. (1994)</a> isolated and sequenced Gatm, which they called Agat, from pig kidney mitochondria. Sequence data from the pig Agat polypeptide allowed them to isolate cDNA clones encoding the human enzyme from a kidney carcinoma cDNA library. The largest human cDNA sequence encodes a 423-amino acid polypeptide including a 37-amino acid signal sequence. The mature porcine and human proteins are 94% identical to each other and 36% identical to bacterial L-arginine:inosamine phosphate amidinotransferase. <a href="#7" class="mim-tip-reference" title="Humm, A., Fritsche, E., Mann, K., Gohl, M., Huber, R. <strong>Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue.</strong> Biochem. J. 322: 771-776, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9148748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9148748</a>] [<a href="https://doi.org/10.1042/bj3220771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9148748">Humm et al. (1997)</a> noted that mitochondrial and cytosolic forms of AGAT are believed to derive from the same gene by alternative splicing. They expressed human AGAT in E. coli and identified its active-site cysteine residue (cys407). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8313955+9148748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G. <strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong> Am. J. Hum. Genet. 69: 1127-1133, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11555793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11555793</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11555793[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/10.1086/323765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11555793">Item et al. (2001)</a> stated that the GATM genomic DNA is 16,858 bp long and contains 9 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11555793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G. <strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong> Am. J. Hum. Genet. 69: 1127-1133, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11555793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11555793</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11555793[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/10.1086/323765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11555793">Item et al. (2001)</a> stated that the human GATM gene is located on chromosome 15q15.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11555793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 4/14/2016."None>Gross (2016)</a> mapped the GATM gene to chromosome 15q21.1 based on an alignment of the GATM sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC004141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC004141</a>) with the genomic sequence (GRCh38).</p>
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<p><strong><em>Cerebral Creatine Deficiency Syndrome 3</em></strong></p><p>
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In 2 sisters with cerebral creatine deficiency syndrome-3 (CCDS3; <a href="/entry/612718">612718</a>) reported by <a href="#2" class="mim-tip-reference" title="Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R. <strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong> Ann. Neurol. 47: 511-513, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762163</a>]" pmid="10762163">Bianchi et al. (2000)</a>, <a href="#9" class="mim-tip-reference" title="Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G. <strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong> Am. J. Hum. Genet. 69: 1127-1133, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11555793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11555793</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11555793[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/10.1086/323765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11555793">Item et al. (2001)</a> identified a homozygous trp149-to-ter mutation in the GATM gene (W149X; <a href="#0001">602360.0001</a>), resulting in undetectable cDNA, as investigated by RT-PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. In an affected male cousin of the sibs reported by <a href="#2" class="mim-tip-reference" title="Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R. <strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong> Ann. Neurol. 47: 511-513, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762163</a>]" pmid="10762163">Bianchi et al. (2000)</a>, <a href="#1" class="mim-tip-reference" title="Battini, R., Leuzzi, V., Carducci, C., Tosetti, M., Bianchi, M. C., Item, C. B., Stockler-Ipsiroglu, S., Cioni, G. <strong>Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree.</strong> Molec. Genet. Metab. 77: 326-331, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12468279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12468279</a>] [<a href="https://doi.org/10.1016/s1096-7192(02)00175-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12468279">Battini et al. (2002)</a> identified homozygosity for the same W149X mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11555793+12468279+10762163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born of unrelated Yemenite Jewish parents, with cerebral creatine deficiency syndrome-3, <a href="#5" class="mim-tip-reference" title="Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M., Katz-Brull, R. <strong>L-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.</strong> Molec. Genet. Metab. 101: 228-232, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20682460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20682460</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.06.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20682460">Edvardson et al. (2010)</a> identified a homozygous truncating mutation in the GATM gene (<a href="#0002">602360.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20682460" 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>Fanconi Renotubular Syndrome 1</em></strong></p><p>
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In 28 affected members from 5 unrelated families with Fanconi renotubular syndrome-1 (FRTS1; <a href="/entry/134600">134600</a>), <a href="#13" class="mim-tip-reference" title="Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others. <strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong> J. Am. Soc. Nephrol. 29: 1849-1858, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>] [<a href="https://doi.org/10.1681/ASN.2017111179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29654216">Reichold et al. (2018)</a> identified 4 different heterozygous missense mutations in the GATM gene (P320S, <a href="#0006">602360.0006</a>; T336A, <a href="#0007">602360.0007</a>; T336I, <a href="#0008">602360.0008</a>; and P34L, <a href="#0009">602360.0009</a>). The mutations, which were found by a combination of linkage analysis and candidate gene sequencing, next-generation gene sequencing, and exome sequencing, were confirmed by Sanger sequencing; the variants segregated with the disorder in all families. In silico modeling suggested that the mutations may adversely affect protein folding and possibly predispose the mutant protein to aggregation. Overexpression of the mutations in renal proximal tubule cells resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. Cells transfected with the T336A mutation showed decreased mitochondrial turnover rate, increased reactive oxygen species (ROS), activation of the inflammasome, including elevated IL18 (<a href="/entry/600953">600953</a>), increased levels of fibronectin and actin mRNA, and increased cell death compared to controls. These findings provided a mechanistic link between kidney fibrosis and progressive renal failure observed in the patients. Examination of Gatm-null mice showed no evidence of aminoaciduria or glycosuria, consistent with no effect on renal proximal tubular function. However, treatment of rats with oral creatine reduced renal Gatm expression and protein levels, suggesting that it could be a possible intervention to suppress the endogenous production of mutant GATM and dampen the formation of deleterious mitochondrial deposits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" 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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<a href="#10" class="mim-tip-reference" title="Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., Feng, Q., Rieder, M. J., and 11 others. <strong>A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.