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<title>
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Entry
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- *615320 - GDP-MANNOSE PYROPHOSPHORYLASE B; GMPPB
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- OMIM
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*615320</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/615320">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
|
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
|
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000173540;t=ENST00000308388" 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=29925" 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=615320" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000173540;t=ENST00000308388" 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_013334,NM_021971" 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_021971" 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=615320" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
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</div>
|
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</div>
|
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</div>
|
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
|
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</span>
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</div>
|
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.proteinatlas.org/search/GMPPB" 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/5052351,10436672,12654611,14125010,119585416,119585417,119585418,119585419,158256832,160013885,259439484,259472469,300544869,300634383,1677530614,1890258878" 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/Q9Y5P6" 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=29925" 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=ENSG00000173540;t=ENST00000308388" 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=GMPPB" 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=GMPPB" 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+29925" 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/GMPPB" 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:29925" 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/29925" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr3&hgg_gene=ENST00000308388.7&hgg_start=49719916&hgg_end=49723951&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:22932" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615320[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=615320[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/GMPPB/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/ENSG00000173540" 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=GMPPB" 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=GMPPB" 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=GMPPB" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GMPPB&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/PA134875590" 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:22932" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0037279.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2660880" 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/GMPPB#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:2660880" 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/29925/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=29925" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00016583;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040801-234" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<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:29925" 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=GMPPB&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> 732930007<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>
|
|
615320
|
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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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GDP-MANNOSE PYROPHOSPHORYLASE B; GMPPB
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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">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
GDP-MANNOSE PYROPHOSPHORYLASE, BETA SUBUNIT<br />
|
|
GMPP-BETA
|
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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>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GMPPB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GMPPB</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/3/319?start=-3&limit=10&highlight=319">3p21.31</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:49719916-49723951&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">3:49,719,916-49,723,951</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>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<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">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615350,615351,615352" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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</th>
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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<a href="/geneMap/3/319?start=-3&limit=10&highlight=319">
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3p21.31
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<span class="mim-font">
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14
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<span class="mim-font">
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<a href="/entry/615350"> 615350 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14
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<span class="mim-font">
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<a href="/entry/615351"> 615351 </a>
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</td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615352"> 615352 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/615320" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/615320" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>The GMPPB gene encodes the beta subunit of an essential enzyme, GDP-mannose pyrophosphorylase (<a href="https://enzyme.expasy.org/EC/2.7.7.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.7.13</a>), that catalyzes the conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose, a major mannosyl donor for mannose-containing polymers (<a href="#7" class="mim-tip-reference" title="Ning, B., Elbein, A. D. <strong>Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase: evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.</strong> Europ. J. Biochem. 267: 6866-6874, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11082198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11082198</a>] [<a href="https://doi.org/10.1046/j.1432-1033.2000.01781.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11082198">Ning and Elbein, 2000</a>). GDP-mannose is required in 4 glycosylation pathways, including O-mannosylation of membrane and secretory glycoproteins, such as alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) (summary by <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11082198+23768512" 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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<br />
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<div>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<p>By searching databases for sequences similar to porcine Gmpp-beta, <a href="#7" class="mim-tip-reference" title="Ning, B., Elbein, A. D. <strong>Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase: evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.</strong> Europ. J. Biochem. 267: 6866-6874, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11082198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11082198</a>] [<a href="https://doi.org/10.1046/j.1432-1033.2000.01781.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11082198">Ning and Elbein (2000)</a> identified human GMPPB, as well as GMPPB orthologs in several lower species, including nematode, yeast, and plants. The 360-amino acid human protein shares 96% identity with porcine Gmpp-beta. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11082198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The GMPPB protein contains 2 main functional domains: a nucleotidyl transferase domain and a bacterial transferase hexapeptide domain. <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> determined that the GMPPB gene is transcribed as 2 isoforms in human tissues. The longer isoform (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=NM_021971.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">NM_021971.1</a>) was strongly expressed in all fetal and adult tissues tested, including brain and skeletal muscle, whereas the shorter isoform (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=NM_013334.