5294 lines
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Entry
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- *606596 - FUKUTIN-RELATED PROTEIN; FKRP
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- OMIM
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<p>
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<span class="h4">*606596</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606596">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div 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 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 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="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=ENSG00000181027;t=ENST00000318584" 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=79147" 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=606596" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000181027;t=ENST00000318584" 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_001039885,NM_024301,XM_005259247,XM_005259248,XM_005259249,XM_011527306,XM_011527307,XM_017027297,XM_024451707,XM_047439421,XM_047439422,XM_047439423,XM_047439424,XM_047439425,XM_047439426,XM_047439427,XM_047439428,XM_047439429" 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_024301" 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=606596" 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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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05962&isoform_id=05962_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/FKRP" 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/10434145,12803561,13236528,15866720,40034237,46395992,89941475,119577848,119577849,158256000,193787868,530417230,530417232,530417234,768011050,768011054,1034609464,1370475934,2217323068,2217323070,2217323075,2217323077,2217323079,2217323081,2217323083,2217323085,2217323090,2462567657,2462567659,2462567661,2462567663,2462567665,2462567667,2462567669,2462567671,2462567673,2462567675,2462567677,2462567679,2462567681,2462567683,2462567685" 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/Q9H9S5" 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=79147" 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=ENSG00000181027;t=ENST00000318584" 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=FKRP" 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=FKRP" 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+79147" 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/FKRP" 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:79147" 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/79147" 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=chr19&hgg_gene=ENST00000318584.10&hgg_start=46744760&hgg_end=46758575&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:17997" 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=606596[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=606596[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/FKRP/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/ENSG00000181027" 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=FKRP" 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=FKRP" 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=FKRP" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/FKRP" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FKRP&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/PA134976709" 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:17997" 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/FBgn0034567.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:2447586" 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/FKRP#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:2447586" 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/79147/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=79147" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070412-4" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
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</a>
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:79147" 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=FKRP&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> 718180000<br />
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<strong>ICD10CM:</strong> G71.038<br />
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">ICD+</a>
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</div>
|
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
606596
|
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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>
|
|
<h3>
|
|
<span class="mim-font">
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FUKUTIN-RELATED PROTEIN; FKRP
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FKRP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FKRP</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">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/859?start=-3&limit=10&highlight=859">19q13.32</a>
|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:46744760-46758575&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'})">19:46,744,760-46,758,575</a> </span>
|
|
</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>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=613153,606612,607155" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/859?start=-3&limit=10&highlight=859">
|
|
19q13.32
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613153"> 613153 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
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|
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|
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|
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</tr>
|
|
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|
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with or without impaired intellectual development), type B, 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/606612"> 606612 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/607155"> 607155 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p><a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> identified the fukutin-related protein gene (FKRP) by database screening with the mouse fukutin sequence as query. The human version of the sequence was determined by a combination of EST assembly, RT-PCR, and RACE. The cDNA encodes a deduced 495-amino acid protein. Sequence analysis predicted a molecular organization similar to that found in several Golgi-resident glycosyltransferases. Northern blot analysis detected a 4.0-kb FKRP transcript expressed predominantly in skeletal muscle, placenta, and heart, and relatively weakly in other tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using transfection experiments, <a href="#10" class="mim-tip-reference" title="Esapa, C. T., Benson, M. A., Schroder, J. E., Martin-Rendon, E., Brockington, M., Brown, S. C., Muntoni, F., Kroger, S., Blake, D. J. <strong>Functional requirements for fukutin-related protein in the Golgi apparatus.</strong> Hum. Molec. Genet. 11: 3319-3331, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471058</a>] [<a href="https://doi.org/10.1093/hmg/11.26.3319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471058">Esapa et al. (2002)</a> determined that FKRP and fukutin (FKTN; <a href="/entry/607440">607440</a>) are targeted to the medial Golgi apparatus through their N termini and transmembrane domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12471058" 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="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> determined that the 12-kb FKRP gene is composed of 3 noncoding exons and a single large exon of 3.8 kb that contains part of the 5-prime untranslated region (UTR) and the entire open reading frame (ORF) and 3-prime UTR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" 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 radiation hybrid analysis, <a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> localized the FKRP gene to chromosome 19q13.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" 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>Mutation in the FKRP gene can cause 3 different forms of muscular dystrophy-dystroglycanopathy (MDDG): a severe congenital form with brain and eye anomalies (type A5; MDDGA5; <a href="/entry/613153">613153</a>), formerly designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB); a less severe congenital form with or without impaired intellectual development (type B5; MDDGB5; <a href="/entry/606612">606612</a>); and a milder limb-girdle form (type C5; MDDGC5; <a href="/entry/607155">607155</a>), also known as LGMDR9 and LGMD2I.</p><p>In 7 families with a distinct form of congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>), <a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> identified 11 different mutations in the FKRP gene (see, e.g., <a href="#0001">606596.0001</a>-<a href="#0003">606596.0003</a>). Nine were missense mutations and 2 were nonsense mutations. In 4 families, the affected individuals were compound heterozygotes; in the other 3, the patients were homozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" 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 17 of 25 families with limb-girdle muscular dystrophy (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#5" class="mim-tip-reference" title="Brockington, M., Yuva, Y., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Herrmann, R., Anderson, L. V. B., Bashir, R., Burgunder, J.-M., Fallet, S., Romero, N., and 10 others. <strong>Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.</strong> Hum. Molec. Genet. 10: 2851-2859, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741828</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741828">Brockington et al. (2001)</a> found mutations in the FKRP gene. Affected individuals from 15 of 17 families had an identical L276I mutation (<a href="#0004">606596.0004</a>); individuals in 5 families were homozygous for this mutation. Linkage analysis identified at least 2 possible haplotypes in linkage disequilibrium with this mutation. Patients with the L276I change had the clinically less severe phenotype, suggesting that this is a less disruptive FKRP mutation than those found in MDDGB5. A variable reduction of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) expression was observed in the skeletal muscle biopsy of all individuals studied. In addition, several cases showed a deficiency of laminin-2 (LAMA2; <a href="/entry/156225">156225</a>) either by immunocytochemistry or Western blotting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Esapa, C. T., Benson, M. A., Schroder, J. E., Martin-Rendon, E., Brockington, M., Brown, S. C., Muntoni, F., Kroger, S., Blake, D. J. <strong>Functional requirements for fukutin-related protein in the Golgi apparatus.</strong> Hum. Molec. Genet. 11: 3319-3331, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471058</a>] [<a href="https://doi.org/10.1093/hmg/11.26.3319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471058">Esapa et al. (2002)</a> found that overexpression of FKRP in CHO cells altered the posttranslational processing of alpha- and beta-dystroglycan, thus inhibiting maturation of the 2 isoforms. Mutations in the DxD motif or in the Golgi-targeting sequence, which cause inefficient trafficking of FKRP to the Golgi apparatus, did not alter dystroglycan processing in vitro. The P448L mutation in FKRP (<a href="#0003">606596.0003</a>) resulted in mislocalization of the mutant protein and disruption in dystroglycan processing. <a href="#10" class="mim-tip-reference" title="Esapa, C. T., Benson, M. A., Schroder, J. E., Martin-Rendon, E., Brockington, M., Brown, S. C., Muntoni, F., Kroger, S., Blake, D. J. <strong>Functional requirements for fukutin-related protein in the Golgi apparatus.</strong> Hum. Molec. Genet. 11: 3319-3331, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471058</a>] [<a href="https://doi.org/10.1093/hmg/11.26.3319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471058">Esapa et al. (2002)</a> concluded that FKRP is required for the posttranslational modification of dystroglycan. They suggested that aberrant processing of dystroglycan caused by a mislocalized FKRP mutant could be a novel mechanism that causes congenital muscular dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12471058" 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 16 patients with LGMD (MDDGC5; <a href="/entry/607155">607155</a>) from 13 Brazilian families, <a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">de Paula et al. (2003)</a> identified 10 distinct mutations, including 9 novel mutations, in the FKRP gene (see, e.g., <a href="#0012">606596.0012</a>-<a href="#0015">606596.0015</a>). The most common mutation, L276I (<a href="#0004">606596.0004</a>), was identified in 9 of 26 alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., Voit, T., Longman, C., Steinbrecher, A., Straub, V., Yuva, Y., Herrmann, R., Sperner, J., Korenke, C., Diesen, C., Dobyns, W. B., Brunner, H. G., van Bokhoven, H., Brockington, M., Muntoni, F. <strong>Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome.</strong> J. Med. Genet. 41: e61, 2004. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121789</a>] [<a href="https://doi.org/10.1136/jmg.2003.013870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15121789">Beltran-Valero de Bernabe et al. (2004)</a> identified homozygous mutations in the FKRP gene (Y307N, <a href="#0016">606596.0016</a> and C318Y, <a href="#0017">606596.0017</a>) in 2 unrelated patients with muscle-eye-brain disease and Walker-Warburg syndrome (MDDGA5; <a href="/entry/613153">613153</a>), respectively. Both disorders are characterized by severe disruption of brain and eye structure in addition to muscular dystrophy. The findings expanded the phenotypic spectrum of disorders associated with mutation in the FKRP gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Mercuri, E., Messina, S., Bruno, C., Mora, M., Pegoraro, E., Comi, G. P., D'Amico, A., Aiello, C., Biancheri, R., Berardinelli, A., Boffi, P., Cassandrini, D. <strong>Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.</strong> Neurology 72: 1802-1809, 2009. Note: Erratum: Neurology 93: 371 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19299310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19299310</a>] [<a href="https://doi.org/10.1212/01.wnl.0000346518.68110.60" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19299310">Mercuri et al. (2009)</a> identified FKRP mutations in 7 (9%) of 81 Italian patients with a dystroglycanopathy. Three had MEB and 4 had a less severe congenital muscular dystrophy. Three patients had normal brain MRI. In general, the more severe phenotypes appeared to be associated with mutations predicted to result in severe disruption of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19299310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In transfected COS-7 cells, <a href="#11" class="mim-tip-reference" title="Esapa, C. T., McIlhinney, R. A. J., Blake, D. J. <strong>Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells.</strong> Hum. Molec. Genet. 14: 295-305, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15574464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15574464</a>] [<a href="https://doi.org/10.1093/hmg/ddi026" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15574464">Esapa et al. (2005)</a> showed that FKRP mutants, which are associated with the more severe disease phenotypes (S221R, <a href="#0008">606596.0008</a>; A455D, <a href="#0009">606596.0009</a>; P448L, <a href="#0003">606596.0003</a>) were retained in the endoplasmic reticulum (ER), whereas the wildtype protein and the mutant L276I (<a href="#0004">606596.0004</a>) that causes LGMD (MDDGC5) were found predominantly in the Golgi apparatus. The ER-retained proteins had a shorter half-life than the wildtype FKRP and were preferentially degraded by the proteasome. Furthermore, calnexin (CANX; <a href="/entry/114217">114217</a>) bound preferentially to the ER-retained mutants, suggesting that it may participate in the quality control pathway for FKRP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15574464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Sveen, M.-L., Schwartz, M., Vissing, J. <strong>High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark.</strong> Ann. Neurol. 59: 808-815, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16634037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16634037</a>] [<a href="https://doi.org/10.1002/ana.20824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16634037">Sveen et al. (2006)</a> identified FKRP mutations in 38 of 99 Danish individuals with a clinical diagnosis of limb-girdle muscular dystrophy. Of the 38 individuals, 27 were homozygous for L276I, and 11 were compound heterozygous for L276I and another pathogenic FKRP mutation. The homozygous patients had later onset, milder clinical progression, and less muscle weakness compared to compound heterozygous patients, all of whom were wheelchair-bound by their mid-twenties. Cardiac and respiratory involvement was found in both groups. Nine L276I homozygous, but no compound heterozygous, patients had initial symptoms of exertional myoglobinuria. The L276I variant was identified in 1 of 200 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16634037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a retrospective review of brain MRI in patients with FKRP mutations, <a href="#21" class="mim-tip-reference" title="Mercuri, E., Topaloglu, H., Brockington, M., Berardinelli, A., Pichiecchio, A., Santorelli, F., Rutherford, M., Talim, B., Ricci, E., Voit, T., Muntoni, F. <strong>Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.</strong> Arch. Neurol. 