</strong> Nature 502: 377-380, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23995691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23995691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23995691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23995691">Mangravite et al. (2013)</a> identified a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment. This analysis identified 6 expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs9806699;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs9806699</a>, a cis-eQTL for the GATM gene, which encodes the rate-limiting enzyme in creatine synthesis. <a href="#10" class="mim-tip-reference" title="Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., Feng, Q., Rieder, M. J., and 11 others. <strong>A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.</strong> Nature 502: 377-380, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23995691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23995691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23995691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23995691">Mangravite et al. (2013)</a> found this locus to be associated with incidence of statin-induced myotoxicity in 2 separate populations (metaanalysis odds ratio = 0.60). Furthermore, <a href="#10" class="mim-tip-reference" title="Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., Feng, Q., Rieder, M. J., and 11 others. <strong>A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.</strong> Nature 502: 377-380, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23995691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23995691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23995691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23995691">Mangravite et al. (2013)</a> found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23995691" 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="Sandell, L. L., Guan, X.-J., Ingram, R., Tilghman, S. M. <strong>Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta.</strong> Proc. Nat. Acad. Sci. 100: 4622-4627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12671064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12671064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12671064[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.0230424100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12671064">Sandell et al. (2003)</a> demonstrated in the mouse that Gatm, which is expressed during development, is imprinted in the placenta and yolk sac, but not in embryonic tissues. The Gatm gene maps to mouse chromosome 2 in a region that had not previously been shown to contain imprinted genes. To determine whether Gatm is located in a cluster of imprinted genes, <a href="#14" class="mim-tip-reference" title="Sandell, L. L., Guan, X.-J., Ingram, R., Tilghman, S. M. <strong>Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta.</strong> Proc. Nat. Acad. Sci. 100: 4622-4627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12671064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12671064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12671064[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.0230424100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12671064">Sandell et al. (2003)</a> investigated the expression pattern of genes located near Gatm: Duox1 (<a href="/entry/606758">606758</a>), Duox2 (<a href="/entry/606759">606759</a>), Slc28a2 (<a href="/entry/606208">606208</a>), Slc30a4 (<a href="/entry/602095">602095</a>), and a transcript corresponding to LOC214616 and found no evidence that any is imprinted in placenta. These data were the first to link creatine metabolism with imprinting and the parental 'tug-of-war' for energy resources during development. Although many imprinted genes are associated with differentially methylated CpG islands, the Gatm gene resides in apparent isolation from other imprinted genes and is associated with an unmethylated CpG island. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12671064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Choe, C., Nabuurs, C., Stockebrand, M. C., Neu, A., Nunes, P., Morellini, F., Sauter, K., Schillemeit, S., Hermans-Borgmeyer, I., Marescau, B., Heerschap, A., Isbrandt, D. <strong>L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.</strong> Hum. Molec. Genet. 22: 110-123, 2013. Note: Erratum: Hum. Molec. Genet.: 22: 4030 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23026748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23026748</a>] [<a href="https://doi.org/10.1093/hmg/dds407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23026748">Choe et al. (2013)</a> found that Gatm -/- mice were born at the expected mendelian ratio. Gatm -/- mice did not require special treatment for survival, but they showed multiple abnormalities, and both sexes were infertile. Gatm -/- mice were lean and short with markedly reduced body mass index, accompanied by low serum leptin (LEP; <a href="/entry/164160">164160</a>) levels and the expected creatine deficiency. Gatm -/- mice showed increased food intake compared with controls. They also showed reduced locomotor activity, reduced body tension, and severe scoliosis, indicating chronic muscular hypotonia. 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<p>In 2 sisters with cerebral creatine deficiency syndrome-3 (CCDS3; <a href="/entry/612718">612718</a>) reported by <a href="#2" class="mim-tip-reference" title="Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R. <strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong> Ann. Neurol. 47: 511-513, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762163</a>]" pmid="10762163">Bianchi et al. (2000)</a>, <a href="#9" class="mim-tip-reference" title="Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G. <strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong> Am. J. Hum. Genet. 69: 1127-1133, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11555793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11555793</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11555793[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/10.1086/323765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11555793">Item et al. (2001)</a> identified a homozygous 9297G-A transition, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (W149X) of the GATM gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11555793+10762163" 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 an affected cousin of the sibs reported by <a href="#2" class="mim-tip-reference" title="Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R. <strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong> Ann. Neurol. 47: 511-513, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762163</a>]" pmid="10762163">Bianchi et al. (2000)</a>, <a href="#1" class="mim-tip-reference" title="Battini, R., Leuzzi, V., Carducci, C., Tosetti, M., Bianchi, M. C., Item, C. B., Stockler-Ipsiroglu, S., Cioni, G. <strong>Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree.</strong> Molec. Genet. Metab. 77: 326-331, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12468279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12468279</a>] [<a href="https://doi.org/10.1016/s1096-7192(02)00175-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12468279">Battini et al. (2002)</a> identified homozygosity for the same W149X mutation; his parents and 10 additional subjects in the pedigree were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12468279+10762163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sibs, born of unrelated Yemenite Jewish parents, with cerebral creatine deficiency syndrome-3 (CCDS3; <a href="/entry/612718">612718</a>), <a href="#5" class="mim-tip-reference" title="Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M., Katz-Brull, R. <strong>L-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.