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">NM_013334.2</a>) was weakly expressed in the tissues tested. There appeared to be no developmental difference in the expression of the 2 isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, <a href="#6" class="mim-tip-reference" title="Nagase, T., Nakayama, M., Nakajima, D., Kikuno, R., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 8: 85-95, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11347906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11347906</a>] [<a href="https://doi.org/10.1093/dnares/8.2.85" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11347906">Nagase et al. (2001)</a> obtained a clone, which they designated KIAA1851, containing 2 coding regions separated by 2.4 kb. They identified the upstream coding region as that of GMPPB and suggested that KIAA1851 may represent a read-through transcript of the GMPPB gene. <a href="#4" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. 3/12/2014."None>Hartz (2014)</a> determined that the KIAA1851 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB058754" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB058754</a>) includes the sequence of AMIGO3 (<a href="/entry/615691">615691</a>) (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AY237003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AY237003</a>) in addition to that of GMPPB. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11347906" 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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<br />
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Gene Structure</strong>
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<p>The coding DNA sequence of one isoform of the GMPPB gene (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=NM_021971.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">NM_021971.1</a>) contains 10 exons, whereas that of another isoform (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=NM_013334.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">NM_013334.2</a>) contains 8 exons (<a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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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<br />
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<div>
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<strong>Mapping</strong>
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<p><a href="#3" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. 7/19/2013."None>Hartz (2013)</a> mapped the GMPPB gene to chromosome 3p21.31 based on an alignment of the GMPPB sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB058754" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB058754</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#7" class="mim-tip-reference" title="Ning, B., Elbein, A. D. <strong>Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase: evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.</strong> Europ. J. Biochem. 267: 6866-6874, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11082198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11082198</a>] [<a href="https://doi.org/10.1046/j.1432-1033.2000.01781.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11082198">Ning and Elbein (2000)</a> found that recombinant porcine Gmpp-beta catalyzed bidirectional conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose. Compared with purified pig liver Gmpp, which was a dimer of alpha and beta subunits, recombinant Gmpp-beta showed much lower activity as a GDP-glucose pyrophosphorylase (<a href="https://enzyme.expasy.org/EC/2.7.7.34" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.7.34</a>). Divalent cations, particularly Mn(2+), enhanced the Gmpp-beta reaction, whereas Mg(2+) was the preferred cofactor for the endogenous dimeric enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11082198" 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>By exome sequencing combined with Sanger sequencing of 8 unrelated patients with various forms of congenital muscular dystrophy, <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> identified 8 different mutations in the GMPPB gene (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=NM_02197.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">NM_02197.1</a>) (<a href="#0001">615320.0001</a>-<a href="#0008">615320.0008</a>). All mutations occurred in homozygous or compound heterozygous state and segregated with the disorder in the families in whom parental DNA was available. All affected individuals had at least 1 mutation affecting the highly conserved nucleotidyl transferase domain. The phenotype was highly variable. The most severely affected patient had muscle weakness at birth with severely delayed psychomotor development, retinal dysfunction, and pontocerebellar hypoplasia, reminiscent of muscle-eye-brain disease and consistent with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; <a href="/entry/615350">615350</a>). Four patients presented with a slightly milder phenotype with onset of muscle weakness in the first months of life with milder intellectual disability with or without cerebellar hypoplasia, consistent with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual disability type B14 (MDDGB14; <a href="/entry/615351">615351</a>). The least severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>), also known as LGMDR19 and LGMD2T, was present in 3 unrelated patients, 1 of whom had onset at age 4 and normal intellectual function. Variable features seen in some patients included microcephaly, seizures, cataracts, and cardiac dysfunction. All patients had dystrophic features on muscle biopsy, and immunohistochemical and flow cytometric analysis of patient cells showed reduced glycosylation of alpha-dystroglycan. Overexpression of wildtype GMPPB in fibroblasts from an affected individual partially restored glycosylation of DAG1. Whereas wildtype GMPPB localized to the cytoplasm, 5 of the identified missense mutations caused formation of aggregates in the cytoplasm or near membrane protrusions. Knockdown of the GMPPB ortholog in zebrafish caused structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of DAG1. None of the patients had evidence of abnormal serum transferrin glycoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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 7 patients from 5 unrelated families with MDDGC14 with features of congenital myasthenic syndrome, <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a> identified homozygous or compound heterozygous mutations in the GMPPB gene (see, e.g., <a href="#0007">615320.0007</a>; <a href="#0009">615320.0009</a>-<a href="#0011">615320.0011</a>). The mutations in the first patient were found by whole-exome sequencing; mutations in subsequent patients were found by screening of the GMPPB gene in a cohort of patients diagnosed with congenital myasthenic syndrome. The patients with GMPPB mutations showed decrement of compound muscle action potentials on repetitive nerve stimulation as well as myopathic findings on muscle biopsy and increased serum creating kinase. The findings indicated that GMPPB mutations can lead to a wide spectrum of clinical features including defects in neuromuscular transmission. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26133662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> found that zebrafish gmppb is expressed throughout development. Morpholino knockdown of gmppb in zebrafish resulted in smaller embryos with multiple anomalies, including bent tails, hypopigmentation, microphthalmia, hydrocephalus, and reduced motility. Muscle fibers in mutant zebrafish were sparse and disorganized, and the myosepta were damaged or incompletely developed. There was also evidence of sarcolemmal damage. Immunostaining showed defective glycosylation of DAG1 associated with abnormal structure of the basement membrane. These findings were reminiscent of the muscular dystrophy phenotype found in humans with GMPPB mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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>.0001 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 14</strong>