63: 251-257, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16476814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16476814</a>] [<a href="https://doi.org/10.1001/archneur.63.2.251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16476814">Mercuri et al. (2006)</a> found a range of various patterns. Five of 13 patients had normal imaging results and normal neurologic function. Three patients had isolated cerebellar cysts and mental retardation without other abnormal brain structure. Of the 5 remaining patients, 2 had features of muscle-eye-brain disease, 1 had features of Walker-Warburg syndrome, and 2 had cerebellar cysts with nodular heterotopia and cerebellar dysplasia, respectively. There was no correlation with severity of the neurologic involvement and FKRP mutation. <a href="#21" class="mim-tip-reference" title="Mercuri, E., Topaloglu, H., Brockington, M., Berardinelli, A., Pichiecchio, A., Santorelli, F., Rutherford, M., Talim, B., Ricci, E., Voit, T., Muntoni, F. <strong>Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.</strong> Arch. Neurol. 63: 251-257, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16476814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16476814</a>] [<a href="https://doi.org/10.1001/archneur.63.2.251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16476814">Mercuri et al. (2006)</a> postulated that the variability may be related to the severity of disruption of alpha-dystroglycan glycosylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16476814" 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="#1" class="mim-tip-reference" title="Ackroyd, M. R., Skordis, L., Kaluarachchi, M., Godwin, J., Prior, S., Fidanboylu, M., Piercy, R. J., Muntoni, F., Brown, S. C. <strong>Reduced expression of fukutin related protein in mice results in a model for fukutin related protein associated muscular dystrophies.</strong> Brain 132: 439-451, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19155270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19155270</a>] [<a href="https://doi.org/10.1093/brain/awn335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19155270">Ackroyd et al. (2009)</a> found that mice with a homozygous knockin Y307N (<a href="#0016">606596.0016</a>) mutation in the Fkrp showed no distinguishable phenotype from wildtype mice up to 6 months of age. Fkrp transcript levels were similar to controls. However, mice homozygous for the Y307N mutation and a neomycin cassette in intron 2 of the Fkrp gene died soon after birth. These mice showed a reduction of alpha-dystroglycan in muscle, eye and brain, and had reduced levels of Fkrp transcript (about 40% of control values). The phenotype was consistent with muscle-eye-brain disease in humans; mutant mice showed decreased muscle mass, perturbation of the limiting membrane of the eye, and a disturbance in neuronal migration. The results suggested that the generation of a mouse model for FKRP-related muscular dystrophy requires a knockdown hypomorph Fkrp allele rather than a knockin missense mutation in order to give rise to a disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19155270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Kawahara, G., Guyon, J. R., Nakamura, Y., Kunkel, L. M. <strong>Zebrafish models for human FKRP muscular dystrophies.</strong> Hum. Molec. Genet. 19: 623-633, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp528" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19955119">Kawahara et al. (2010)</a> reported that downregulating fkrp expression in zebrafish by 2 different morpholinos resulted in embryos that had developmental defects similar to those observed in human muscular dystrophies associated with human FKRP mutations. The fkrp morphants showed phenotypes involving alterations in somitic structure and muscle fiber organization, as well as defects in developing eye morphology. Additionally, they were found to have a reduction in alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) glycosylation and a shortened myofiber length. Coinjection of fish or human FKRP mRNA along with the morpholino restored normal development, alpha-dystroglycan glycosylation, and laminin- binding activity of alpha-dystroglycan in the morphants. Coinjection of the human FKRP mRNA containing mutations causative of human disorders could not significantly restore their phenotypes. Morphant zebrafish harboring human FKRP mutations showed a wide phenotypic range, similar to that seen in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19955119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Chan, Y. M., Keramaris-Vrantsis, E., Lidov, H. G., Norton, J. H., Zinchenko, N., Gruber, H. E., Thresher, R., Blake, D. J., Ashar, J., Rosenfeld, J., Lu, Q. L. <strong>Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies.</strong> Hum. Molec. Genet. 19: 3995-4006, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20675713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20675713</a>] [<a href="https://doi.org/10.1093/hmg/ddq314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20675713">Chan et al. (2010)</a> generated a transgenic mouse model with a P448L Fkrp mutation (<a href="#0003">606596.0003</a>) and a neomycin cassette. About one-third of homozygous P448L mice died at birth or within 2 days. The remaining mice recapitulated the features of FKRP-associated muscular dystrophy, including muscle weakness, dystrophic pathology in skeletal muscles, increased serum creatine kinase, and eye and brain abnormalities, such as hydrocephalus and abnormal neuronal migration. Biochemical analysis showed that alpha-DAG was not functionally glycosylated. In another mouse model, homozygous deletion of the C-terminal consensus DxD motif (E310del/E310del) resulted in early embryonic lethality. Only a few compound heterozygous mice (P448L/E310del) were born, and they died at birth. The findings confirmed a critical role of FKRP in posttranslational modification of alpha-DAG. In a follow-up to the study of <a href="#6" class="mim-tip-reference" title="Chan, Y. M., Keramaris-Vrantsis, E., Lidov, H. G., Norton, J. H., Zinchenko, N., Gruber, H. E., Thresher, R., Blake, D. J., Ashar, J., Rosenfeld, J., Lu, Q. L. <strong>Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies.</strong> Hum. Molec. Genet. 19: 3995-4006, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20675713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20675713</a>] [<a href="https://doi.org/10.1093/hmg/ddq314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20675713">Chan et al. (2010)</a>, <a href="#3" class="mim-tip-reference" title="Blaeser, A., Keramaris, E., Chan, Y. M., Sparks, S., Cowley, D., Xiao, X., Lu, Q. L. <strong>Mouse models of fukutin-related protein mutations show a wide range of disease phenotypes.</strong> Hum. Genet. 132: 923-934, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23591631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23591631</a>] [<a href="https://doi.org/10.1007/s00439-013-1302-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23591631">Blaeser et al. (2013)</a> generated several mouse models carrying different combinations of mutations in the Fkrp gene, including P448L, E310del, and L276I (<a href="#0004">606596.0004</a>). One surviving mouse that was compound heterozygous for P448L/E310del showed a severe dystrophic phenotype, with muscle degeneration, hydrocephalus, and abnormal migration of neurons in the cerebral cortex and cerebellum. In contrast, most of the L276I/P448L or L276I/E310del compound heterozygous mice were normal, but some showed later onset of mild muscle weakness associated with increased serum creatine kinase and mild muscular dystrophy without brain abnormalities. Skeletal muscle from these mutant mice showed less severe decreases in Fkrp expression and higher amounts of functional glycosylated DAG compared to P448L/E310del, P448L/P448L, and E310del/E310del mice. Removal of the neomycin cassette from the mutant alleles resulted in increased Fkrp levels and attenuated the phenotypes in all mutants. The findings indicated that L276I can provide sufficient activity to avoid neurologic defects, suggesting that different missense mutations affect the function of FKRP, resulting in phenotypic variability. The wide range of disease phenotypes observed in these mice recapitulated the variable phenotypic severity observed in humans with different FKRP mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20675713+23591631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606596[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs104894679 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894679;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/rs104894679?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=rs104894679" 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=rs104894679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#20" class="mim-tip-reference" title="Mercuri, E., Sewry, C. A., Brown, S. C., Brockington, M., Jungbluth, H., DeVile, C., Counsell, S., Manzur, A., Muntoni, F. <strong>Congenital muscular dystrophy with secondary merosin deficiency and normal brain MRI: a novel entity?</strong> Neuropediatrics 31: 186-189, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11071142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11071142</a>] [<a href="https://doi.org/10.1055/s-2000-7460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11071142">Mercuri et al. (2000)</a> described the clinical features of 2 sibs in a Scottish family who appeared to be affected by a novel form of congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>). Both children presented soon after birth with hypotonia and feeding difficulties. They never acquired the ability to walk because of severe weakness, which also affected their facial muscles. Weakness was greater in the arms than legs, with prominent wasting of the deltoids and pectoral muscles, whereas both calf and quadriceps muscles were hypertrophied. Cognitive development, intelligence, and vision were normal, as was brain MRI. Serum creatine kinase was markedly elevated. The older sib died suddenly at age 7 years, following an upper respiratory tract infection. <a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> found that these affected sibs were compound heterozygotes for mutations in the FKRP gene: tyr309-to-cys (Y309C) and ser385-to-ter (S385X; <a href="#0002">606596.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11592034+11071142" 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>.0002 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs104894680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894680;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/rs104894680?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=rs104894680" 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=rs104894680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the ser385-to-ter (S385X) mutation in the FKRP gene that was found in compound heterozygous state in patients with a form of congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>) by <a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a>, see <a href="#0001">606596.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" 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 (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs104894681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894681;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/rs104894681?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=rs104894681" 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=rs104894681" 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 consanguineous family from Libya with a severe form of congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>), <a href="#4" class="mim-tip-reference" title="Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F. <strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong> Am. J. Hum. Genet. 69: 1198-1209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592034">Brockington et al. (2001)</a> found that the 1 affected child was homozygous for a pro448-to-leu (P448L) missense mutation in the FKRP gene. The patient presented in the first few weeks of life with hypotonia and feeding difficulties, followed by motor delay. On examination at age 16 months, she could not walk and was weaker in her arms than in her legs. She had calf hypertrophy and facial weakness. Serum creatine kinase was very high, and she had a myopathic EMG. Her intelligence was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592034" 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 (LIMB-GIRDLE), TYPE C, 5</strong>
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FKRP, LEU276ILE (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937900;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937900</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937900;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/rs28937900?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=rs28937900" 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=rs28937900" 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=RCV000004442 OR RCV000082182 OR RCV000226653 OR RCV000231711 OR RCV000503787 OR RCV000612115 OR RCV000626960 OR RCV000660622 OR RCV001197775 OR RCV001329320 OR RCV001526640 OR RCV002222338 OR RCV002408451 OR RCV003993736 OR RCV004532287 OR RCV004776425 OR RCV004776426" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004442, RCV000082182, RCV000226653, RCV000231711, RCV000503787, RCV000612115, RCV000626960, RCV000660622, RCV001197775, RCV001329320, RCV001526640, RCV002222338, RCV002408451, RCV003993736, RCV004532287, RCV004776425, RCV004776426" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004442...</a>
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<p>In 15 of 17 families with autosomal recessive limb-girdle muscular dystrophy (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#5" class="mim-tip-reference" title="Brockington, M., Yuva, Y., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Herrmann, R., Anderson, L. V. B., Bashir, R., Burgunder, J.-M., Fallet, S., Romero, N., and 10 others. <strong>Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.</strong> Hum. Molec. Genet. 10: 2851-2859, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741828</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741828">Brockington et al. (2001)</a> found homozygosity or compound heterozygosity for an 826C-A transversion in the FKRP gene, predicted to result in a substitution of isoleucine for leucine 276 (L276I). Patients with the L276I change had the clinically less severe phenotype, suggesting that this is a less disruptive FKRP mutation than those found in patients with MDDGB5; see, e.g., <a href="#0001">606596.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Mercuri, E., Brockington, M., Straub, V., Quijano-Roy, S., Yuva, Y., Herrmann, R., Brown, S. C., Torelli, S., Dubowitz, V., Blake, D. J., Romero, N. B., Estournet, B., Sewry, C. A., Guicheney, P., Voit, T., Muntoni, F. <strong>Phenotypic spectrum associated with mutations in the fukutin-related protein gene.</strong> Ann. Neurol. 53: 537-542, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666124</a>] [<a href="https://doi.org/10.1002/ana.10559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12666124">Mercuri et al. (2003)</a> reported a patient with limb-girdle muscular dystrophy who was compound heterozygous for 2 mutations in the FKRP gene: L276I and Y307N (<a href="#0016">606596.0016</a>). The patient had an unusually severe form of the disorder and died in his early teens. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12666124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">De Paula et al. (2003)</a> identified the L276I mutation in 9 of 26 mutated alleles among 13 Brazilian families with LGMD (MDDGC5). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" 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 affected members of 5 Hutterite families with autosomal recessive LGMD, <a href="#13" class="mim-tip-reference" title="Frosk, P., Greenberg, C. R., Tennese, A. A. P., Lamont, R., Nylen, E., Hirst, C., Frappier, D., Roslin, N. M., Zaik, M., Bushby, K., Straub, V., Zatz, M., de Paula, F., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.</strong> Hum. Mutat. 25: 38-44, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15580560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15580560</a>] [<a href="https://doi.org/10.1002/humu.20110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15580560">Frosk et al. (2005)</a> identified homozygosity for the L276I mutation. A single common haplotype surrounding the FKRP gene was identified in the Hutterite LGMD patients, and an identical core haplotype was also found in 19 other non-Hutterite LGMD patients from Europe, Canada, and Brazil, carrying the L276I mutation. This finding indicated that the L276I dispersed from populations of European origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15580560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R. <strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong> Europ. J. Hum. Genet. 13: 978-982, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15886712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15886712</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201436" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15886712">Frosk et al. (2005)</a> reported a Hutterite family in which 2 boys, aged 7 and 10 years, were homozygous for both the L276I mutation and an LGMD2H (LGMDR8; <a href="/entry/254110">254110</a>)-related TRIM32 mutation (D487N; <a href="/entry/602290#0001">602290.0001</a>). Although they presented at an early age with exercise intolerance and increased serum creatine kinase, the clinical phenotype was not significantly more severe than that of patients with isolated disease. Both parents and 3 other sibs were carriers of the L276I mutation and homozygous for the D487N mutation, with highly variable phenotypic expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15886712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Sveen, M.-L., Schwartz, M., Vissing, J. <strong>High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark.</strong> Ann. Neurol. 