</strong> Molec. Genet. Metab. 101: 228-232, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20682460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20682460</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.06.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20682460">Edvardson et al. (2010)</a> identified a homozygous 1-bp insertion (1111insA) in the GATM gene, resulting in a frameshift and premature termination at codon 376. Each unaffected parent was heterozygous for the mutation, which was not found in 57 ethnic controls. Both patients showed delayed psychomotor development in infancy with poor speech acquisition. Each also had symptoms of a myopathy, with easy fatigability and predominantly proximal muscle weakness and atrophy. Brain MRS showed decreased creatine, and urine guanidinoacetate levels were low. Treatment with oral creatine resulted in clinical improvement and increased cerebral creatine levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20682460" 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>.0003 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397514708 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514708;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/rs397514708?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=rs397514708" 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=rs397514708" 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=RCV000049332 OR RCV002490622" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049332, RCV002490622" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049332...</a>
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<p>In 2 Jordanian sibs, born of consanguineous parents, with cerebral creatine deficiency syndrome 3 (CCDS3; <a href="/entry/612718">612718</a>), <a href="#15" class="mim-tip-reference" title="Verma, A. <strong>Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy.</strong> Neurology 75: 186-188, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20625172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20625172</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181e7cabd" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20625172">Verma (2010)</a> identified a homozygous arg169-to-ter (R169X) substitution in the GATM gene. Both patients showed delayed development in early childhood and began to show progressive proximal muscle weakness with features of a myopathy in their late teens. Laboratory studies showed undetectable GAA levels. Treatment with oral creatine supplementation resulted in dramatic improvement of muscle strength, but speech and cognitive impairment were unchanged. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20625172" 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="Comeaux, M. S., Wang, J., Wang, G., Kleppe, S., Zhang, V. W., Schmitt, E. S., Craigen, W. J., Renaud, D., Sun, Q., Wong, L.-J. <strong>Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.</strong> Molec. Genet. Metab. 109: 260-268, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23660394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23660394</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23660394">Comeaux et al. (2013)</a> reported 2 sibs with CCDSD3 who were homozygous for a c.505C-T transition in exon 4 of the GATM gene, resulting in an R169X substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23660394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0004 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</strong>
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GATM, IVS3DS, G-T, +1
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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> rs80338738 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338738;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/rs80338738?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=rs80338738" 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=rs80338738" 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=RCV000020462 OR RCV005007885" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020462, RCV005007885" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020462...</a>
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<span class="mim-text-font">
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<p>In a Chinese girl with cerebral creatine deficiency syndrome-3 (CCDS3; <a href="/entry/612718">612718</a>), <a href="#11" class="mim-tip-reference" title="Ndika, J. D. T., Johnston, K., Barkovich, J. A., Wirt, M. D., O'Neill, P., Betsalel, O. T., Jakobs, C., Salomons, G. S. <strong>Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency.</strong> Molec. Genet. Metab. 106: 48-54, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22386973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22386973</a>] [<a href="https://doi.org/10.1016/j.ymgme.2012.01.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22386973">Ndika et al. (2012)</a> identified a homozygous G-to-T transversion in intron 3 of the GATM gene (c.484+1G-T), resulting in a splice site and a truncated protein lacking exon 3 (Ala97ValfsTer11). The mutant transcript was subject to nonsense-mediated mRNA decay. Each unaffected parent was heterozygous for the mutation. GATM activity was not detectable in patient cells. The patient showed significant developmental progress after early and intense treatment with creatine supplementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22386973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</strong>
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<span class="mim-text-font">
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<div style="float: left;">
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GATM, TYR203SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514709 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514709;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=rs397514709" 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=rs397514709" 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=RCV000049334" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049334" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049334</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sisters, born of consanguineous parents, with cerebral creatine deficiency syndrome-3 (CCDS3; <a href="/entry/612718">612718</a>), <a href="#12" class="mim-tip-reference" title="Nouioua, S., Cheillan, D., Zaouidi, S., Salomons, G. S., Amedjout, N., Kessaci, F., Boulahdour, N., Hamadouche, T., Tazir, M. <strong>Creatine deficiency syndrome: a treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency.</strong> Neuromusc. Disord. 23: 670-674, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23770102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23770102</a>] [<a href="https://doi.org/10.1016/j.nmd.2013.04.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23770102">Nouioua et al. (2013)</a> identified a homozygous c.608A-C transversion in exon 4 of the GATM gene, resulting in a tyr203-to-ser (Y203S) substitution at a highly conserved residue. Each unaffected parent was heterozygous for the mutation, which was not found in 210 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23770102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 FANCONI RENOTUBULAR SYNDROME 1</strong>
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</span>
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</h4>
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<div>
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<span class="mim-text-font">
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GATM, PRO320SER