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<p>In a patient (P1) with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; <a href="/entry/615350">615350</a>), <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> identified compound heterozygous mutations in the GMPPB gene: a c.1000G-A transition resulting in an asp334-to-asn (D334N) substitution at a highly conserved residue at the C terminus, and a c.220C-T transition resulting in an arg74-to-ter (R74X; <a href="#0002">615320.0002</a>) substitution. The mutations were identified by exome sequencing and confirmed by Sanger sequencing. Each unaffected parent was heterozygous for 1 of the mutations. Transfection of the D334N mutation into myoblasts caused the protein to form cytoplasmic aggregates. The R74X mutation, which occurs in the nucleotidyl transferase domain, is predicted to cause a severely truncated protein and nonsense-mediated mRNA. The patient had severely delayed psychomotor development, sensorineural hearing loss, retinal dysfunction, and pontine and cerebellar hypoplasia on brain MRI. Studies of the patient's skeletal muscle and fibroblasts showed decreased glycosylation of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>), which was partially restored by transfection of wildtype GMPPB. An unrelated patient (P2) with a somewhat less severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) with mental retardation, was found to be compound heterozygous for D334N and a c.64C-T transition resulting in a pro22-to-ser (P22S; <a href="#0003">615320.0003</a>) substitution at a highly conserved residue in the nucleotidyl transferase domain. Transfection of the P22S mutation into myoblasts caused the protein to aggregate near membrane protrusions into the cytoplasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>For discussion of the arg74-to-ter (R74X) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; <a href="/entry/615350">615350</a>) by <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a>, see <a href="#0001">615320.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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">rs397509424 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397509424;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=rs397509424" 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=rs397509424" 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=RCV000054435" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054435" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054435</a>
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<p>For discussion of the pro22-to-ser (P22S) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) by <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a>, see <a href="#0001">615320.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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>.0004 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</strong>
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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14, INCLUDED
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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> rs397509425 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397509425;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/rs397509425?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=rs397509425" 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=rs397509425" 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=RCV000054436 OR RCV000054437 OR RCV000200261 OR RCV000503216 OR RCV000623944 OR RCV001781385" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054436, RCV000054437, RCV000200261, RCV000503216, RCV000623944, RCV001781385" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054436...</a>
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<p>In 2 unrelated Mexican patients (P3 and P4) with congenital muscular dystrophy-dystroglycanopathy with mental retardation type B14 (MDDGB14; <a href="/entry/615351">615351</a>), <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> identified a homozygous c.553C-T transition in the GMPPB gene, resulting in an arg185-to-cys (R185C) substitution at a highly conserved residue in the nucleotidyl transferase domain. The mutations were found in 1 of the patients by exome sequencing and confirmed in both patients by Sanger sequencing. The unaffected mother of 1 of the patients was heterozygous for the mutation. Exome sequencing of an Egyptian patient (P8) with a somewhat less severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) with mental retardation and cardiorespiratory dysfunction, also yielded a homozygous R185C mutation. The unaffected parents of this patient were heterozygous for the mutation. Transfection of the R185C mutation into myoblasts caused the protein to remain evenly distributed in the cytoplasm and had no discernible changes compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</strong>
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GMPPB, PRO32LEU
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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> rs397509426 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397509426;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/rs397509426?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=rs397509426" 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=rs397509426" 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=RCV000054438 OR RCV000209926 OR RCV000493576 OR RCV000684892" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054438, RCV000209926, RCV000493576, RCV000684892" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054438...</a>
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<p>In 2 unrelated Italian girls (P5 and P6) with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development type B14 (MDDGB14; <a href="/entry/615351">615351</a>), previously reported by <a href="#5" class="mim-tip-reference" title="Messina, S., Tortorella, G., Concolino, D., Spano, M., D'Amico, A., Bruno, C., Santorelli, F. M., Mercuri, E., Bertini, E. <strong>Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy.</strong> Neurology 73: 1599-1601, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19901254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19901254</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181c0d47a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19901254">Messina et al. (2009)</a>, <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> identified compound heterozygosity for 2 mutations in the GMPPB gene: a c.95C-T transition resulting in a pro32-to-leu (P32L) substitution at a highly conserved residue in the nucleotidyl transferase domain, and a c.860G-A transition resulting in an arg287-to-gln (R287Q; <a href="#0006">615320.0006</a>) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. P32L had not been reported, and R287Q is rare and has a minor allele frequency of less than or equal to 0.001 in database controls. Transfection of both mutations into myoblasts caused the protein to form aggregates within the cytoplasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19901254+23768512" 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>.0006 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</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> rs202160208 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202160208;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/rs202160208?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=rs202160208" 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=rs202160208" 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=RCV000054439 OR RCV000209893 OR RCV000520160 OR RCV000553832 OR RCV001266808 OR RCV001542745 OR RCV001814035 OR RCV003407434" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054439, RCV000209893, RCV000520160, RCV000553832, RCV001266808, RCV001542745, RCV001814035, RCV003407434" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054439...</a>
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<p>For discussion of the arg287-to-gln (R287Q) mutation in the GMPPB gene that was found in compound heterozygous state in 2 patients with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development type B14 (MDDGB14; <a href="/entry/615351">615351</a>) by <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a>, see <a href="#0005">615320.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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>.0007 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</strong>
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GMPPB, ASP27HIS