59: 808-815, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16634037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16634037</a>] [<a href="https://doi.org/10.1002/ana.20824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16634037">Sveen et al. (2006)</a> identified the L276I mutation in 38 Danish patients with LGMD, of whom 27 were homozygous, and 11 were compound heterozygous with another pathogenic FKRP mutation. The variant was detected in 1 of 200 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16634037" 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>Among 1,127 Schmiedeleut (S-leut) Hutterites from the United States, <a href="#7" class="mim-tip-reference" title="Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. <strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong> Am. J. Hum. Genet. 91: 608-620, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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.2012.08.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22981120">Chong et al. (2012)</a> found 121 heterozygotes and 3 homozygotes for the L276I mutation in the FKRP gene, for a frequency of 0.107, or 1 in 9.5. The carrier frequency in other populations is 1 in 300 (<a href="#13" class="mim-tip-reference" title="Frosk, P., Greenberg, C. R., Tennese, A. A. P., Lamont, R., Nylen, E., Hirst, C., Frappier, D., Roslin, N. M., Zaik, M., Bushby, K., Straub, V., Zatz, M., de Paula, F., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.</strong> Hum. Mutat. 25: 38-44, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15580560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15580560</a>] [<a href="https://doi.org/10.1002/humu.20110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15580560">Frosk et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22981120+15580560" 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>.0005 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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">rs587777823 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777823;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=rs587777823" 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=rs587777823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an individual with early-onset limb-girdle muscular dystrophy (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#5" class="mim-tip-reference" title="Brockington, M., Yuva, Y., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Herrmann, R., Anderson, L. V. B., Bashir, R., Burgunder, J.-M., Fallet, S., Romero, N., and 10 others. <strong>Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.</strong> Hum. Molec. Genet. 10: 2851-2859, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741828</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741828">Brockington et al. (2001)</a>, described compound heterozygosity for mutations in the FKRP gene. One allele contained the recurrent L276I mutation (<a href="#0004">606596.0004</a>), whereas the other allele harbored a 4-bp insertion TACC (390insTACC), which is predicted to generate a premature stop codon at the position of gly132. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741828" 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 (LIMB-GIRDLE), TYPE C, 5</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> rs104894682 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894682;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/rs104894682?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=rs104894682" 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=rs104894682" 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=RCV000004444 OR RCV000471321 OR RCV000501528 OR RCV000725596 OR RCV002222339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004444, RCV000471321, RCV000501528, RCV000725596, RCV002222339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004444...</a>
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<p>In a consanguineous Tunisian family in which 13 members had limb-girdle muscular dystrophy (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#9" class="mim-tip-reference" title="Driss, A., Noguchi, S., Amouri, R., Kefi, M., Sasaki, T., Sugie, K., Souilem, S., Hayashi, Y. K., Shimizu, N., Minoshima, S., Kudoh, J., Hentati, F., Nishino, I. <strong>Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.</strong> Neurology 60: 1341-1344, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707439</a>] [<a href="https://doi.org/10.1212/01.wnl.0000065886.82930.c5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707439">Driss et al. (2003)</a> identified a homozygous 1486T-A change in the FKRP gene, which abolishes a stop codon and is predicted to add 21 amino acids to the C-terminal end of the protein. The patients had symmetric proximal muscle weakness and wasting in all 4 limbs. No heart involvement was found. Immunohistochemical and immunoblot analysis showed abnormal expression of alpha-dystroglycan and alpha-2 laminin, supporting the hypothesis that FKRP has a role in the interaction between components of the extracellular matrix. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707439" 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 (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs28937901 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937901;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/rs28937901?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=rs28937901" 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=rs28937901" 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=RCV000004445 OR RCV000675047 OR RCV003144104 OR RCV003591621" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004445, RCV000675047, RCV003144104, RCV003591621" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004445...</a>
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<p>In a patient with severe merosin-deficient congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>) reported by <a href="#23" class="mim-tip-reference" title="Talim, B., Ferreiro, A., Cormand, B., Vignier, N., Oto, A., Gogus, S., Cila, A., Lehesjoki, A.-E., Pihko, H., Guicheney, P., Topaloglu, H. <strong>Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci.</strong> Neuromusc. Disord. 10: 548-552, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11053680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11053680</a>] [<a href="https://doi.org/10.1016/s0960-8966(00)00140-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11053680">Talim et al. (2000)</a>, <a href="#24" class="mim-tip-reference" title="Topaloglu, H., Brockington, M., Yuva, Y., Talim, B., Haliloglu, G., Blake, D., Torelli, S., Brown, S. C., Muntoni, F. <strong>FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts.</strong> Neurology 60: 988-992, 2003. Note: Erratum: Neurology 60: 1875, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654965</a>] [<a href="https://doi.org/10.1212/01.wnl.0000052996.14099.dc" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654965">Topaloglu et al. (2003)</a> identified a homozygous 946C-A transversion in the FKRP gene, resulting in a pro316-to-thr (P316T) substitution. The patient was from a consanguineous family, and showed hypotonia, muscle weakness, a myopathic face, and high-arched palate by age 1.5 years. She also had lordosis and scoliosis, and was never able to stand or walk. In addition, she had mild mental retardation and multiple small cysts in the cerebellar cortical and subcortical areas of the brain. Also see <a href="#0008">606596.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12654965+11053680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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">rs28937902 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937902;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=rs28937902" 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=rs28937902" 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=RCV000004446 OR RCV003460428" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004446, RCV003460428" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004446...</a>
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<p>In a patient with congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>), <a href="#24" class="mim-tip-reference" title="Topaloglu, H., Brockington, M., Yuva, Y., Talim, B., Haliloglu, G., Blake, D., Torelli, S., Brown, S. C., Muntoni, F. <strong>FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts.</strong> Neurology 60: 988-992, 2003. Note: Erratum: Neurology 60: 1875, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654965</a>] [<a href="https://doi.org/10.1212/01.wnl.0000052996.14099.dc" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654965">Topaloglu et al. (2003)</a> identified a homozygous 663C-A transversion in the FKRP gene, resulting in a ser221-to-arg (S221R) substitution. In addition to the characteristic features of weakness, hypotonia, dystrophic muscle biopsy, and inability to walk, the patient also had mild mental retardation and cerebellar cysts. The authors noted that mental retardation and structural brain changes are not usually part of the clinical spectrum of patients with FKRP mutations, and that these findings may expand the phenotypic spectrum. Also see <a href="#0007">606596.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654965" 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 (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs28937903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937903;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/rs28937903?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=rs28937903" 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=rs28937903" 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=RCV000004447 OR RCV000201040 OR RCV000532707 OR RCV000597675 OR RCV003466808" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004447, RCV000201040, RCV000532707, RCV000597675, RCV003466808" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004447...</a>
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<p>In 6 unrelated Tunisian patients with congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>), previously designated MDC1C, <a href="#16" class="mim-tip-reference" title="Louhichi, N., Triki, C., Quijano-Roy, S., Richard, P., Makri, S., Meziou, M., Estournet, B., Mrad, S., Romero, N. B., Ayadi, H., Guicheney, P., Fakhfakh, F. <strong>New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities: identification of a founder mutation in Tunisian families.</strong> Neurogenetics 5: 27-34, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14652796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14652796</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14652796[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/10.1007/s10048-003-0165-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14652796">Louhichi et al. (2004)</a> identified a homozygous 1364C-A transversion in the FKRP gene, resulting in an ala455-to-asp (A455D) substitution. All patients came from unrelated consanguineous families. Microsatellite marker analysis suggested a founder effect. In addition to a typical MDC1C phenotype, the patients also had severe psychomotor retardation, mental retardation, and white matter changes and/or cerebellar structural abnormalities on MRI. <a href="#16" class="mim-tip-reference" title="Louhichi, N., Triki, C., Quijano-Roy, S., Richard, P., Makri, S., Meziou, M., Estournet, B., Mrad, S., Romero, N. B., Ayadi, H., Guicheney, P., Fakhfakh, F. <strong>New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities: identification of a founder mutation in Tunisian families.</strong> Neurogenetics 5: 27-34, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14652796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14652796</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14652796[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/10.1007/s10048-003-0165-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14652796">Louhichi et al. (2004)</a> noted the similarities to the patients reported by <a href="#24" class="mim-tip-reference" title="Topaloglu, H., Brockington, M., Yuva, Y., Talim, B., Haliloglu, G., Blake, D., Torelli, S., Brown, S. C., Muntoni, F. <strong>FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts.</strong> Neurology 60: 988-992, 2003. Note: Erratum: Neurology 60: 1875, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654965</a>] [<a href="https://doi.org/10.1212/01.wnl.0000052996.14099.dc" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654965">Topaloglu et al. (2003)</a> (see <a href="#0007">606596.0007</a>-<a href="#0008">606596.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14652796+12654965" 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 (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs28937904 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937904;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/rs28937904?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=rs28937904" 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=rs28937904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Algerian patient with congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>) born of consanguineous parents, <a href="#16" class="mim-tip-reference" title="Louhichi, N., Triki, C., Quijano-Roy, S., Richard, P., Makri, S., Meziou, M., Estournet, B., Mrad, S., Romero, N. B., Ayadi, H., Guicheney, P., Fakhfakh, F. <strong>New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities: identification of a founder mutation in Tunisian families.</strong> Neurogenetics 5: 27-34, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14652796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14652796</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14652796[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/10.1007/s10048-003-0165-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14652796">Louhichi et al. (2004)</a> identified a homozygous 1213G-T transversion in the FKRP gene, resulting in a val405-to-leu (V405L) substitution. The patient also had mental retardation, white matter changes on MRI, and cerebellar cysts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14652796" 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, 5</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> rs28937905 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937905;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/rs28937905?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=rs28937905" 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=rs28937905" 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=RCV000004449 OR RCV003591622 OR RCV004700187" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004449, RCV003591622, RCV004700187" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004449...</a>
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<p>In 8 affected members of a large consanguineous Bedouin family with limb-girdle muscular dystrophy (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#14" class="mim-tip-reference" title="Harel, T., Goldberg, Y., Shalev, S. A., Chervinski, I., Ofir, R., Birk, O. S. <strong>Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation.</strong> Europ. J. Hum. Genet. 12: 38-43, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14523375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14523375</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201087" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14523375">Harel et al. (2004)</a> identified a homozygous 160C-T transition in exon 4 of the FKRP gene, resulting in an arg54-to-trp (R54W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14523375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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> rs104894683 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894683;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/rs104894683?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=rs104894683" 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=rs104894683" 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=RCV000004450 OR RCV000236146 OR RCV000513718 OR RCV001083979 OR RCV002444421" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004450, RCV000236146, RCV000513718, RCV001083979, RCV002444421" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004450...</a>
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<p>In 3 Brazilian sisters with a severe form of LGMD (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">de Paula et al. (2003)</a> identified compound heterozygosity for 2 mutations in the FKRP gene: a 235G-A transition, resulting in a val79-to-met (V79M) substitution, and a 764G-A transition, resulting in a trp255-to-ter (W255X; <a href="#0013">606596.0013</a>) substitution. All 3 patients showed hypotonia at birth; 2 were confined to wheelchairs at ages 11 and 12 years and died of cardiorespiratory failure at ages 14 and 15 years, respectively. Neither mutation was identified in 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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">rs104894689 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894689;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=rs104894689" 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=rs104894689" 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=RCV000004451" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004451" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004451</a>
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<p>For discussion of the 764G-A transition in the FKRP gene, resulting in a trp255-to-ter (W255X; <a href="#0013">606596.0013</a>) substitution, that was found in compound heterozygous state in Brazilian patients with a severe form of LGMD (MDDGC5; 607155) by <a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">de Paula et al. (2003)</a>, see <a href="#0012">606596.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" 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>.0014 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