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1889443535 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1889443535;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=rs1889443535" 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=rs1889443535" 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=RCV001174509" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001174509" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001174509</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; <a href="/entry/134600">134600</a>), <a href="#13" class="mim-tip-reference" title="Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others. <strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong> J. Am. Soc. Nephrol. 29: 1849-1858, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>] [<a href="https://doi.org/10.1681/ASN.2017111179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29654216">Reichold et al. (2018)</a> identified a heterozygous c.958C-T transition (c.958C-T, NM_001482.1) in the GATM gene, resulting in a pro320-to-ser (P320S) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 FANCONI RENOTUBULAR SYNDROME 1</strong>
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</h4>
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GATM, THR336ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1889422994 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1889422994;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=rs1889422994" 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=rs1889422994" 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=RCV001174510 OR RCV003159183 OR RCV005012585" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001174510, RCV003159183, RCV005012585" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001174510...</a>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; <a href="/entry/134600">134600</a>), <a href="#13" class="mim-tip-reference" title="Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others. <strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong> J. Am. Soc. Nephrol. 29: 1849-1858, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>] [<a href="https://doi.org/10.1681/ASN.2017111179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29654216">Reichold et al. (2018)</a> identified a heterozygous c.1006A-G transition (c.1006A-G, NM_001482.1) in the GATM gene, resulting in a thr336-to-ala (T336A) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<strong>.0008 FANCONI RENOTUBULAR SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1481334244 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1481334244;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/rs1481334244?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=rs1481334244" 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=rs1481334244" 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=RCV001174511 OR RCV004596413" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001174511, RCV004596413" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001174511...</a>
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<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; <a href="/entry/134600">134600</a>), <a href="#13" class="mim-tip-reference" title="Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others. <strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong> J. Am. Soc. Nephrol. 29: 1849-1858, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>] [<a href="https://doi.org/10.1681/ASN.2017111179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29654216">Reichold et al. (2018)</a> identified a heterozygous c.1007C-T transition (c.1007C-T, NM_001482.1) in the GATM gene, resulting in a thr336-to-ile (T336I) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 FANCONI RENOTUBULAR SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1889422661 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1889422661;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=rs1889422661" 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=rs1889422661" 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=RCV001174512 OR RCV001332014 OR RCV002483940" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001174512, RCV001332014, RCV002483940" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001174512...</a>
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<span class="mim-text-font">
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<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; <a href="/entry/134600">134600</a>), <a href="#13" class="mim-tip-reference" title="Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others. <strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong> J. Am. Soc. Nephrol. 29: 1849-1858, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>] [<a href="https://doi.org/10.1681/ASN.2017111179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29654216">Reichold et al. (2018)</a> identified a heterozygous c.1022C-T transition (c.1022C-T, NM_001482.1) in the GATM gene, resulting in a pro341-to-leu (P341L) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Battini2002" class="mim-anchor"></a>
|
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|
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Battini, R., Leuzzi, V., Carducci, C., Tosetti, M., Bianchi, M. C., Item, C. B., Stockler-Ipsiroglu, S., Cioni, G.
|
|
<strong>Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree.</strong>
|
|
Molec. Genet. Metab. 77: 326-331, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12468279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12468279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12468279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s1096-7192(02)00175-0" target="_blank">Full Text</a>]
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Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R.
|
|
<strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong>
|
|
Ann. Neurol. 47: 511-513, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10762163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10762163</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10762163" 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="Choe2013" class="mim-anchor"></a>
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Choe, C., Nabuurs, C., Stockebrand, M. C., Neu, A., Nunes, P., Morellini, F., Sauter, K., Schillemeit, S., Hermans-Borgmeyer, I., Marescau, B., Heerschap, A., Isbrandt, D.
|
|
<strong>L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.</strong>
|
|
Hum. Molec. Genet. 22: 110-123, 2013. Note: Erratum: Hum. Molec. Genet.: 22: 4030 only, 2013.
|
|
|
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23026748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23026748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23026748" 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/dds407" target="_blank">Full Text</a>]
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<a id="Comeaux2013" class="mim-anchor"></a>
|
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|
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|
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Comeaux, M. S., Wang, J., Wang, G., Kleppe, S., Zhang, V. W., Schmitt, E. S., Craigen, W. J., Renaud, D., Sun, Q., Wong, L.-J.
|
|
<strong>Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.</strong>
|
|
Molec. Genet. Metab. 109: 260-268, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23660394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23660394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23660394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2013.04.006" target="_blank">Full Text</a>]
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<a id="Edvardson2010" class="mim-anchor"></a>
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Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M., Katz-Brull, R.
|
|
<strong>L-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.</strong>
|
|
Molec. Genet. Metab. 101: 228-232, 2010.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20682460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20682460</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20682460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2010.06.021" target="_blank">Full Text</a>]
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<a id="Gross2016" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 4/14/2016.