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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> rs142336618 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs142336618;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/rs142336618?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=rs142336618" 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=rs142336618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 6-year-old English boy (P7) with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) without mental retardation, <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a> identified compound heterozygous mutations in the GMPPB gene: a c.79G-C transversion, resulting in an asp27-to-his (D27H) substitution at a highly conserved residue in the nucleotidyl transferase domain, and a c.988G-A transition, resulting in a val330-to-ile (V330I; <a href="#0008">615320.0008</a>) substitution at a highly conserved residue in the C terminus. Each unaffected parent was heterozygous for 1 of the mutations. Both variants are rare, with minor allele frequencies of less than or equal to 0.001 in database controls. Transfection of the D27H mutation into myoblasts caused the protein to remain evenly distributed in the cytoplasm and had no discernible changes compared to wildtype, whereas transfection of V330I caused the protein to form aggregates within the cytoplasm. The patient had a mild form of the disorder, presenting only with exercise intolerance at age 4 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For discussion of the D27H mutation (c.79G-C, NM_021971) in the GMPPB gene that was found in compound heterozygous state in patients with MDDGC14 with features of congenital myasthenic syndrome by <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a>, see <a href="#0009">615320.0009</a> and <a href="#0010">615320.0010</a>. <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a> found the D27H mutation at a low frequency (0.077%) in the Exome Variant Server database. D27H mutant protein expression was decreased compared to wildtype in transfected HEK293 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26133662" 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>NM_021971</p>
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<strong>.0008 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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> rs199922550 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199922550;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/rs199922550?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=rs199922550" 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=rs199922550" 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=RCV000054441 OR RCV000440664 OR RCV000501778 OR RCV000623470 OR RCV000651278 OR RCV001330455" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054441, RCV000440664, RCV000501778, RCV000623470, RCV000651278, RCV001330455" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054441...</a>
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<p>For discussion of the val330-to-ile (V330I) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) without mental retardation by <a href="#2" class="mim-tip-reference" title="Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others. <strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 93: 29-41, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23768512">Carss et al. (2013)</a>, see <a href="#0007">615320.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768512" 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 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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> rs142908436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs142908436;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/rs142908436?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=rs142908436" 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=rs142908436" 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=RCV000211126 OR RCV000609930 OR RCV000698947 OR RCV001508147" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000211126, RCV000609930, RCV000698947, RCV001508147" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000211126...</a>
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<p>In a 48-year-old woman with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) with features of congenital myasthenic syndrome, <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a> identified compound heterozygous mutations in the GMPPB gene: a c.859C-T transition (c.859C-T, NM_021971), resulting in an arg287-to-trp (R287W) substitution, and D27H (<a href="#0007">615320.0007</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Both mutations were found at low frequencies in the Exome Variant Server database (0.077% for D27H and 0.008% for R287W). In transfected HEK293 cells, R287W protein expression was undetectable, whereas D27H expression was decreased compared to wildtype. In a transfected mouse muscle cell line, R287W mutant protein expression was drastically reduced, and the protein that was expressed displayed a punctate pattern of localization, suggesting abnormal protein aggregation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26133662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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> rs875989850 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs875989850;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/rs875989850?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=rs875989850" 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=rs875989850" 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=RCV000211128 OR RCV000430158 OR RCV002515608" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000211128, RCV000430158, RCV002515608" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000211128...</a>
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<p>In a 28-year-old woman with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) with features of congenital myasthenic syndrome, <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a> identified compound heterozygous mutations in the GMPPB gene: a c.760G-A transition (c.760G-A, NM_021971), resulting in a val254-to-met (V254M) substitution at a conserved residue and D27H (<a href="#0007">615320.0007</a>). The mutations segregated with the disorder in the family. In transfected HEK293 cells, V254M protein expression was undetectable, whereas D27H expression was decreased compared to wildtype. In a transfected mouse muscle cell line, V254M mutant protein expression was drastically reduced, and the protein that was expressed displayed a punctate pattern of localization, suggesting abnormal protein aggregation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26133662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</strong>
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<div style="float: left;">
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GMPPB, PRO103LEU
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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> rs875989851 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs875989851;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/rs875989851?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=rs875989851" 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=rs875989851" 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=RCV000211125 OR RCV001814120" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000211125, RCV001814120" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000211125...</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 3 adult sibs, born of consanguineous Iranian parents, with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; <a href="/entry/615352">615352</a>) with features of a congenital myasthenic syndrome, <a href="#1" class="mim-tip-reference" title="Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others. <strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong> Brain 138: 2493-2504, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awv185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26133662">Belaya et al. (2015)</a> identified a homozygous c.308C-T transition (c.308C-T, NM_021971) in the GMPPB gene, resulting in a pro103-to-leu (P103L) substitution at a conserved residue in the nucleotidyl transferase domain. The mutation segregated with the disorder in the family. In transfected HEK293 cells, P103L protein expression was slightly decreased compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26133662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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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="references"class="mim-anchor"></a>
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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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</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 id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<ol>
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<li>
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<a id="1" class="mim-anchor"></a>
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<a id="Belaya2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others.
|
|
<strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong>
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|
Brain 138: 2493-2504, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26133662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26133662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26133662[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=26133662" 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/brain/awv185" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Carss2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others.