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FKRP, ARG134TRP
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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> rs104894690 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894690;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/rs104894690?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=rs104894690" 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=rs104894690" 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=RCV000004452 OR RCV002512756" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004452, RCV002512756" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004452...</a>
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<p>In 2 Brazilian sibs, from a consanguineous family, with LGMD (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">de Paula et al. (2003)</a> identified a homozygous 400C-T transition in the FKRP gene, resulting in an arg134-to-trp (R134W) substitution. Ages at onset were 26 and 19 years, respectively. Two clinically unaffected sibs also carried the homozygous R134W mutation; although clinical examination was normal at ages 22 and 31 years, respectively, both had increased serum creatine kinase. The mutation was not identified in 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
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FKRP, VAL300ALA
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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> rs104894691 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894691;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/rs104894691?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=rs104894691" 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=rs104894691" 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=RCV000004453 OR RCV000732974 OR RCV000814162 OR RCV001813735 OR RCV002371759 OR RCV003155013 OR RCV003466810 OR RCV005003334" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004453, RCV000732974, RCV000814162, RCV001813735, RCV002371759, RCV003155013, RCV003466810, RCV005003334" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004453...</a>
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<p>In a Brazilian woman, from a consanguineous family, with LGMD (MDDGC5; <a href="/entry/607155">607155</a>), <a href="#8" class="mim-tip-reference" title="De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M. <strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong> Europ. J. Hum. Genet. 11: 923-930, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14647208">de Paula et al. (2003)</a> identified a homozygous 899T-C transition in the FKRP gene, resulting in a val300-to-ala (V300A) substitution. She had onset at age 14 years and died from pneumonia at age 33 years. Two clinically unaffected sibs also carried the homozygous V300A mutation; although clinical examination was normal at ages 31 and 29 years, respectively, both had increased serum creatine kinase. The mutation was not identified in 200 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</strong>
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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5, INCLUDED
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FKRP, TYR307ASN
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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> rs104894692 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894692;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/rs104894692?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=rs104894692" 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=rs104894692" 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=RCV000004454 OR RCV000004455 OR RCV000494504 OR RCV000805125 OR RCV000844942 OR RCV003488324" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004454, RCV000004455, RCV000494504, RCV000805125, RCV000844942, RCV003488324" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004454...</a>
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<p>In a patient with muscle-eye-brain disease (MDDGA5; <a href="/entry/613153">613153</a>), <a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., Voit, T., Longman, C., Steinbrecher, A., Straub, V., Yuva, Y., Herrmann, R., Sperner, J., Korenke, C., Diesen, C., Dobyns, W. B., Brunner, H. G., van Bokhoven, H., Brockington, M., Muntoni, F. <strong>Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome.</strong> J. Med. Genet. 41: e61, 2004. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121789</a>] [<a href="https://doi.org/10.1136/jmg.2003.013870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15121789">Beltran-Valero de Bernabe et al. (2004)</a> identified a homozygous 919T-A transversion in the FKRP gene, resulting in a tyr307-to-asn (Y307N) substitution in the catalytic domain of the protein. The mutation was not identified in 200 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Mercuri, E., Brockington, M., Straub, V., Quijano-Roy, S., Yuva, Y., Herrmann, R., Brown, S. C., Torelli, S., Dubowitz, V., Blake, D. J., Romero, N. B., Estournet, B., Sewry, C. A., Guicheney, P., Voit, T., Muntoni, F. <strong>Phenotypic spectrum associated with mutations in the fukutin-related protein gene.</strong> Ann. Neurol. 53: 537-542, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666124</a>] [<a href="https://doi.org/10.1002/ana.10559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12666124">Mercuri et al. (2003)</a> reported a patient with LGMD (MDDGC5; <a href="/entry/607155">607155</a>) who was compound heterozygous for 2 mutations in the FKRP gene: L276I (<a href="#0004">606596.0004</a>) and Y307N. The patient had an unusually severe form of the disorder and died in his early teens. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12666124" 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="0017" class="mim-anchor"></a>
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<strong>.0017 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</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">rs104894684 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894684;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=rs104894684" 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=rs104894684" 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=RCV000004456" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004456" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004456</a>
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<p>In a patient with Walker-Warburg syndrome (MDDGA5; <a href="/entry/613153">613153</a>), <a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., Voit, T., Longman, C., Steinbrecher, A., Straub, V., Yuva, Y., Herrmann, R., Sperner, J., Korenke, C., Diesen, C., Dobyns, W. B., Brunner, H. G., van Bokhoven, H., Brockington, M., Muntoni, F. <strong>Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome.</strong> J. Med. Genet. 41: e61, 2004. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121789</a>] [<a href="https://doi.org/10.1136/jmg.2003.013870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15121789">Beltran-Valero de Bernabe et al. (2004)</a> identified a homozygous 953G-A transition in the FKRP gene, resulting in a cys318-to-tyr (C318Y) substitution in the catalytic domain of the protein. The mutation was not identified in 200 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121789" 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>.0018 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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> rs121908110 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908110;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/rs121908110?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=rs121908110" 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=rs121908110" 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=RCV000178346 OR RCV000194089 OR RCV000540601 OR RCV001254718 OR RCV001273521 OR RCV002226441 OR RCV002490307 OR RCV003114175 OR RCV003460429 OR RCV004018553" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000178346, RCV000194089, RCV000540601, RCV001254718, RCV001273521, RCV002226441, RCV002490307, RCV003114175, RCV003460429, RCV004018553" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000178346...</a>
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<p>In 2 unrelated girls of Mexican descent with congenital muscular dystrophy (MDDGB5; <a href="/entry/606612">606612</a>), <a href="#17" class="mim-tip-reference" title="MacLeod, H., Pytel, P., Wollmann, R., Chelmicka-Schorr, E., Silver, K., Anderson, R. B., Waggoner, D., McNally, E. M. <strong>A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex.</strong> Neuromusc. Disord. 17: 285-289, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17336067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17336067</a>] [<a href="https://doi.org/10.1016/j.nmd.2007.01.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17336067">MacLeod et al. (2007)</a> identified a homozygous 1387A-G transition in the FKRP gene, resulting in an asn463-to-asp (N463D) substitution near the C terminus. Both girls had onset of muscle weakness from birth without neurologic or cardiac abnormalities. Skeletal muscle biopsies showed chronic myopathic changes with decreased immunoreactivity for alpha- and beta-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) as well as several sarcoglycans (see, e.g., SGCA; <a href="/entry/600119">600119</a>), suggesting that multiple members of the membrane glycoprotein complex were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17336067" 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>.0019 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</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">rs587777223 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777223;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=rs587777223" 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=rs587777223" 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=RCV000106303 OR RCV000323348" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000106303, RCV000323348" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000106303...</a>
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<p>In 2 sibs, the offspring of consanguineous parents, with a clinical diagnosis of Walker-Warburg syndrome (MDDGA5; <a href="/entry/613153">613153</a>), <a href="#25" class="mim-tip-reference" title="van Reeuwijk, J., Olderode-Berends, M. J. W., van den Elzen, C., Brouwer, O. F., Roscioli, T., van Pampus, M. G., Scheffer, H., Brunner, H. G., van Bokhoven, H., Hol, F. A. <strong>A homozygous FKRP start codon mutation is associated with Walker-Warburg syndrome, the severe end of the clinical spectrum.</strong> Clin. Genet. 78: 275-281, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20236121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20236121</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01384.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20236121">van Reeuwijk et al. (2010)</a> identified a homozygous c.1A-G transition in the FKRP gene, resulting in a met1-to-val (M1V) substitution in the start codon, predicted to result in a complete loss of protein function. The mutation was found by homozygosity mapping combined with candidate gene sequencing. The unaffected parents were heterozygous for the mutation. The first child was born with severe hydrocephalus and showed limited spontaneous movements. He had microphthalmia, asymmetric pupils, absent pupillary light reflexes, and cataracts. Brain MRI showed aqueductal stenosis and small cerebellum and pons with kinking of the brainstem. Muscle biopsy showed muscular dystrophy. The infant died of respiratory distress at 6 days of age. Severe hydrocephalus was diagnosed at about 17 weeks' gestation in a subsequent pregnancy, and the pregnancy was terminated. Autopsy was not performed. <a href="#25" class="mim-tip-reference" title="van Reeuwijk, J., Olderode-Berends, M. J. W., van den Elzen, C., Brouwer, O. F., Roscioli, T., van Pampus, M. G., Scheffer, H., Brunner, H. G., van Bokhoven, H., Hol, F. A. <strong>A homozygous FKRP start codon mutation is associated with Walker-Warburg syndrome, the severe end of the clinical spectrum.</strong> Clin. Genet. 78: 275-281, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20236121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20236121</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01384.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20236121">Van Reeuwijk et al. (2010)</a> predicted that the M1V mutation would result in a null allele, which correlated with the severe phenotype seen in these sibs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20236121" 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>REFERENCES</strong>
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<a id="Ackroyd2009" class="mim-anchor"></a>
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Ackroyd, M. R., Skordis, L., Kaluarachchi, M., Godwin, J., Prior, S., Fidanboylu, M., Piercy, R. J., Muntoni, F., Brown, S. C.
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<strong>Reduced expression of fukutin related protein in mice results in a model for fukutin related protein associated muscular dystrophies.</strong>
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Brain 132: 439-451, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19155270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19155270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19155270" 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/awn335" target="_blank">Full Text</a>]
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Beltran-Valero de Bernabe, D., Voit, T., Longman, C., Steinbrecher, A., Straub, V., Yuva, Y., Herrmann, R., Sperner, J., Korenke, C., Diesen, C., Dobyns, W. B., Brunner, H. G., van Bokhoven, H., Brockington, M., Muntoni, F.
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<strong>Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome.</strong>
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J. Med. Genet. 41: e61, 2004. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2003.013870" target="_blank">Full Text</a>]
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Blaeser, A., Keramaris, E., Chan, Y. M., Sparks, S., Cowley, D., Xiao, X., Lu, Q. L.
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<strong>Mouse models of fukutin-related protein mutations show a wide range of disease phenotypes.</strong>
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Hum. Genet. 132: 923-934, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23591631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23591631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23591631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-013-1302-7" target="_blank">Full Text</a>]
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Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F.
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<strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong>
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Am. J. Hum. Genet. 69: 1198-1209, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592034[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=11592034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/324412" target="_blank">Full Text</a>]
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Brockington, M., Yuva, Y., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Herrmann, R., Anderson, L. V. B., Bashir, R., Burgunder, J.-M., Fallet, S., Romero, N., and 10 others.
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<strong>Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.</strong>
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Hum. Molec. Genet. 10: 2851-2859, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/10.25.2851" target="_blank">Full Text</a>]
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Chan, Y. M., Keramaris-Vrantsis, E., Lidov, H. G., Norton, J. H., Zinchenko, N., Gruber, H. E., Thresher, R., Blake, D. J., Ashar, J., Rosenfeld, J., Lu, Q. L.
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<strong>Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies.</strong>
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Hum. Molec. Genet. 19: 3995-4006, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20675713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20675713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20675713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq314" target="_blank">Full Text</a>]
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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<strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong>
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Am. J. Hum. Genet. 91: 608-620, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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=22981120" 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.2012.08.007" target="_blank">Full Text</a>]
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<a id="De Paula2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M.
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<strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong>
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Europ. J. Hum. Genet. 11: 923-930, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14647208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14647208</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14647208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201066" target="_blank">Full Text</a>]
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<a id="Driss2003" class="mim-anchor"></a>
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<p class="mim-text-font">
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Driss, A., Noguchi, S., Amouri, R., Kefi, M., Sasaki, T., Sugie, K., Souilem, S., Hayashi, Y. K., Shimizu, N., Minoshima, S., Kudoh, J., Hentati, F., Nishino, I.