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<a id="Humm1997" class="mim-anchor"></a>
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Humm, A., Fritsche, E., Mann, K., Gohl, M., Huber, R.
|
|
<strong>Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue.</strong>
|
|
Biochem. J. 322: 771-776, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9148748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9148748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9148748" 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/10.1042/bj3220771" target="_blank">Full Text</a>]
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<a id="Humm1994" class="mim-anchor"></a>
|
|
<div class="">
|
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|
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Humm, A., Huber, R., Mann, K.
|
|
<strong>The amino acid sequences of human and pig L-arginine:glycine amidinotransferase.</strong>
|
|
FEBS Lett. 339: 101-107, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8313955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8313955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8313955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0014-5793(94)80394-3" target="_blank">Full Text</a>]
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<a id="Item2001" class="mim-anchor"></a>
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Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G.
|
|
<strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong>
|
|
Am. J. Hum. Genet. 69: 1127-1133, 2001.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11555793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11555793</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11555793[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=11555793" 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/10.1086/323765" target="_blank">Full Text</a>]
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<a id="Mangravite2013" class="mim-anchor"></a>
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Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., Feng, Q., Rieder, M. J., and 11 others.
|
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<strong>A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.</strong>
|
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Nature 502: 377-380, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23995691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23995691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23995691[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=23995691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature12508" target="_blank">Full Text</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="11" class="mim-anchor"></a>
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<a id="Ndika2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ndika, J. D. T., Johnston, K., Barkovich, J. A., Wirt, M. D., O'Neill, P., Betsalel, O. T., Jakobs, C., Salomons, G. S.
|
|
<strong>Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency.</strong>
|
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Molec. Genet. Metab. 106: 48-54, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22386973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22386973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22386973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2012.01.017" 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="Nouioua2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nouioua, S., Cheillan, D., Zaouidi, S., Salomons, G. S., Amedjout, N., Kessaci, F., Boulahdour, N., Hamadouche, T., Tazir, M.
|
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<strong>Creatine deficiency syndrome: a treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency.</strong>
|
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Neuromusc. Disord. 23: 670-674, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23770102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23770102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23770102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2013.04.011" target="_blank">Full Text</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="Reichold2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others.
|
|
<strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong>
|
|
J. Am. Soc. Nephrol. 29: 1849-1858, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29654216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29654216</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29654216" 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/10.1681/ASN.2017111179" target="_blank">Full Text</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="14" class="mim-anchor"></a>
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<a id="Sandell2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sandell, L. L., Guan, X.-J., Ingram, R., Tilghman, S. M.
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<strong>Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 4622-4627, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12671064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12671064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12671064[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=12671064" 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.0230424100" target="_blank">Full Text</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="15" class="mim-anchor"></a>
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<a id="Verma2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Verma, A.
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<strong>Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy.</strong>
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Neurology 75: 186-188, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20625172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20625172</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20625172" 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/10.1212/WNL.0b013e3181e7cabd" 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="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="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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Cassandra L. Kniffin - updated : 06/07/2020
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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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Matthew B. Gross - updated : 04/14/2016<br>Patricia A. Hartz - updated : 1/31/2014<br>Ada Hamosh - updated : 12/3/2013<br>Cassandra L. Kniffin - updated : 7/16/2013<br>Carol A. Bocchini - updated : 4/14/2009<br>Victor A. McKusick - updated : 6/6/2003<br>Victor A. McKusick - updated : 11/27/2001
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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="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Mark H. Paalman : 2/17/1998
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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="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<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 : 06/11/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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ckniffin : 06/07/2020<br>carol : 08/07/2019<br>carol : 09/22/2016<br>mgross : 04/14/2016<br>mcolton : 8/7/2014<br>mcolton : 4/1/2014<br>mgross : 2/4/2014<br>mcolton : 1/31/2014<br>alopez : 12/3/2013<br>carol : 9/10/2013<br>carol : 7/18/2013<br>ckniffin : 7/16/2013<br>carol : 4/14/2009<br>carol : 4/10/2009<br>alopez : 3/17/2004<br>tkritzer : 6/19/2003<br>tkritzer : 6/13/2003<br>terry : 6/6/2003<br>alopez : 12/5/2001<br>alopez : 11/30/2001<br>terry : 11/27/2001<br>alopez : 2/20/1998<br>alopez : 2/17/1998
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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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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<strong>*</strong> 602360
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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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L-ARGININE:GLYCINE AMIDINOTRANSFERASE; GATM