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<strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong>
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Am. J. Hum. Genet. 93: 29-41, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768512</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23768512[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=23768512" 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.ajhg.2013.05.009" 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="3" class="mim-anchor"></a>
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<a id="Hartz2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 7/19/2013.
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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="4" class="mim-anchor"></a>
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<a id="Hartz2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 3/12/2014.
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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="5" class="mim-anchor"></a>
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<a id="Messina2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Messina, S., Tortorella, G., Concolino, D., Spano, M., D'Amico, A., Bruno, C., Santorelli, F. M., Mercuri, E., Bertini, E.
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|
<strong>Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy.</strong>
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|
Neurology 73: 1599-1601, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19901254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19901254</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19901254" 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.0b013e3181c0d47a" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Nagase2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nagase, T., Nakayama, M., Nakajima, D., Kikuno, R., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 8: 85-95, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11347906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11347906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11347906" 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/dnares/8.2.85" target="_blank">Full Text</a>]
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Ning2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ning, B., Elbein, A. D.
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<strong>Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase: evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.</strong>
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Europ. J. Biochem. 267: 6866-6874, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11082198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11082198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11082198" 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/10.1046/j.1432-1033.2000.01781.x" target="_blank">Full Text</a>]
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</p>
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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 : 5/11/2016
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 3/12/2014<br>Cassandra L. Kniffin - updated : 7/31/2013
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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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Patricia A. Hartz : 7/19/2013
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</span>
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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 class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/19/2020
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/25/2018<br>alopez : 05/13/2016<br>ckniffin : 5/11/2016<br>alopez : 7/22/2015<br>mcolton : 7/21/2015<br>carol : 10/20/2014<br>mcolton : 10/15/2014<br>carol : 10/3/2014<br>mgross : 3/12/2014<br>mcolton : 3/12/2014<br>carol : 10/7/2013<br>carol : 8/8/2013<br>carol : 8/6/2013<br>carol : 8/6/2013<br>ckniffin : 7/31/2013<br>mgross : 7/19/2013
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</span>
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</div>
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 615320
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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GDP-MANNOSE PYROPHOSPHORYLASE B; GMPPB
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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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<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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GDP-MANNOSE PYROPHOSPHORYLASE, BETA SUBUNIT<br />
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GMPP-BETA
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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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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GMPPB</em></strong>
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</span>
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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> 732930007;
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</span>
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</p>
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<div>
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<br />
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 3p21.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:49,719,916-49,723,951 </span>
|
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
|
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Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
3p21.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615350
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615351
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615352
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The GMPPB gene encodes the beta subunit of an essential enzyme, GDP-mannose pyrophosphorylase (EC 2.7.7.13), that catalyzes the conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose, a major mannosyl donor for mannose-containing polymers (Ning and Elbein, 2000). GDP-mannose is required in 4 glycosylation pathways, including O-mannosylation of membrane and secretory glycoproteins, such as alpha-dystroglycan (DAG1; 128239) (summary by Carss et al., 2013). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By searching databases for sequences similar to porcine Gmpp-beta, Ning and Elbein (2000) identified human GMPPB, as well as GMPPB orthologs in several lower species, including nematode, yeast, and plants. The 360-amino acid human protein shares 96% identity with porcine Gmpp-beta. </p><p>The GMPPB protein contains 2 main functional domains: a nucleotidyl transferase domain and a bacterial transferase hexapeptide domain. Carss et al. (2013) determined that the GMPPB gene is transcribed as 2 isoforms in human tissues. The longer isoform (GenBank NM_021971.1) was strongly expressed in all fetal and adult tissues tested, including brain and skeletal muscle, whereas the shorter isoform (GenBank NM_013334.2) was weakly expressed in the tissues tested. There appeared to be no developmental difference in the expression of the 2 isoforms. </p><p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2001) obtained a clone, which they designated KIAA1851, containing 2 coding regions separated by 2.4 kb. They identified the upstream coding region as that of GMPPB and suggested that KIAA1851 may represent a read-through transcript of the GMPPB gene. Hartz (2014) determined that the KIAA1851 sequence (GenBank AB058754) includes the sequence of AMIGO3 (615691) (GenBank AY237003) in addition to that of GMPPB. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The coding DNA sequence of one isoform of the GMPPB gene (GenBank NM_021971.1) contains 10 exons, whereas that of another isoform (GenBank NM_013334.2) contains 8 exons (Carss et al., 2013). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hartz (2013) mapped the GMPPB gene to chromosome 3p21.31 based on an alignment of the GMPPB sequence (GenBank AB058754) with the genomic sequence (GRCh37).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ning and Elbein (2000) found that recombinant porcine Gmpp-beta catalyzed bidirectional conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose. Compared with purified pig liver Gmpp, which was a dimer of alpha and beta subunits, recombinant Gmpp-beta showed much lower activity as a GDP-glucose pyrophosphorylase (EC 2.7.7.34). Divalent cations, particularly Mn(2+), enhanced the Gmpp-beta reaction, whereas Mg(2+) was the preferred cofactor for the endogenous dimeric enzyme. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing combined with Sanger sequencing of 8 unrelated patients with various forms of congenital muscular dystrophy, Carss et al. (2013) identified 8 different mutations in the GMPPB gene (GenBank NM_02197.1) (615320.0001-615320.0008). All mutations occurred in homozygous or compound heterozygous state and segregated with the disorder in the families in whom parental DNA was available. All affected individuals had at least 1 mutation affecting the highly conserved nucleotidyl transferase domain. The phenotype was highly variable. The most severely affected patient had muscle weakness at birth with severely delayed psychomotor development, retinal dysfunction, and pontocerebellar hypoplasia, reminiscent of muscle-eye-brain disease and consistent with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; 615350). Four patients presented with a slightly milder phenotype with onset of muscle weakness in the first months of life with milder intellectual disability with or without cerebellar hypoplasia, consistent with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual disability type B14 (MDDGB14; 615351). The least severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352), also known as LGMDR19 and LGMD2T, was present in 3 unrelated patients, 1 of whom had onset at age 4 and normal intellectual function. Variable features seen in some patients included microcephaly, seizures, cataracts, and cardiac dysfunction. All patients had dystrophic features on muscle biopsy, and immunohistochemical and flow cytometric analysis of patient cells showed reduced glycosylation of alpha-dystroglycan. Overexpression of wildtype GMPPB in fibroblasts from an affected individual partially restored glycosylation of DAG1. Whereas wildtype GMPPB localized to the cytoplasm, 5 of the identified missense mutations caused formation of aggregates in the cytoplasm or near membrane protrusions. Knockdown of the GMPPB ortholog in zebrafish caused structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of DAG1. None of the patients had evidence of abnormal serum transferrin glycoforms. </p><p>In 7 patients from 5 unrelated families with MDDGC14 with features of congenital myasthenic syndrome, Belaya et al. (2015) identified homozygous or compound heterozygous mutations in the GMPPB gene (see, e.g., 615320.0007; 615320.0009-615320.0011). The mutations in the first patient were found by whole-exome sequencing; mutations in subsequent patients were found by screening of the GMPPB gene in a cohort of patients diagnosed with congenital myasthenic syndrome. The patients with GMPPB mutations showed decrement of compound muscle action potentials on repetitive nerve stimulation as well as myopathic findings on muscle biopsy and increased serum creating kinase. The findings indicated that GMPPB mutations can lead to a wide spectrum of clinical features including defects in neuromuscular transmission. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Carss et al. (2013) found that zebrafish gmppb is expressed throughout development. Morpholino knockdown of gmppb in zebrafish resulted in smaller embryos with multiple anomalies, including bent tails, hypopigmentation, microphthalmia, hydrocephalus, and reduced motility. Muscle fibers in mutant zebrafish were sparse and disorganized, and the myosepta were damaged or incompletely developed. There was also evidence of sarcolemmal damage. Immunostaining showed defective glycosylation of DAG1 associated with abnormal structure of the basement membrane. These findings were reminiscent of the muscular dystrophy phenotype found in humans with GMPPB mutations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GMPPB, ASP334ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397509422,
|
|
|
|
|
|
gnomAD: rs397509422,
|
|
|
|
|
|
ClinVar: RCV000054432, RCV000054433, RCV000256412, RCV000651273, RCV000788090, RCV001836725, RCV002513710, RCV004549480
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (P1) with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; 615350), Carss et al. (2013) identified compound heterozygous mutations in the GMPPB gene: a c.1000G-A transition resulting in an asp334-to-asn (D334N) substitution at a highly conserved residue at the C terminus, and a c.220C-T transition resulting in an arg74-to-ter (R74X; 615320.0002) substitution. The mutations were identified by exome sequencing and confirmed by Sanger sequencing. Each unaffected parent was heterozygous for 1 of the mutations. Transfection of the D334N mutation into myoblasts caused the protein to form cytoplasmic aggregates. The R74X mutation, which occurs in the nucleotidyl transferase domain, is predicted to cause a severely truncated protein and nonsense-mediated mRNA. The patient had severely delayed psychomotor development, sensorineural hearing loss, retinal dysfunction, and pontine and cerebellar hypoplasia on brain MRI. Studies of the patient's skeletal muscle and fibroblasts showed decreased glycosylation of alpha-dystroglycan (DAG1; 128239), which was partially restored by transfection of wildtype GMPPB. An unrelated patient (P2) with a somewhat less severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) with mental retardation, was found to be compound heterozygous for D334N and a c.64C-T transition resulting in a pro22-to-ser (P22S; 615320.0003) substitution at a highly conserved residue in the nucleotidyl transferase domain. Transfection of the P22S mutation into myoblasts caused the protein to aggregate near membrane protrusions into the cytoplasm. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GMPPB, ARG74TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397509423,
|
|
|
|
|
|
|
|
ClinVar: RCV000054434
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg74-to-ter (R74X) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 (MDDGA14; 615350) by Carss et al. (2013), see 615320.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GMPPB, PRO22SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397509424,