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<strong>Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.</strong>
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Neurology 60: 1341-1344, 2003.
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[<a href="https://doi.org/10.1212/01.wnl.0000065886.82930.c5" target="_blank">Full Text</a>]
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<a id="Esapa2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Esapa, C. T., Benson, M. A., Schroder, J. E., Martin-Rendon, E., Brockington, M., Brown, S. C., Muntoni, F., Kroger, S., Blake, D. J.
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<strong>Functional requirements for fukutin-related protein in the Golgi apparatus.</strong>
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Hum. Molec. Genet. 11: 3319-3331, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471058</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12471058" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/11.26.3319" target="_blank">Full Text</a>]
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<a id="Esapa2005" class="mim-anchor"></a>
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Esapa, C. T., McIlhinney, R. A. J., Blake, D. J.
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<strong>Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells.</strong>
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Hum. Molec. Genet. 14: 295-305, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15574464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15574464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15574464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi026" target="_blank">Full Text</a>]
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<a id="Frosk2005" class="mim-anchor"></a>
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<div class="">
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Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R.
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<strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong>
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Europ. J. Hum. Genet. 13: 978-982, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15886712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15886712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15886712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201436" target="_blank">Full Text</a>]
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<a id="Frosk2005" class="mim-anchor"></a>
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<div class="">
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Frosk, P., Greenberg, C. R., Tennese, A. A. P., Lamont, R., Nylen, E., Hirst, C., Frappier, D., Roslin, N. M., Zaik, M., Bushby, K., Straub, V., Zatz, M., de Paula, F., Morgan, K., Fujiwara, T. M., Wrogemann, K.
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<strong>The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.</strong>
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Hum. Mutat. 25: 38-44, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15580560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15580560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15580560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20110" target="_blank">Full Text</a>]
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<a id="Harel2004" class="mim-anchor"></a>
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Harel, T., Goldberg, Y., Shalev, S. A., Chervinski, I., Ofir, R., Birk, O. S.
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<strong>Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation.</strong>
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Europ. J. Hum. Genet. 12: 38-43, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14523375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14523375</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14523375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201087" target="_blank">Full Text</a>]
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<a id="Kawahara2010" class="mim-anchor"></a>
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Kawahara, G., Guyon, J. R., Nakamura, Y., Kunkel, L. M.
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<strong>Zebrafish models for human FKRP muscular dystrophies.</strong>
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Hum. Molec. Genet. 19: 623-633, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955119[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=19955119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp528" target="_blank">Full Text</a>]
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<a id="Louhichi2004" class="mim-anchor"></a>
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<div class="">
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Louhichi, N., Triki, C., Quijano-Roy, S., Richard, P., Makri, S., Meziou, M., Estournet, B., Mrad, S., Romero, N. B., Ayadi, H., Guicheney, P., Fakhfakh, F.
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<strong>New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities: identification of a founder mutation in Tunisian families.</strong>
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Neurogenetics 5: 27-34, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14652796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14652796</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14652796[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=14652796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10048-003-0165-9" target="_blank">Full Text</a>]
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<a id="MacLeod2007" class="mim-anchor"></a>
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<div class="">
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MacLeod, H., Pytel, P., Wollmann, R., Chelmicka-Schorr, E., Silver, K., Anderson, R. B., Waggoner, D., McNally, E. M.
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<strong>A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex.</strong>
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Neuromusc. Disord. 17: 285-289, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17336067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17336067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17336067" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2007.01.005" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
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<a id="Mercuri2003" class="mim-anchor"></a>
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<div class="">
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Mercuri, E., Brockington, M., Straub, V., Quijano-Roy, S., Yuva, Y., Herrmann, R., Brown, S. C., Torelli, S., Dubowitz, V., Blake, D. J., Romero, N. B., Estournet, B., Sewry, C. A., Guicheney, P., Voit, T., Muntoni, F.
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<strong>Phenotypic spectrum associated with mutations in the fukutin-related protein gene.</strong>
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Ann. Neurol. 53: 537-542, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666124</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12666124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10559" target="_blank">Full Text</a>]
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<a id="Mercuri2009" class="mim-anchor"></a>
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<div class="">
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Mercuri, E., Messina, S., Bruno, C., Mora, M., Pegoraro, E., Comi, G. P., D'Amico, A., Aiello, C., Biancheri, R., Berardinelli, A., Boffi, P., Cassandrini, D.
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<strong>Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.</strong>
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Neurology 72: 1802-1809, 2009. Note: Erratum: Neurology 93: 371 only, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19299310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19299310</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19299310" 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/10.1212/01.wnl.0000346518.68110.60" target="_blank">Full Text</a>]
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<a id="Mercuri2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mercuri, E., Sewry, C. A., Brown, S. C., Brockington, M., Jungbluth, H., DeVile, C., Counsell, S., Manzur, A., Muntoni, F.
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<strong>Congenital muscular dystrophy with secondary merosin deficiency and normal brain MRI: a novel entity?</strong>
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Neuropediatrics 31: 186-189, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11071142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11071142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11071142" 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/10.1055/s-2000-7460" target="_blank">Full Text</a>]
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<a id="Mercuri2006" class="mim-anchor"></a>
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<div class="">
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Mercuri, E., Topaloglu, H., Brockington, M., Berardinelli, A., Pichiecchio, A., Santorelli, F., Rutherford, M., Talim, B., Ricci, E., Voit, T., Muntoni, F.
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<strong>Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.</strong>
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Arch. Neurol. 63: 251-257, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16476814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16476814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16476814" 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/10.1001/archneur.63.2.251" target="_blank">Full Text</a>]
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<a id="Sveen2006" class="mim-anchor"></a>
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<strong>High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16634037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16634037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16634037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20824" target="_blank">Full Text</a>]
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<a id="Talim2000" class="mim-anchor"></a>
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<div class="">
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Talim, B., Ferreiro, A., Cormand, B., Vignier, N., Oto, A., Gogus, S., Cila, A., Lehesjoki, A.-E., Pihko, H., Guicheney, P., Topaloglu, H.
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<strong>Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci.</strong>
|
|
Neuromusc. Disord. 10: 548-552, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11053680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11053680</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11053680" 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/s0960-8966(00)00140-1" 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="24" class="mim-anchor"></a>
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<a id="Topaloglu2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Topaloglu, H., Brockington, M., Yuva, Y., Talim, B., Haliloglu, G., Blake, D., Torelli, S., Brown, S. C., Muntoni, F.
|
|
<strong>FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts.</strong>
|
|
Neurology 60: 988-992, 2003. Note: Erratum: Neurology 60: 1875, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654965" 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/10.1212/01.wnl.0000052996.14099.dc" 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="25" class="mim-anchor"></a>
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<a id="van Reeuwijk2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Reeuwijk, J., Olderode-Berends, M. J. W., van den Elzen, C., Brouwer, O. F., Roscioli, T., van Pampus, M. G., Scheffer, H., Brunner, H. G., van Bokhoven, H., Hol, F. A.
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<strong>A homozygous FKRP start codon mutation is associated with Walker-Warburg syndrome, the severe end of the clinical spectrum.</strong>
|
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Clin. Genet. 78: 275-281, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20236121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20236121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20236121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2010.01384.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 4/21/2014
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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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Cassandra L. Kniffin - updated : 3/18/2014<br>Ada Hamosh - updated : 2/7/2013<br>George E. Tiller - updated : 2/8/2011<br>Cassandra L. Kniffin - updated : 11/8/2010<br>Cassandra L. Kniffin - updated : 5/29/2008<br>Cassandra L. Kniffin - updated : 2/12/2008<br>George E. Tiller - updated : 11/8/2007<br>Cassandra L. Kniffin - updated : 3/3/2006<br>Cassandra L. Kniffin - updated : 2/10/2006<br>Cassandra L. Kniffin - updated : 1/12/2006<br>Victor A. McKusick - updated : 2/4/2005<br>George E. Tiller - updated : 9/13/2004<br>Cassandra L. Kniffin - updated : 5/7/2004<br>Cassandra L. Kniffin - updated : 3/17/2004<br>Cassandra L. Kniffin - updated : 10/1/2003<br>Cassandra L. Kniffin - updated : 6/10/2003<br>George E. Tiller - updated : 8/22/2002
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</span>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 1/7/2002
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</span>
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</div>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/19/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/08/2019<br>carol : 09/27/2018<br>carol : 09/26/2018<br>carol : 06/08/2018<br>alopez : 12/09/2014<br>alopez : 12/9/2014<br>carol : 10/20/2014<br>mcolton : 10/16/2014<br>carol : 4/23/2014<br>mcolton : 4/22/2014<br>ckniffin : 4/21/2014<br>carol : 3/19/2014<br>ckniffin : 3/18/2014<br>alopez : 2/13/2013<br>alopez : 2/13/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>wwang : 6/13/2011<br>terry : 3/14/2011<br>wwang : 3/11/2011<br>terry : 2/8/2011<br>carol : 11/11/2010<br>carol : 11/10/2010<br>ckniffin : 11/8/2010<br>ckniffin : 12/4/2009<br>wwang : 6/23/2009<br>wwang : 7/2/2008<br>ckniffin : 5/29/2008<br>wwang : 2/20/2008<br>ckniffin : 2/12/2008<br>wwang : 12/3/2007<br>wwang : 11/26/2007<br>terry : 11/8/2007<br>wwang : 8/3/2007<br>ckniffin : 7/24/2007<br>ckniffin : 7/24/2007<br>wwang : 3/10/2006<br>ckniffin : 3/3/2006<br>wwang : 2/20/2006<br>ckniffin : 2/10/2006<br>wwang : 1/18/2006<br>ckniffin : 1/12/2006<br>carol : 2/16/2005<br>ckniffin : 2/15/2005<br>terry : 2/4/2005<br>tkritzer : 9/20/2004<br>tkritzer : 9/13/2004<br>carol : 7/27/2004<br>tkritzer : 5/10/2004<br>ckniffin : 5/7/2004<br>tkritzer : 3/18/2004<br>ckniffin : 3/17/2004<br>terry : 11/10/2003<br>cwells : 11/7/2003<br>carol : 10/3/2003<br>ckniffin : 10/1/2003<br>carol : 6/11/2003<br>ckniffin : 6/10/2003<br>carol : 6/10/2003<br>ckniffin : 5/29/2003<br>ckniffin : 12/27/2002<br>cwells : 8/22/2002<br>joanna : 1/18/2002<br>cwells : 1/14/2002<br>cwells : 1/10/2002
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606596
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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FUKUTIN-RELATED PROTEIN; FKRP
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: FKRP</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 718180000;
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<strong>ICD10CM:</strong> G71.038;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 19q13.32
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:46,744,760-46,758,575 </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>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="3">
|
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<span class="mim-font">
|
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19q13.32
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5
|
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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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613153
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal recessive
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Muscular dystrophy-dystroglycanopathy (congenital with or without impaired intellectual development), type B, 5
|
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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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606612