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<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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AGAT
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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>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GATM</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 702440000;
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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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<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: 15q21.1
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|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : 15:45,361,124-45,402,227 </span>
|
|
</em>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
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|
Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
|
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<tbody>
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|
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<tr>
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<td rowspan="2">
|
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<span class="mim-font">
|
|
15q21.1
|
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</span>
|
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</td>
|
|
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<td>
|
|
<span class="mim-font">
|
|
Cerebral creatine deficiency syndrome 3
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612718
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Fanconi renotubular syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
134600
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Creatine and phosphocreatine play important roles in the energy metabolism of muscle and nerve tissues. The enzyme L-arginine:glycine amidinotransferase (GATM; EC 2.1.4.1) catalyzes the transfer of a guanido group from arginine to glycine, forming guanidinoacetic acid, the immediate precursor of creatine. The major sites of creatine biosynthesis are pancreas, kidney, and liver, where GATM appears to be located in mitochondria of cells (summary by Humm et al., 1994). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
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|
|
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|
<span class="mim-text-font">
|
|
<p>Humm et al. (1994) isolated and sequenced Gatm, which they called Agat, from pig kidney mitochondria. Sequence data from the pig Agat polypeptide allowed them to isolate cDNA clones encoding the human enzyme from a kidney carcinoma cDNA library. The largest human cDNA sequence encodes a 423-amino acid polypeptide including a 37-amino acid signal sequence. The mature porcine and human proteins are 94% identical to each other and 36% identical to bacterial L-arginine:inosamine phosphate amidinotransferase. Humm et al. (1997) noted that mitochondrial and cytosolic forms of AGAT are believed to derive from the same gene by alternative splicing. They expressed human AGAT in E. coli and identified its active-site cysteine residue (cys407). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Item et al. (2001) stated that the GATM genomic DNA is 16,858 bp long and contains 9 exons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Item et al. (2001) stated that the human GATM gene is located on chromosome 15q15.3. </p><p>Gross (2016) mapped the GATM gene to chromosome 15q21.1 based on an alignment of the GATM sequence (GenBank BC004141) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p><strong><em>Cerebral Creatine Deficiency Syndrome 3</em></strong></p><p>
|
|
In 2 sisters with cerebral creatine deficiency syndrome-3 (CCDS3; 612718) reported by Bianchi et al. (2000), Item et al. (2001) identified a homozygous trp149-to-ter mutation in the GATM gene (W149X; 602360.0001), resulting in undetectable cDNA, as investigated by RT-PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. In an affected male cousin of the sibs reported by Bianchi et al. (2000), Battini et al. (2002) identified homozygosity for the same W149X mutation. </p><p>In 2 sibs, born of unrelated Yemenite Jewish parents, with cerebral creatine deficiency syndrome-3, Edvardson et al. (2010) identified a homozygous truncating mutation in the GATM gene (602360.0002). </p><p><strong><em>Fanconi Renotubular Syndrome 1</em></strong></p><p>
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|
In 28 affected members from 5 unrelated families with Fanconi renotubular syndrome-1 (FRTS1; 134600), Reichold et al. (2018) identified 4 different heterozygous missense mutations in the GATM gene (P320S, 602360.0006; T336A, 602360.0007; T336I, 602360.0008; and P34L, 602360.0009). The mutations, which were found by a combination of linkage analysis and candidate gene sequencing, next-generation gene sequencing, and exome sequencing, were confirmed by Sanger sequencing; the variants segregated with the disorder in all families. In silico modeling suggested that the mutations may adversely affect protein folding and possibly predispose the mutant protein to aggregation. Overexpression of the mutations in renal proximal tubule cells resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. Cells transfected with the T336A mutation showed decreased mitochondrial turnover rate, increased reactive oxygen species (ROS), activation of the inflammasome, including elevated IL18 (600953), increased levels of fibronectin and actin mRNA, and increased cell death compared to controls. These findings provided a mechanistic link between kidney fibrosis and progressive renal failure observed in the patients. Examination of Gatm-null mice showed no evidence of aminoaciduria or glycosuria, consistent with no effect on renal proximal tubular function. However, treatment of rats with oral creatine reduced renal Gatm expression and protein levels, suggesting that it could be a possible intervention to suppress the endogenous production of mutant GATM and dampen the formation of deleterious mitochondrial deposits. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
Mangravite et al. (2013) identified a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment. This analysis identified 6 expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the GATM gene, which encodes the rate-limiting enzyme in creatine synthesis. Mangravite et al. (2013) found this locus to be associated with incidence of statin-induced myotoxicity in 2 separate populations (metaanalysis odds ratio = 0.60). Furthermore, Mangravite et al. (2013) found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sandell et al. (2003) demonstrated in the mouse that Gatm, which is expressed during development, is imprinted in the placenta and yolk sac, but not in embryonic tissues. The Gatm gene maps to mouse chromosome 2 in a region that had not previously been shown to contain imprinted genes. To determine whether Gatm is located in a cluster of imprinted genes, Sandell et al. (2003) investigated the expression pattern of genes located near Gatm: Duox1 (606758), Duox2 (606759), Slc28a2 (606208), Slc30a4 (602095), and a transcript corresponding to LOC214616 and found no evidence that any is imprinted in placenta. These data were the first to link creatine metabolism with imprinting and the parental 'tug-of-war' for energy resources during development. Although many imprinted genes are associated with differentially methylated CpG islands, the Gatm gene resides in apparent isolation from other imprinted genes and is associated with an unmethylated CpG island. </p><p>Choe et al. (2013) found that Gatm -/- mice were born at the expected mendelian ratio. Gatm -/- mice did not require special treatment for survival, but they showed multiple abnormalities, and both sexes were infertile. Gatm -/- mice were lean and short with markedly reduced body mass index, accompanied by low serum leptin (LEP; 164160) levels and the expected creatine deficiency. Gatm -/- mice showed increased food intake compared with controls. They also showed reduced locomotor activity, reduced body tension, and severe scoliosis, indicating chronic muscular hypotonia. Creatine deficiency in Gatm -/- mice resulted in chronic Ampk (see 602739) activation in skeletal muscle, white adipose tissue, liver, and hypothalamus, concomitant with reduced muscular nucleoside triphosphate content and inhibition of acetyl-CoA carboxylase (see 200350) in muscle, adipose, and liver. Conversely, creatine deficiency improved glucose tolerance in Gatm -/- mice and protected them from metabolic syndrome induced by a high-fat diet. Oral creatine administration largely reversed the phenotype of Gatm -/- mice. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</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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GATM, TRP149TER