|
|
|
|
|
|
|
|
ClinVar: RCV000054435
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro22-to-ser (P22S) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) by Carss et al. (2013), see 615320.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GMPPB, ARG185CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397509425,
|
|
|
|
|
|
gnomAD: rs397509425,
|
|
|
|
|
|
ClinVar: RCV000054436, RCV000054437, RCV000200261, RCV000503216, RCV000623944, RCV001781385
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Mexican patients (P3 and P4) with congenital muscular dystrophy-dystroglycanopathy with mental retardation type B14 (MDDGB14; 615351), Carss et al. (2013) identified a homozygous c.553C-T transition in the GMPPB gene, resulting in an arg185-to-cys (R185C) substitution at a highly conserved residue in the nucleotidyl transferase domain. The mutations were found in 1 of the patients by exome sequencing and confirmed in both patients by Sanger sequencing. The unaffected mother of 1 of the patients was heterozygous for the mutation. Exome sequencing of an Egyptian patient (P8) with a somewhat less severe phenotype, limb-girdle muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) with mental retardation and cardiorespiratory dysfunction, also yielded a homozygous R185C mutation. The unaffected parents of this patient were heterozygous for the mutation. Transfection of the R185C mutation into myoblasts caused the protein to remain evenly distributed in the cytoplasm and had no discernible changes compared to wildtype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GMPPB, PRO32LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397509426,
|
|
|
|
|
|
gnomAD: rs397509426,
|
|
|
|
|
|
ClinVar: RCV000054438, RCV000209926, RCV000493576, RCV000684892
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Italian girls (P5 and P6) with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development type B14 (MDDGB14; 615351), previously reported by Messina et al. (2009), Carss et al. (2013) identified compound heterozygosity for 2 mutations in the GMPPB gene: a c.95C-T transition resulting in a pro32-to-leu (P32L) substitution at a highly conserved residue in the nucleotidyl transferase domain, and a c.860G-A transition resulting in an arg287-to-gln (R287Q; 615320.0006) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. P32L had not been reported, and R287Q is rare and has a minor allele frequency of less than or equal to 0.001 in database controls. Transfection of both mutations into myoblasts caused the protein to form aggregates within the cytoplasm. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 14</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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GMPPB, ARG287GLN
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<br />
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SNP: rs202160208,
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gnomAD: rs202160208,
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ClinVar: RCV000054439, RCV000209893, RCV000520160, RCV000553832, RCV001266808, RCV001542745, RCV001814035, RCV003407434
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the arg287-to-gln (R287Q) mutation in the GMPPB gene that was found in compound heterozygous state in 2 patients with congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development type B14 (MDDGB14; 615351) by Carss et al. (2013), see 615320.0005. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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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GMPPB, ASP27HIS
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<br />
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SNP: rs142336618,
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gnomAD: rs142336618,
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ClinVar: RCV000054440, RCV000444697, RCV000533184, RCV000610921, RCV001331794, RCV002513711, RCV003388824, RCV003421962
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 6-year-old English boy (P7) with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) without mental retardation, Carss et al. (2013) identified compound heterozygous mutations in the GMPPB gene: a c.79G-C transversion, resulting in an asp27-to-his (D27H) substitution at a highly conserved residue in the nucleotidyl transferase domain, and a c.988G-A transition, resulting in a val330-to-ile (V330I; 615320.0008) substitution at a highly conserved residue in the C terminus. Each unaffected parent was heterozygous for 1 of the mutations. Both variants are rare, with minor allele frequencies of less than or equal to 0.001 in database controls. Transfection of the D27H mutation into myoblasts caused the protein to remain evenly distributed in the cytoplasm and had no discernible changes compared to wildtype, whereas transfection of V330I caused the protein to form aggregates within the cytoplasm. The patient had a mild form of the disorder, presenting only with exercise intolerance at age 4 years. </p><p>For discussion of the D27H mutation (c.79G-C, NM_021971) in the GMPPB gene that was found in compound heterozygous state in patients with MDDGC14 with features of congenital myasthenic syndrome by Belaya et al. (2015), see 615320.0009 and 615320.0010. Belaya et al. (2015) found the D27H mutation at a low frequency (0.077%) in the Exome Variant Server database. D27H mutant protein expression was decreased compared to wildtype in transfected HEK293 cells. </p><p>NM_021971</p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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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GMPPB, VAL330ILE
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<br />
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SNP: rs199922550,
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gnomAD: rs199922550,
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ClinVar: RCV000054441, RCV000440664, RCV000501778, RCV000623470, RCV000651278, RCV001330455
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the val330-to-ile (V330I) mutation in the GMPPB gene that was found in compound heterozygous state in a patient with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) without mental retardation by Carss et al. (2013), see 615320.0007. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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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GMPPB, ARG287TRP
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<br />
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SNP: rs142908436,
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gnomAD: rs142908436,
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ClinVar: RCV000211126, RCV000609930, RCV000698947, RCV001508147