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
607155
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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3
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
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|
|
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>Brockington et al. (2001) identified the fukutin-related protein gene (FKRP) by database screening with the mouse fukutin sequence as query. The human version of the sequence was determined by a combination of EST assembly, RT-PCR, and RACE. The cDNA encodes a deduced 495-amino acid protein. Sequence analysis predicted a molecular organization similar to that found in several Golgi-resident glycosyltransferases. Northern blot analysis detected a 4.0-kb FKRP transcript expressed predominantly in skeletal muscle, placenta, and heart, and relatively weakly in other tissues. </p><p>Using transfection experiments, Esapa et al. (2002) determined that FKRP and fukutin (FKTN; 607440) are targeted to the medial Golgi apparatus through their N termini and transmembrane domains. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Brockington et al. (2001) determined that the 12-kb FKRP gene is composed of 3 noncoding exons and a single large exon of 3.8 kb that contains part of the 5-prime untranslated region (UTR) and the entire open reading frame (ORF) and 3-prime UTR. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>By radiation hybrid analysis, Brockington et al. (2001) localized the FKRP gene to chromosome 19q13.3. </p>
|
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</span>
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>Mutation in the FKRP gene can cause 3 different forms of muscular dystrophy-dystroglycanopathy (MDDG): a severe congenital form with brain and eye anomalies (type A5; MDDGA5; 613153), formerly designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB); a less severe congenital form with or without impaired intellectual development (type B5; MDDGB5; 606612); and a milder limb-girdle form (type C5; MDDGC5; 607155), also known as LGMDR9 and LGMD2I.</p><p>In 7 families with a distinct form of congenital muscular dystrophy (MDDGB5; 606612), Brockington et al. (2001) identified 11 different mutations in the FKRP gene (see, e.g., 606596.0001-606596.0003). Nine were missense mutations and 2 were nonsense mutations. In 4 families, the affected individuals were compound heterozygotes; in the other 3, the patients were homozygotes. </p><p>In 17 of 25 families with limb-girdle muscular dystrophy (MDDGC5; 607155), Brockington et al. (2001) found mutations in the FKRP gene. Affected individuals from 15 of 17 families had an identical L276I mutation (606596.0004); individuals in 5 families were homozygous for this mutation. Linkage analysis identified at least 2 possible haplotypes in linkage disequilibrium with this mutation. Patients with the L276I change had the clinically less severe phenotype, suggesting that this is a less disruptive FKRP mutation than those found in MDDGB5. A variable reduction of alpha-dystroglycan (DAG1; 128239) expression was observed in the skeletal muscle biopsy of all individuals studied. In addition, several cases showed a deficiency of laminin-2 (LAMA2; 156225) either by immunocytochemistry or Western blotting. </p><p>Esapa et al. (2002) found that overexpression of FKRP in CHO cells altered the posttranslational processing of alpha- and beta-dystroglycan, thus inhibiting maturation of the 2 isoforms. Mutations in the DxD motif or in the Golgi-targeting sequence, which cause inefficient trafficking of FKRP to the Golgi apparatus, did not alter dystroglycan processing in vitro. The P448L mutation in FKRP (606596.0003) resulted in mislocalization of the mutant protein and disruption in dystroglycan processing. Esapa et al. (2002) concluded that FKRP is required for the posttranslational modification of dystroglycan. They suggested that aberrant processing of dystroglycan caused by a mislocalized FKRP mutant could be a novel mechanism that causes congenital muscular dystrophy. </p><p>In 16 patients with LGMD (MDDGC5; 607155) from 13 Brazilian families, de Paula et al. (2003) identified 10 distinct mutations, including 9 novel mutations, in the FKRP gene (see, e.g., 606596.0012-606596.0015). The most common mutation, L276I (606596.0004), was identified in 9 of 26 alleles. </p><p>Beltran-Valero de Bernabe et al. (2004) identified homozygous mutations in the FKRP gene (Y307N, 606596.0016 and C318Y, 606596.0017) in 2 unrelated patients with muscle-eye-brain disease and Walker-Warburg syndrome (MDDGA5; 613153), respectively. Both disorders are characterized by severe disruption of brain and eye structure in addition to muscular dystrophy. The findings expanded the phenotypic spectrum of disorders associated with mutation in the FKRP gene. </p><p>Mercuri et al. (2009) identified FKRP mutations in 7 (9%) of 81 Italian patients with a dystroglycanopathy. Three had MEB and 4 had a less severe congenital muscular dystrophy. Three patients had normal brain MRI. In general, the more severe phenotypes appeared to be associated with mutations predicted to result in severe disruption of the gene. </p>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In transfected COS-7 cells, Esapa et al. (2005) showed that FKRP mutants, which are associated with the more severe disease phenotypes (S221R, 606596.0008; A455D, 606596.0009; P448L, 606596.0003) were retained in the endoplasmic reticulum (ER), whereas the wildtype protein and the mutant L276I (606596.0004) that causes LGMD (MDDGC5) were found predominantly in the Golgi apparatus. The ER-retained proteins had a shorter half-life than the wildtype FKRP and were preferentially degraded by the proteasome. Furthermore, calnexin (CANX; 114217) bound preferentially to the ER-retained mutants, suggesting that it may participate in the quality control pathway for FKRP. </p><p>Sveen et al. (2006) identified FKRP mutations in 38 of 99 Danish individuals with a clinical diagnosis of limb-girdle muscular dystrophy. Of the 38 individuals, 27 were homozygous for L276I, and 11 were compound heterozygous for L276I and another pathogenic FKRP mutation. The homozygous patients had later onset, milder clinical progression, and less muscle weakness compared to compound heterozygous patients, all of whom were wheelchair-bound by their mid-twenties. Cardiac and respiratory involvement was found in both groups. Nine L276I homozygous, but no compound heterozygous, patients had initial symptoms of exertional myoglobinuria. The L276I variant was identified in 1 of 200 control alleles. </p><p>In a retrospective review of brain MRI in patients with FKRP mutations, Mercuri et al. (2006) found a range of various patterns. Five of 13 patients had normal imaging results and normal neurologic function. Three patients had isolated cerebellar cysts and mental retardation without other abnormal brain structure. Of the 5 remaining patients, 2 had features of muscle-eye-brain disease, 1 had features of Walker-Warburg syndrome, and 2 had cerebellar cysts with nodular heterotopia and cerebellar dysplasia, respectively. There was no correlation with severity of the neurologic involvement and FKRP mutation. Mercuri et al. (2006) postulated that the variability may be related to the severity of disruption of alpha-dystroglycan glycosylation. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<p>Ackroyd et al. (2009) found that mice with a homozygous knockin Y307N (606596.0016) mutation in the Fkrp showed no distinguishable phenotype from wildtype mice up to 6 months of age. Fkrp transcript levels were similar to controls. However, mice homozygous for the Y307N mutation and a neomycin cassette in intron 2 of the Fkrp gene died soon after birth. These mice showed a reduction of alpha-dystroglycan in muscle, eye and brain, and had reduced levels of Fkrp transcript (about 40% of control values). The phenotype was consistent with muscle-eye-brain disease in humans; mutant mice showed decreased muscle mass, perturbation of the limiting membrane of the eye, and a disturbance in neuronal migration. The results suggested that the generation of a mouse model for FKRP-related muscular dystrophy requires a knockdown hypomorph Fkrp allele rather than a knockin missense mutation in order to give rise to a disease phenotype. </p><p>Kawahara et al. (2010) reported that downregulating fkrp expression in zebrafish by 2 different morpholinos resulted in embryos that had developmental defects similar to those observed in human muscular dystrophies associated with human FKRP mutations. The fkrp morphants showed phenotypes involving alterations in somitic structure and muscle fiber organization, as well as defects in developing eye morphology. Additionally, they were found to have a reduction in alpha-dystroglycan (DAG1; 128239) glycosylation and a shortened myofiber length. Coinjection of fish or human FKRP mRNA along with the morpholino restored normal development, alpha-dystroglycan glycosylation, and laminin- binding activity of alpha-dystroglycan in the morphants. Coinjection of the human FKRP mRNA containing mutations causative of human disorders could not significantly restore their phenotypes. Morphant zebrafish harboring human FKRP mutations showed a wide phenotypic range, similar to that seen in humans. </p><p>Chan et al. (2010) generated a transgenic mouse model with a P448L Fkrp mutation (606596.0003) and a neomycin cassette. About one-third of homozygous P448L mice died at birth or within 2 days. The remaining mice recapitulated the features of FKRP-associated muscular dystrophy, including muscle weakness, dystrophic pathology in skeletal muscles, increased serum creatine kinase, and eye and brain abnormalities, such as hydrocephalus and abnormal neuronal migration. Biochemical analysis showed that alpha-DAG was not functionally glycosylated. In another mouse model, homozygous deletion of the C-terminal consensus DxD motif (E310del/E310del) resulted in early embryonic lethality. Only a few compound heterozygous mice (P448L/E310del) were born, and they died at birth. The findings confirmed a critical role of FKRP in posttranslational modification of alpha-DAG. In a follow-up to the study of Chan et al. (2010), Blaeser et al. (2013) generated several mouse models carrying different combinations of mutations in the Fkrp gene, including P448L, E310del, and L276I (606596.0004). One surviving mouse that was compound heterozygous for P448L/E310del showed a severe dystrophic phenotype, with muscle degeneration, hydrocephalus, and abnormal migration of neurons in the cerebral cortex and cerebellum. In contrast, most of the L276I/P448L or L276I/E310del compound heterozygous mice were normal, but some showed later onset of mild muscle weakness associated with increased serum creatine kinase and mild muscular dystrophy without brain abnormalities. Skeletal muscle from these mutant mice showed less severe decreases in Fkrp expression and higher amounts of functional glycosylated DAG compared to P448L/E310del, P448L/P448L, and E310del/E310del mice. Removal of the neomycin cassette from the mutant alleles resulted in increased Fkrp levels and attenuated the phenotypes in all mutants. The findings indicated that L276I can provide sufficient activity to avoid neurologic defects, suggesting that different missense mutations affect the function of FKRP, resulting in phenotypic variability. The wide range of disease phenotypes observed in these mice recapitulated the variable phenotypic severity observed in humans with different FKRP mutations. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>19 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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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FKRP, TYR309CYS
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<br />
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SNP: rs104894679,
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gnomAD: rs104894679,
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ClinVar: RCV001851646, RCV002226438, RCV003144103, RCV003466806
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</span>
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</div>
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<span class="mim-text-font">
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<p>Mercuri et al. (2000) described the clinical features of 2 sibs in a Scottish family who appeared to be affected by a novel form of congenital muscular dystrophy (MDDGB5; 606612). Both children presented soon after birth with hypotonia and feeding difficulties. They never acquired the ability to walk because of severe weakness, which also affected their facial muscles. Weakness was greater in the arms than legs, with prominent wasting of the deltoids and pectoral muscles, whereas both calf and quadriceps muscles were hypertrophied. Cognitive development, intelligence, and vision were normal, as was brain MRI. Serum creatine kinase was markedly elevated. The older sib died suddenly at age 7 years, following an upper respiratory tract infection. Brockington et al. (2001) found that these affected sibs were compound heterozygotes for mutations in the FKRP gene: tyr309-to-cys (Y309C) and ser385-to-ter (S385X; 606596.0002). </p>
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</span>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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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FKRP, SER385TER
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<br />
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SNP: rs104894680,
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gnomAD: rs104894680,
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ClinVar: RCV000634067, RCV002226439, RCV003137491, RCV003352746, RCV003460427, RCV005025007
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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 ser385-to-ter (S385X) mutation in the FKRP gene that was found in compound heterozygous state in patients with a form of congenital muscular dystrophy (MDDGB5; 606612) by Brockington et al. (2001), see 606596.0001. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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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FKRP, PRO448LEU
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<br />
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SNP: rs104894681,
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gnomAD: rs104894681,
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ClinVar: RCV000360542, RCV000763056, RCV002226440, RCV002381242, RCV003466807, RCV003591620
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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 consanguineous family from Libya with a severe form of congenital muscular dystrophy (MDDGB5; 606612), Brockington et al. (2001) found that the 1 affected child was homozygous for a pro448-to-leu (P448L) missense mutation in the FKRP gene. The patient presented in the first few weeks of life with hypotonia and feeding difficulties, followed by motor delay. On examination at age 16 months, she could not walk and was weaker in her arms than in her legs. She had calf hypertrophy and facial weakness. Serum creatine kinase was very high, and she had a myopathic EMG. Her intelligence was normal. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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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FKRP, LEU276ILE ({dbSNP rs28937900})
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<br />
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SNP: rs28937900,
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gnomAD: rs28937900,
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ClinVar: RCV000004442, RCV000082182, RCV000226653, RCV000231711, RCV000503787, RCV000612115, RCV000626960, RCV000660622, RCV001197775, RCV001329320, RCV001526640, RCV002222338, RCV002408451, RCV003993736, RCV004532287, RCV004776425, RCV004776426