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<br />
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SNP: rs80338737,
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gnomAD: rs80338737,
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ClinVar: RCV000007725
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sisters with cerebral creatine deficiency syndrome-3 (CCDS3; 612718) reported by Bianchi et al. (2000), Item et al. (2001) identified a homozygous 9297G-A transition, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (W149X) of the GATM gene. </p><p>In an affected cousin of the sibs reported by Bianchi et al. (2000), Battini et al. (2002) identified homozygosity for the same W149X mutation; his parents and 10 additional subjects in the pedigree were heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</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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GATM, 1-BP INS, 1111A
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<br />
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SNP: rs397515542,
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gnomAD: rs397515542,
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ClinVar: RCV000049331
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs, born of unrelated Yemenite Jewish parents, with cerebral creatine deficiency syndrome-3 (CCDS3; 612718), Edvardson et al. (2010) identified a homozygous 1-bp insertion (1111insA) in the GATM gene, resulting in a frameshift and premature termination at codon 376. Each unaffected parent was heterozygous for the mutation, which was not found in 57 ethnic controls. Both patients showed delayed psychomotor development in infancy with poor speech acquisition. Each also had symptoms of a myopathy, with easy fatigability and predominantly proximal muscle weakness and atrophy. Brain MRS showed decreased creatine, and urine guanidinoacetate levels were low. Treatment with oral creatine resulted in clinical improvement and increased cerebral creatine levels. </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>.0003 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</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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GATM, ARG169TER
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<br />
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SNP: rs397514708,
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gnomAD: rs397514708,
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ClinVar: RCV000049332, RCV002490622
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 Jordanian sibs, born of consanguineous parents, with cerebral creatine deficiency syndrome 3 (CCDS3; 612718), Verma (2010) identified a homozygous arg169-to-ter (R169X) substitution in the GATM gene. Both patients showed delayed development in early childhood and began to show progressive proximal muscle weakness with features of a myopathy in their late teens. Laboratory studies showed undetectable GAA levels. Treatment with oral creatine supplementation resulted in dramatic improvement of muscle strength, but speech and cognitive impairment were unchanged. </p><p>Comeaux et al. (2013) reported 2 sibs with CCDSD3 who were homozygous for a c.505C-T transition in exon 4 of the GATM gene, resulting in an R169X substitution. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
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</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, IVS3DS, G-T, +1
|
|
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|
|
|
<br />
|
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|
|
SNP: rs80338738,
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|
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|
|
gnomAD: rs80338738,
|
|
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|
|
ClinVar: RCV000020462, RCV005007885
|
|
|
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|
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</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Chinese girl with cerebral creatine deficiency syndrome-3 (CCDS3; 612718), Ndika et al. (2012) identified a homozygous G-to-T transversion in intron 3 of the GATM gene (c.484+1G-T), resulting in a splice site and a truncated protein lacking exon 3 (Ala97ValfsTer11). The mutant transcript was subject to nonsense-mediated mRNA decay. Each unaffected parent was heterozygous for the mutation. GATM activity was not detectable in patient cells. The patient showed significant developmental progress after early and intense treatment with creatine supplementation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CEREBRAL CREATINE DEFICIENCY SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, TYR203SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514709,
|
|
|
|
|
|
|
|
ClinVar: RCV000049334
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sisters, born of consanguineous parents, with cerebral creatine deficiency syndrome-3 (CCDS3; 612718), Nouioua et al. (2013) identified a homozygous c.608A-C transversion in exon 4 of the GATM gene, resulting in a tyr203-to-ser (Y203S) substitution at a highly conserved residue. Each unaffected parent was heterozygous for the mutation, which was not found in 210 control alleles. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 FANCONI RENOTUBULAR SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, PRO320SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1889443535,
|
|
|
|
|
|
|
|
ClinVar: RCV001174509
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; 134600), Reichold et al. (2018) identified a heterozygous c.958C-T transition (c.958C-T, NM_001482.1) in the GATM gene, resulting in a pro320-to-ser (P320S) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 FANCONI RENOTUBULAR SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, THR336ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1889422994,
|
|
|
|
|
|
|
|
ClinVar: RCV001174510, RCV003159183, RCV005012585
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; 134600), Reichold et al. (2018) identified a heterozygous c.1006A-G transition (c.1006A-G, NM_001482.1) in the GATM gene, resulting in a thr336-to-ala (T336A) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 FANCONI RENOTUBULAR SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, THR336ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1481334244,
|
|
|
|
|
|
gnomAD: rs1481334244,
|
|
|
|
|
|
ClinVar: RCV001174511, RCV004596413
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; 134600), Reichold et al. (2018) identified a heterozygous c.1007C-T transition (c.1007C-T, NM_001482.1) in the GATM gene, resulting in a thr336-to-ile (T336I) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 FANCONI RENOTUBULAR SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GATM, PRO341LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1889422661,
|
|
|
|
|
|
|
|
ClinVar: RCV001174512, RCV001332014, RCV002483940
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Fanconi renotubular syndrome-1 (FRTS1; 134600), Reichold et al. (2018) identified a heterozygous c.1022C-T transition (c.1022C-T, NM_001482.1) in the GATM gene, resulting in a pro341-to-leu (P341L) substitution at a highly conserved residue. Overexpression of the mutation in a renal proximal tubule cell resulted in abnormal and elongated mitochondria containing GATM-positive fibrillary aggregates, similar to the deposits observed in the proximal tubules of patient renal biopsies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
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<br />
|
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Battini, R., Leuzzi, V., Carducci, C., Tosetti, M., Bianchi, M. C., Item, C. B., Stockler-Ipsiroglu, S., Cioni, G.