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 48-year-old woman with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) with features of congenital myasthenic syndrome, Belaya et al. (2015) identified compound heterozygous mutations in the GMPPB gene: a c.859C-T transition (c.859C-T, NM_021971), resulting in an arg287-to-trp (R287W) substitution, and D27H (615320.0007). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Both mutations were found at low frequencies in the Exome Variant Server database (0.077% for D27H and 0.008% for R287W). In transfected HEK293 cells, R287W protein expression was undetectable, whereas D27H expression was decreased compared to wildtype. In a transfected mouse muscle cell line, R287W mutant protein expression was drastically reduced, and the protein that was expressed displayed a punctate pattern of localization, suggesting abnormal protein aggregation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0010 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</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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GMPPB, VAL254MET
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<br />
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SNP: rs875989850,
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gnomAD: rs875989850,
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ClinVar: RCV000211128, RCV000430158, RCV002515608
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 28-year-old woman with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) with features of congenital myasthenic syndrome, Belaya et al. (2015) identified compound heterozygous mutations in the GMPPB gene: a c.760G-A transition (c.760G-A, NM_021971), resulting in a val254-to-met (V254M) substitution at a conserved residue and D27H (615320.0007). The mutations segregated with the disorder in the family. In transfected HEK293 cells, V254M protein expression was undetectable, whereas D27H expression was decreased compared to wildtype. In a transfected mouse muscle cell line, V254M mutant protein expression was drastically reduced, and the protein that was expressed displayed a punctate pattern of localization, suggesting abnormal protein aggregation. </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>.0011 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
|
|
GMPPB, PRO103LEU
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<br />
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SNP: rs875989851,
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gnomAD: rs875989851,
|
|
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|
|
ClinVar: RCV000211125, RCV001814120
|
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 adult sibs, born of consanguineous Iranian parents, with muscular dystrophy-dystroglycanopathy type C14 (MDDGC14; 615352) with features of a congenital myasthenic syndrome, Belaya et al. (2015) identified a homozygous c.308C-T transition (c.308C-T, NM_021971) in the GMPPB gene, resulting in a pro103-to-leu (P103L) substitution at a conserved residue in the nucleotidyl transferase domain. The mutation segregated with the disorder in the family. In transfected HEK293 cells, P103L protein expression was slightly decreased compared to wildtype. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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|
</span>
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|
</h4>
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<div>
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<p />
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|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Belaya, K., Rodriguez Cruz, P. M., Liu, W. W., Maxwell, S., McGowan, S., Farrugia, M. E., Petty, R., Walls, T. J., Sedghi, M., Basiri, K., Yue, W. W., Sarkozy, A., and 10 others.
|
|
<strong>Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.</strong>
|
|
Brain 138: 2493-2504, 2015.
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[PubMed: 26133662]
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[Full Text: https://doi.org/10.1093/brain/awv185]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Carss, K. J., Stevens, E., Foley, A. R., Cirak, S., Riemersma, M., Torelli, S., Hoischen, A., Willer, T., van Scherpenzeel, M., Moore, S. A., Messina, S., Bertini, E., and 24 others.
|
|
<strong>Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan.</strong>
|
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Am. J. Hum. Genet. 93: 29-41, 2013.
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[PubMed: 23768512]
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[Full Text: https://doi.org/10.1016/j.ajhg.2013.05.009]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 7/19/2013.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 3/12/2014.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Messina, S., Tortorella, G., Concolino, D., Spano, M., D'Amico, A., Bruno, C., Santorelli, F. M., Mercuri, E., Bertini, E.
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<strong>Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy.</strong>
|
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Neurology 73: 1599-1601, 2009.
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[PubMed: 19901254]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181c0d47a]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Nagase, T., Nakayama, M., Nakajima, D., Kikuno, R., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 8: 85-95, 2001.
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[PubMed: 11347906]
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[Full Text: https://doi.org/10.1093/dnares/8.2.85]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ning, B., Elbein, A. D.
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<strong>Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase: evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins.</strong>
|
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Europ. J. Biochem. 267: 6866-6874, 2000.
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[PubMed: 11082198]
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[Full Text: https://doi.org/10.1046/j.1432-1033.2000.01781.x]
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</p>
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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 class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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 : 5/11/2016<br>Patricia A. Hartz - updated : 3/12/2014<br>Cassandra L. Kniffin - updated : 7/31/2013
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</span>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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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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Patricia A. Hartz : 7/19/2013
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<span class="text-nowrap mim-text-font">
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Edit History:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/19/2020<br>carol : 09/25/2018<br>alopez : 05/13/2016<br>ckniffin : 5/11/2016<br>alopez : 7/22/2015<br>mcolton : 7/21/2015<br>carol : 10/20/2014<br>mcolton : 10/15/2014<br>carol : 10/3/2014<br>mgross : 3/12/2014<br>mcolton : 3/12/2014<br>carol : 10/7/2013<br>carol : 8/8/2013<br>carol : 8/6/2013<br>carol : 8/6/2013<br>ckniffin : 7/31/2013<br>mgross : 7/19/2013
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NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
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and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
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medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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