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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 15 of 17 families with autosomal recessive limb-girdle muscular dystrophy (MDDGC5; 607155), Brockington et al. (2001) found homozygosity or compound heterozygosity for an 826C-A transversion in the FKRP gene, predicted to result in a substitution of isoleucine for leucine 276 (L276I). Patients with the L276I change had the clinically less severe phenotype, suggesting that this is a less disruptive FKRP mutation than those found in patients with MDDGB5; see, e.g., 606596.0001. </p><p>Mercuri et al. (2003) reported a patient with limb-girdle muscular dystrophy who was compound heterozygous for 2 mutations in the FKRP gene: L276I and Y307N (606596.0016). The patient had an unusually severe form of the disorder and died in his early teens. </p><p>De Paula et al. (2003) identified the L276I mutation in 9 of 26 mutated alleles among 13 Brazilian families with LGMD (MDDGC5). </p><p>In affected members of 5 Hutterite families with autosomal recessive LGMD, Frosk et al. (2005) identified homozygosity for the L276I mutation. A single common haplotype surrounding the FKRP gene was identified in the Hutterite LGMD patients, and an identical core haplotype was also found in 19 other non-Hutterite LGMD patients from Europe, Canada, and Brazil, carrying the L276I mutation. This finding indicated that the L276I dispersed from populations of European origin. </p><p>Frosk et al. (2005) reported a Hutterite family in which 2 boys, aged 7 and 10 years, were homozygous for both the L276I mutation and an LGMD2H (LGMDR8; 254110)-related TRIM32 mutation (D487N; 602290.0001). Although they presented at an early age with exercise intolerance and increased serum creatine kinase, the clinical phenotype was not significantly more severe than that of patients with isolated disease. Both parents and 3 other sibs were carriers of the L276I mutation and homozygous for the D487N mutation, with highly variable phenotypic expression. </p><p>Sveen et al. (2006) identified the L276I mutation in 38 Danish patients with LGMD, of whom 27 were homozygous, and 11 were compound heterozygous with another pathogenic FKRP mutation. The variant was detected in 1 of 200 control alleles. </p><p>Among 1,127 Schmiedeleut (S-leut) Hutterites from the United States, Chong et al. (2012) found 121 heterozygotes and 3 homozygotes for the L276I mutation in the FKRP gene, for a frequency of 0.107, or 1 in 9.5. The carrier frequency in other populations is 1 in 300 (Frosk et al., 2005). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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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FKRP, 4-BP INS, NT390
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<br />
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SNP: rs587777823,
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ClinVar: RCV000004443
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an individual with early-onset limb-girdle muscular dystrophy (MDDGC5; 607155), Brockington et al. (2001), described compound heterozygosity for mutations in the FKRP gene. One allele contained the recurrent L276I mutation (606596.0004), whereas the other allele harbored a 4-bp insertion TACC (390insTACC), which is predicted to generate a premature stop codon at the position of gly132. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</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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FKRP, TER496ARG
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<br />
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SNP: rs104894682,
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gnomAD: rs104894682,
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ClinVar: RCV000004444, RCV000471321, RCV000501528, RCV000725596, RCV002222339
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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 consanguineous Tunisian family in which 13 members had limb-girdle muscular dystrophy (MDDGC5; 607155), Driss et al. (2003) identified a homozygous 1486T-A change in the FKRP gene, which abolishes a stop codon and is predicted to add 21 amino acids to the C-terminal end of the protein. The patients had symmetric proximal muscle weakness and wasting in all 4 limbs. No heart involvement was found. Immunohistochemical and immunoblot analysis showed abnormal expression of alpha-dystroglycan and alpha-2 laminin, supporting the hypothesis that FKRP has a role in the interaction between components of the extracellular matrix. </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 (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</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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FKRP, PRO316THR
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<br />
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SNP: rs28937901,
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gnomAD: rs28937901,
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ClinVar: RCV000004445, RCV000675047, RCV003144104, RCV003591621
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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 patient with severe merosin-deficient congenital muscular dystrophy (MDDGB5; 606612) reported by Talim et al. (2000), Topaloglu et al. (2003) identified a homozygous 946C-A transversion in the FKRP gene, resulting in a pro316-to-thr (P316T) substitution. The patient was from a consanguineous family, and showed hypotonia, muscle weakness, a myopathic face, and high-arched palate by age 1.5 years. She also had lordosis and scoliosis, and was never able to stand or walk. In addition, she had mild mental retardation and multiple small cysts in the cerebellar cortical and subcortical areas of the brain. Also see 606596.0008. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</strong>
|
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</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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FKRP, SER221ARG
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<br />
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SNP: rs28937902,
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|
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ClinVar: RCV000004446, RCV003460428
|
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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 patient with congenital muscular dystrophy (MDDGB5; 606612), Topaloglu et al. (2003) identified a homozygous 663C-A transversion in the FKRP gene, resulting in a ser221-to-arg (S221R) substitution. In addition to the characteristic features of weakness, hypotonia, dystrophic muscle biopsy, and inability to walk, the patient also had mild mental retardation and cerebellar cysts. The authors noted that mental retardation and structural brain changes are not usually part of the clinical spectrum of patients with FKRP mutations, and that these findings may expand the phenotypic spectrum. Also see 606596.0007. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0009 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</strong>
|
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</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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FKRP, ALA455ASP
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<br />
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SNP: rs28937903,
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gnomAD: rs28937903,
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ClinVar: RCV000004447, RCV000201040, RCV000532707, RCV000597675, RCV003466808
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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 6 unrelated Tunisian patients with congenital muscular dystrophy (MDDGB5; 606612), previously designated MDC1C, Louhichi et al. (2004) identified a homozygous 1364C-A transversion in the FKRP gene, resulting in an ala455-to-asp (A455D) substitution. All patients came from unrelated consanguineous families. Microsatellite marker analysis suggested a founder effect. In addition to a typical MDC1C phenotype, the patients also had severe psychomotor retardation, mental retardation, and white matter changes and/or cerebellar structural abnormalities on MRI. Louhichi et al. (2004) noted the similarities to the patients reported by Topaloglu et al. (2003) (see 606596.0007-606596.0008). </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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|
<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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FKRP, VAL405LEU
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<br />
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SNP: rs28937904,
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gnomAD: rs28937904,
|
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|
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|
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ClinVar: RCV000004448, RCV003466809
|
|
|
|
|
|
</span>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Algerian patient with congenital muscular dystrophy (MDDGB5; 606612) born of consanguineous parents, Louhichi et al. (2004) identified a homozygous 1213G-T transversion in the FKRP gene, resulting in a val405-to-leu (V405L) substitution. The patient also had mental retardation, white matter changes on MRI, and cerebellar cysts. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
|
|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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FKRP, ARG54TRP
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<br />
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SNP: rs28937905,
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gnomAD: rs28937905,
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|
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ClinVar: RCV000004449, RCV003591622, RCV004700187
|
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 affected members of a large consanguineous Bedouin family with limb-girdle muscular dystrophy (MDDGC5; 607155), Harel et al. (2004) identified a homozygous 160C-T transition in exon 4 of the FKRP gene, resulting in an arg54-to-trp (R54W) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
FKRP, VAL79MET
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<br />
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SNP: rs104894683,
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|
|
gnomAD: rs104894683,
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|
|
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|
|
ClinVar: RCV000004450, RCV000236146, RCV000513718, RCV001083979, RCV002444421
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Brazilian sisters with a severe form of LGMD (MDDGC5; 607155), de Paula et al. (2003) identified compound heterozygosity for 2 mutations in the FKRP gene: a 235G-A transition, resulting in a val79-to-met (V79M) substitution, and a 764G-A transition, resulting in a trp255-to-ter (W255X; 606596.0013) substitution. All 3 patients showed hypotonia at birth; 2 were confined to wheelchairs at ages 11 and 12 years and died of cardiorespiratory failure at ages 14 and 15 years, respectively. Neither mutation was identified in 200 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, TRP255TER
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs104894689,
|
|
|
|
|
|
|
|
ClinVar: RCV000004451
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 764G-A transition in the FKRP gene, resulting in a trp255-to-ter (W255X; 606596.0013) substitution, that was found in compound heterozygous state in Brazilian patients with a severe form of LGMD (MDDGC5; 607155) by de Paula et al. (2003), see 606596.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, ARG134TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894690,
|
|
|
|
|
|
gnomAD: rs104894690,
|
|
|
|
|
|
ClinVar: RCV000004452, RCV002512756
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Brazilian sibs, from a consanguineous family, with LGMD (MDDGC5; 607155), de Paula et al. (2003) identified a homozygous 400C-T transition in the FKRP gene, resulting in an arg134-to-trp (R134W) substitution. Ages at onset were 26 and 19 years, respectively. Two clinically unaffected sibs also carried the homozygous R134W mutation; although clinical examination was normal at ages 22 and 31 years, respectively, both had increased serum creatine kinase. The mutation was not identified in 200 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, VAL300ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894691,
|
|
|
|
|
|
gnomAD: rs104894691,
|
|
|
|
|
|
ClinVar: RCV000004453, RCV000732974, RCV000814162, RCV001813735, RCV002371759, RCV003155013, RCV003466810, RCV005003334
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Brazilian woman, from a consanguineous family, with LGMD (MDDGC5; 607155), de Paula et al. (2003) identified a homozygous 899T-C transition in the FKRP gene, resulting in a val300-to-ala (V300A) substitution. She had onset at age 14 years and died from pneumonia at age 33 years. Two clinically unaffected sibs also carried the homozygous V300A mutation; although clinical examination was normal at ages 31 and 29 years, respectively, both had increased serum creatine kinase. The mutation was not identified in 200 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, TYR307ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894692,
|
|
|
|
|
|
gnomAD: rs104894692,
|
|
|
|
|
|
ClinVar: RCV000004454, RCV000004455, RCV000494504, RCV000805125, RCV000844942, RCV003488324
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with muscle-eye-brain disease (MDDGA5; 613153), Beltran-Valero de Bernabe et al. (2004) identified a homozygous 919T-A transversion in the FKRP gene, resulting in a tyr307-to-asn (Y307N) substitution in the catalytic domain of the protein. The mutation was not identified in 200 controls. </p><p>Mercuri et al. (2003) reported a patient with LGMD (MDDGC5; 607155) who was compound heterozygous for 2 mutations in the FKRP gene: L276I (606596.0004) and Y307N. The patient had an unusually severe form of the disorder and died in his early teens. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, CYS318TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894684,
|
|
|
|
|
|
|
|
ClinVar: RCV000004456
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Walker-Warburg syndrome (MDDGA5; 613153), Beltran-Valero de Bernabe et al. (2004) identified a homozygous 953G-A transition in the FKRP gene, resulting in a cys318-to-tyr (C318Y) substitution in the catalytic domain of the protein. The mutation was not identified in 200 controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, ASN463ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908110,
|
|
|
|
|
|
gnomAD: rs121908110,
|
|
|
|
|
|
ClinVar: RCV000178346, RCV000194089, RCV000540601, RCV001254718, RCV001273521, RCV002226441, RCV002490307, RCV003114175, RCV003460429, RCV004018553
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated girls of Mexican descent with congenital muscular dystrophy (MDDGB5; 606612), MacLeod et al. (2007) identified a homozygous 1387A-G transition in the FKRP gene, resulting in an asn463-to-asp (N463D) substitution near the C terminus. Both girls had onset of muscle weakness from birth without neurologic or cardiac abnormalities. Skeletal muscle biopsies showed chronic myopathic changes with decreased immunoreactivity for alpha- and beta-dystroglycan (DAG1; 128239) as well as several sarcoglycans (see, e.g., SGCA; 600119), suggesting that multiple members of the membrane glycoprotein complex were affected. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKRP, MET1VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777223,
|
|
|
|
|
|
|
|
ClinVar: RCV000106303, RCV000323348
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, the offspring of consanguineous parents, with a clinical diagnosis of Walker-Warburg syndrome (MDDGA5; 613153), van Reeuwijk et al. (2010) identified a homozygous c.1A-G transition in the FKRP gene, resulting in a met1-to-val (M1V) substitution in the start codon, predicted to result in a complete loss of protein function. The mutation was found by homozygosity mapping combined with candidate gene sequencing. The unaffected parents were heterozygous for the mutation. The first child was born with severe hydrocephalus and showed limited spontaneous movements. He had microphthalmia, asymmetric pupils, absent pupillary light reflexes, and cataracts. Brain MRI showed aqueductal stenosis and small cerebellum and pons with kinking of the brainstem. Muscle biopsy showed muscular dystrophy. The infant died of respiratory distress at 6 days of age. Severe hydrocephalus was diagnosed at about 17 weeks' gestation in a subsequent pregnancy, and the pregnancy was terminated. Autopsy was not performed. Van Reeuwijk et al. (2010) predicted that the M1V mutation would result in a null allele, which correlated with the severe phenotype seen in these sibs. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
</div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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Ackroyd, M. R., Skordis, L., Kaluarachchi, M., Godwin, J., Prior, S., Fidanboylu, M., Piercy, R. J., Muntoni, F., Brown, S. C.