|
|
<strong>Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree.</strong>
|
|
Molec. Genet. Metab. 77: 326-331, 2002.
|
|
|
|
|
|
[PubMed: 12468279]
|
|
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|
|
[Full Text: https://doi.org/10.1016/s1096-7192(02)00175-0]
|
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|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., Canapicchi, R.
|
|
<strong>Reversible brain creatine deficiency in two sisters with normal blood creatine level.</strong>
|
|
Ann. Neurol. 47: 511-513, 2000.
|
|
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|
|
[PubMed: 10762163]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
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Choe, C., Nabuurs, C., Stockebrand, M. C., Neu, A., Nunes, P., Morellini, F., Sauter, K., Schillemeit, S., Hermans-Borgmeyer, I., Marescau, B., Heerschap, A., Isbrandt, D.
|
|
<strong>L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.</strong>
|
|
Hum. Molec. Genet. 22: 110-123, 2013. Note: Erratum: Hum. Molec. Genet.: 22: 4030 only, 2013.
|
|
|
|
|
|
[PubMed: 23026748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/dds407]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Comeaux, M. S., Wang, J., Wang, G., Kleppe, S., Zhang, V. W., Schmitt, E. S., Craigen, W. J., Renaud, D., Sun, Q., Wong, L.-J.
|
|
<strong>Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.</strong>
|
|
Molec. Genet. Metab. 109: 260-268, 2013.
|
|
|
|
|
|
[PubMed: 23660394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2013.04.006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M., Katz-Brull, R.
|
|
<strong>L-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.</strong>
|
|
Molec. Genet. Metab. 101: 228-232, 2010.
|
|
|
|
|
|
[PubMed: 20682460]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2010.06.021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 4/14/2016.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Humm, A., Fritsche, E., Mann, K., Gohl, M., Huber, R.
|
|
<strong>Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue.</strong>
|
|
Biochem. J. 322: 771-776, 1997.
|
|
|
|
|
|
[PubMed: 9148748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bj3220771]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Humm, A., Huber, R., Mann, K.
|
|
<strong>The amino acid sequences of human and pig L-arginine:glycine amidinotransferase.</strong>
|
|
FEBS Lett. 339: 101-107, 1994.
|
|
|
|
|
|
[PubMed: 8313955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(94)80394-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Item, C. B., Stockler-Ipsiroglu, S., Stromberger, C., Muhl, A., Alessandri, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., Cioni, G.
|
|
<strong>Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.</strong>
|
|
Am. J. Hum. Genet. 69: 1127-1133, 2001.
|
|
|
|
|
|
[PubMed: 11555793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/323765]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., Feng, Q., Rieder, M. J., and 11 others.
|
|
<strong>A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.</strong>
|
|
Nature 502: 377-380, 2013.
|
|
|
|
|
|
[PubMed: 23995691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12508]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ndika, J. D. T., Johnston, K., Barkovich, J. A., Wirt, M. D., O'Neill, P., Betsalel, O. T., Jakobs, C., Salomons, G. S.
|
|
<strong>Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency.</strong>
|
|
Molec. Genet. Metab. 106: 48-54, 2012.
|
|
|
|
|
|
[PubMed: 22386973]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2012.01.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nouioua, S., Cheillan, D., Zaouidi, S., Salomons, G. S., Amedjout, N., Kessaci, F., Boulahdour, N., Hamadouche, T., Tazir, M.
|
|
<strong>Creatine deficiency syndrome: a treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency.</strong>
|
|
Neuromusc. Disord. 23: 670-674, 2013.
|
|
|
|
|
|
[PubMed: 23770102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2013.04.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., and 42 others.
|
|
<strong>Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure.</strong>
|
|
J. Am. Soc. Nephrol. 29: 1849-1858, 2018.
|
|
|
|
|
|
[PubMed: 29654216]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1681/ASN.2017111179]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sandell, L. L., Guan, X.-J., Ingram, R., Tilghman, S. M.
|
|
<strong>Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 4622-4627, 2003.
|
|
|
|
|
|
[PubMed: 12671064]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0230424100]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verma, A.
|
|
<strong>Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy.</strong>
|
|
Neurology 75: 186-188, 2010.
|
|
|
|
|
|
[PubMed: 20625172]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e3181e7cabd]
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