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<strong>Reduced expression of fukutin related protein in mice results in a model for fukutin related protein associated muscular dystrophies.</strong>
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Beltran-Valero de Bernabe, D., Voit, T., Longman, C., Steinbrecher, A., Straub, V., Yuva, Y., Herrmann, R., Sperner, J., Korenke, C., Diesen, C., Dobyns, W. B., Brunner, H. G., van Bokhoven, H., Brockington, M., Muntoni, F.
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<strong>Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome.</strong>
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J. Med. Genet. 41: e61, 2004. Note: Electronic Article.
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Blaeser, A., Keramaris, E., Chan, Y. M., Sparks, S., Cowley, D., Xiao, X., Lu, Q. L.
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<strong>Mouse models of fukutin-related protein mutations show a wide range of disease phenotypes.</strong>
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Brockington, M., Blake, D. J., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Ponting, C. P., Estournet, B., Romero, N. B., Mercuri, E., Voit, T., Sewry, C. A., Guicheney, P., Muntoni, F.
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<strong>Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan.</strong>
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Brockington, M., Yuva, Y., Prandini, P., Brown, S. C., Torelli, S., Benson, M. A., Herrmann, R., Anderson, L. V. B., Bashir, R., Burgunder, J.-M., Fallet, S., Romero, N., and 10 others.
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<strong>Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.</strong>
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Hum. Molec. Genet. 10: 2851-2859, 2001.
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[PubMed: 11741828]
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Chan, Y. M., Keramaris-Vrantsis, E., Lidov, H. G., Norton, J. H., Zinchenko, N., Gruber, H. E., Thresher, R., Blake, D. J., Ashar, J., Rosenfeld, J., Lu, Q. L.
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<strong>Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies.</strong>
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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De Paula, F., Vieira, N., Starling, A., Yamamoto, L. U., Lima, B., de Cassia Pavanello, R., Vainzof, M., Nigro, V., Zatz, M.
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<strong>Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.</strong>
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Europ. J. Hum. Genet. 11: 923-930, 2003.
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[PubMed: 14647208]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201066]
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<p class="mim-text-font">
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Driss, A., Noguchi, S., Amouri, R., Kefi, M., Sasaki, T., Sugie, K., Souilem, S., Hayashi, Y. K., Shimizu, N., Minoshima, S., Kudoh, J., Hentati, F., Nishino, I.
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<strong>Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.</strong>
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Neurology 60: 1341-1344, 2003.
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[PubMed: 12707439]
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[Full Text: https://doi.org/10.1212/01.wnl.0000065886.82930.c5]
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</p>
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</li>
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<p class="mim-text-font">
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Esapa, C. T., Benson, M. A., Schroder, J. E., Martin-Rendon, E., Brockington, M., Brown, S. C., Muntoni, F., Kroger, S., Blake, D. J.
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<strong>Functional requirements for fukutin-related protein in the Golgi apparatus.</strong>
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Hum. Molec. Genet. 11: 3319-3331, 2002.
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[PubMed: 12471058]
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[Full Text: https://doi.org/10.1093/hmg/11.26.3319]
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</p>
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<p class="mim-text-font">
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Esapa, C. T., McIlhinney, R. A. J., Blake, D. J.
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<strong>Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells.</strong>
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Hum. Molec. Genet. 14: 295-305, 2005.
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[PubMed: 15574464]
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[Full Text: https://doi.org/10.1093/hmg/ddi026]
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</p>
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<p class="mim-text-font">
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Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R.
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<strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong>
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Europ. J. Hum. Genet. 13: 978-982, 2005.
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[PubMed: 15886712]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201436]
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<p class="mim-text-font">
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Frosk, P., Greenberg, C. R., Tennese, A. A. P., Lamont, R., Nylen, E., Hirst, C., Frappier, D., Roslin, N. M., Zaik, M., Bushby, K., Straub, V., Zatz, M., de Paula, F., Morgan, K., Fujiwara, T. M., Wrogemann, K.
|
|
<strong>The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.</strong>
|
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Hum. Mutat. 25: 38-44, 2005.
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[PubMed: 15580560]
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[Full Text: https://doi.org/10.1002/humu.20110]
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Harel, T., Goldberg, Y., Shalev, S. A., Chervinski, I., Ofir, R., Birk, O. S.
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<strong>Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation.</strong>
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Europ. J. Hum. Genet. 12: 38-43, 2004.
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[PubMed: 14523375]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201087]
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Kawahara, G., Guyon, J. R., Nakamura, Y., Kunkel, L. M.
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<strong>Zebrafish models for human FKRP muscular dystrophies.</strong>
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Hum. Molec. Genet. 19: 623-633, 2010.
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[PubMed: 19955119]
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[Full Text: https://doi.org/10.1093/hmg/ddp528]
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Louhichi, N., Triki, C., Quijano-Roy, S., Richard, P., Makri, S., Meziou, M., Estournet, B., Mrad, S., Romero, N. B., Ayadi, H., Guicheney, P., Fakhfakh, F.
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<strong>New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities: identification of a founder mutation in Tunisian families.</strong>
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Neurogenetics 5: 27-34, 2004.
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[PubMed: 14652796]
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[Full Text: https://doi.org/10.1007/s10048-003-0165-9]
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MacLeod, H., Pytel, P., Wollmann, R., Chelmicka-Schorr, E., Silver, K., Anderson, R. B., Waggoner, D., McNally, E. M.
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<strong>A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex.</strong>
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Neuromusc. Disord. 17: 285-289, 2007.
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[PubMed: 17336067]
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[Full Text: https://doi.org/10.1016/j.nmd.2007.01.005]
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Mercuri, E., Brockington, M., Straub, V., Quijano-Roy, S., Yuva, Y., Herrmann, R., Brown, S. C., Torelli, S., Dubowitz, V., Blake, D. J., Romero, N. B., Estournet, B., Sewry, C. A., Guicheney, P., Voit, T., Muntoni, F.
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<strong>Phenotypic spectrum associated with mutations in the fukutin-related protein gene.</strong>
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Ann. Neurol. 53: 537-542, 2003.
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[PubMed: 12666124]
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[Full Text: https://doi.org/10.1002/ana.10559]
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Mercuri, E., Messina, S., Bruno, C., Mora, M., Pegoraro, E., Comi, G. P., D'Amico, A., Aiello, C., Biancheri, R., Berardinelli, A., Boffi, P., Cassandrini, D.
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<strong>Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.</strong>
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Neurology 72: 1802-1809, 2009. Note: Erratum: Neurology 93: 371 only, 2019.
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[PubMed: 19299310]
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[Full Text: https://doi.org/10.1212/01.wnl.0000346518.68110.60]
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Mercuri, E., Sewry, C. A., Brown, S. C., Brockington, M., Jungbluth, H., DeVile, C., Counsell, S., Manzur, A., Muntoni, F.
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<strong>Congenital muscular dystrophy with secondary merosin deficiency and normal brain MRI: a novel entity?</strong>
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Neuropediatrics 31: 186-189, 2000.
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[PubMed: 11071142]
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Mercuri, E., Topaloglu, H., Brockington, M., Berardinelli, A., Pichiecchio, A., Santorelli, F., Rutherford, M., Talim, B., Ricci, E., Voit, T., Muntoni, F.
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<strong>Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.</strong>
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Arch. Neurol. 63: 251-257, 2006.
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Sveen, M.-L., Schwartz, M., Vissing, J.
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<strong>High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark.</strong>
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[PubMed: 16634037]
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[Full Text: https://doi.org/10.1002/ana.20824]
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Talim, B., Ferreiro, A., Cormand, B., Vignier, N., Oto, A., Gogus, S., Cila, A., Lehesjoki, A.-E., Pihko, H., Guicheney, P., Topaloglu, H.
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<strong>Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci.</strong>
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Neuromusc. Disord. 10: 548-552, 2000.
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[PubMed: 11053680]
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[Full Text: https://doi.org/10.1016/s0960-8966(00)00140-1]
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<p class="mim-text-font">
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Topaloglu, H., Brockington, M., Yuva, Y., Talim, B., Haliloglu, G., Blake, D., Torelli, S., Brown, S. C., Muntoni, F.
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<strong>FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts.</strong>
|
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Neurology 60: 988-992, 2003. Note: Erratum: Neurology 60: 1875, 2003.
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[PubMed: 12654965]
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[Full Text: https://doi.org/10.1212/01.wnl.0000052996.14099.dc]
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</p>
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<p class="mim-text-font">
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van Reeuwijk, J., Olderode-Berends, M. J. W., van den Elzen, C., Brouwer, O. F., Roscioli, T., van Pampus, M. G., Scheffer, H., Brunner, H. G., van Bokhoven, H., Hol, F. A.
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<strong>A homozygous FKRP start codon mutation is associated with Walker-Warburg syndrome, the severe end of the clinical spectrum.</strong>
|
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Clin. Genet. 78: 275-281, 2010.
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[PubMed: 20236121]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01384.x]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 4/21/2014<br>Cassandra L. Kniffin - updated : 3/18/2014<br>Ada Hamosh - updated : 2/7/2013<br>George E. Tiller - updated : 2/8/2011<br>Cassandra L. Kniffin - updated : 11/8/2010<br>Cassandra L. Kniffin - updated : 5/29/2008<br>Cassandra L. Kniffin - updated : 2/12/2008<br>George E. Tiller - updated : 11/8/2007<br>Cassandra L. Kniffin - updated : 3/3/2006<br>Cassandra L. Kniffin - updated : 2/10/2006<br>Cassandra L. Kniffin - updated : 1/12/2006<br>Victor A. McKusick - updated : 2/4/2005<br>George E. Tiller - updated : 9/13/2004<br>Cassandra L. Kniffin - updated : 5/7/2004<br>Cassandra L. Kniffin - updated : 3/17/2004<br>Cassandra L. Kniffin - updated : 10/1/2003<br>Cassandra L. Kniffin - updated : 6/10/2003<br>George E. Tiller - updated : 8/22/2002
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Victor A. McKusick : 1/7/2002
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carol : 08/19/2020<br>carol : 10/08/2019<br>carol : 09/27/2018<br>carol : 09/26/2018<br>carol : 06/08/2018<br>alopez : 12/09/2014<br>alopez : 12/9/2014<br>carol : 10/20/2014<br>mcolton : 10/16/2014<br>carol : 4/23/2014<br>mcolton : 4/22/2014<br>ckniffin : 4/21/2014<br>carol : 3/19/2014<br>ckniffin : 3/18/2014<br>alopez : 2/13/2013<br>alopez : 2/13/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>wwang : 6/13/2011<br>terry : 3/14/2011<br>wwang : 3/11/2011<br>terry : 2/8/2011<br>carol : 11/11/2010<br>carol : 11/10/2010<br>ckniffin : 11/8/2010<br>ckniffin : 12/4/2009<br>wwang : 6/23/2009<br>wwang : 7/2/2008<br>ckniffin : 5/29/2008<br>wwang : 2/20/2008<br>ckniffin : 2/12/2008<br>wwang : 12/3/2007<br>wwang : 11/26/2007<br>terry : 11/8/2007<br>wwang : 8/3/2007<br>ckniffin : 7/24/2007<br>ckniffin : 7/24/2007<br>wwang : 3/10/2006<br>ckniffin : 3/3/2006<br>wwang : 2/20/2006<br>ckniffin : 2/10/2006<br>wwang : 1/18/2006<br>ckniffin : 1/12/2006<br>carol : 2/16/2005<br>ckniffin : 2/15/2005<br>terry : 2/4/2005<br>tkritzer : 9/20/2004<br>tkritzer : 9/13/2004<br>carol : 7/27/2004<br>tkritzer : 5/10/2004<br>ckniffin : 5/7/2004<br>tkritzer : 3/18/2004<br>ckniffin : 3/17/2004<br>terry : 11/10/2003<br>cwells : 11/7/2003<br>carol : 10/3/2003<br>ckniffin : 10/1/2003<br>carol : 6/11/2003<br>ckniffin : 6/10/2003<br>carol : 6/10/2003<br>ckniffin : 5/29/2003<br>ckniffin : 12/27/2002<br>cwells : 8/22/2002<br>joanna : 1/18/2002<br>cwells : 1/14/2002<br>cwells : 1/10/2002
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