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Entry
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- *607440 - FUKUTIN; FKTN
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*607440</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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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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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607440">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000106692;t=ENST00000357998" 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=2218" 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=607440" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000106692;t=ENST00000357998" 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_001079802,NM_001198963,NM_001351496,NM_001351497,NM_001351498,NM_001351499,NM_001351500,NM_001351501,NM_001351502,NM_006731,NR_147213,NR_147214,XM_006717014,XM_011518368,XM_011518369,XM_011518373,XM_011518374,XM_011518379,XM_011518391,XM_017014462,XM_017014475,XM_047422967,XM_047422968,XM_047422969,XM_047422970,XM_047422971,XM_047422972,XM_047422973,XM_047422974,XM_047422975,XM_047422976,XM_047422977,XM_047422978,XM_047422979,XM_047422980,XM_047422981,XM_047422982,XM_047422983,XM_047422984,XM_047422985,XM_047422986,XM_047422987,XM_047422988,XM_047422989,XM_047422990,XM_047422991,XM_047422992,XM_047422993,XM_047422994,XM_047422995,XM_047422996,XM_047422997,XM_047422998,XM_047422999,XM_047423000,XM_047423001,XM_047423002" 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_001079802" 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=607440" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=06308&isoform_id=06308_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/FKTN" 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/3370993,7416856,28381358,75517928,85567121,109730265,109734821,119395712,119395714,119579405,194374753,194385802,312176389,350994325,578817204,767956627,767956629,767956637,767956639,767956649,767956673,1034664387,1034664425,1044329583,1191017936,1191017938,1191017940,1191017942,1191017944,1191017946,1191017948,2217376095,2217376097,2217376099,2217376101,2217376103,2217376105,2217376108,2217376110,2217376112,2217376114,2217376116,2217376118,2217376120,2217376122,2217376124,2217376126,2217376128,2217376130,2217376132,2217376134,2217376136,2217376139,2217376141,2217376143,2217376145,2217376147,2217376149,2217376151,2217376153,2217376155,2217376157,2217376159,2217376162,2217376164,2217376166,2217376169,2462623374,2462623376,2462623378,2462623380,2462623382,2462623384,2462623386,2462623388,2462623390,2462623392,2462623394,2462623396,2462623398,2462623400,2462623402,2462623404,2462623406,2462623408,2462623410,2462623412,2462623414,2462623416,2462623418,2462623420,2462623422,2462623424,2462623426,2462623428,2462623430,2462623432,2462623434,2462623436,2462623438,2462623440,2462623442,2462623444,2462623446,2462623448,2462623450,2462623452,2462623454,2462623456,2462623458,2462623460,2462623462" 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/O75072" 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=2218" 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=ENSG00000106692;t=ENST00000357998" 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=FKTN" 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=FKTN" 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+2218" 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/FKTN" 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:2218" 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/2218" 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=chr9&hgg_gene=ENST00000357998.10&hgg_start=105558130&hgg_end=105641118&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:3622" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/fktn" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607440[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=607440[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/FKTN/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/ENSG00000106692" 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=FKTN" 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=FKTN" 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=FKTN" 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/FKTN" 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=FKTN&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/PA162388669" 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:3622" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2179507" 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/FKTN#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:2179507" 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/2218/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=2218" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00011554;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00011554 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020307;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020307 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020924;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020924 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020927;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020927 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021249;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021249 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-070410-96" 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:2218" 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=FKTN&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> 111502003, 726618007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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607440
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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FUKUTIN; FKTN
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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FCMD GENE; FCMD
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FKTN" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FKTN</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/9/389?start=-3&limit=10&highlight=389">9q31.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:105558130-105641118&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'})">9:105,558,130-105,641,118</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
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Phenotype <br /> MIM number
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9q31.2
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Cardiomyopathy, dilated, 1X
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<a href="/entry/611615"> 611615 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
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<span class="mim-font">
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<a href="/entry/253800"> 253800 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4
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<a href="/entry/613152"> 613152 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4
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<a href="/entry/611588"> 611588 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/607440" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/607440" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<h4>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The FKTN gene encodes a type II transmembrane protein that is targeted to the Golgi apparatus through an N-terminal signal anchor (<a href="#5" 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>). <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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<strong>Cloning and Expression</strong>
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<p>On the basis of haplotype analysis, <a href="#22" class="mim-tip-reference" title="Toda, T., Miyake, M., Kobayashi, K., Mizuno, K., Saito, K., Osawa, M., Nakamura, Y., Kanazawa, I., Nakagome, Y., Yokunaga, K., Nakahori, Y. <strong>Linkage-disequilibrium mapping narrows the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region to less than 100 kb.</strong> Am. J. Hum. Genet. 59: 1313-1320, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940277</a>]" pmid="8940277">Toda et al. (1996)</a> concluded that the locus for Fukuyama congenital muscular dystrophy (FCMD; <a href="/entry/253800">253800</a>) lies within a 100-kb region on chromosome 9q13. By positional cloning, <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> identified the FKTN gene. The deduced 461-amino acid protein, which they termed fukutin, was expressed in various tissues in normal individuals. The predicted protein contains an N-terminal signal sequence which, together with results from transfection experiments, suggested that fukutin is a secreted protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940277+9690476" 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 positional cloning, <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> identified the FKTN gene on chromosome 9q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9690476" 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="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> found evidence of colocalization of fukutin with a Golgi marker and a granular cytoplasmic distribution, suggesting that fukutin passes through the Golgi before being packaged into secretory vesicles. The signal was not seen at the plasma membrane, however, where most proteins responsible for muscular dystrophies are located. <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> suggested that fukutin may be located in the extracellular matrix, where it interacts with and reinforces a large complex encompassing the outside and inside of muscle membranes; alternatively, as a secreted protein, fukutin may cause muscular dystrophy by an unknown mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9690476" 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 Northern blot and RT-PCR analysis, <a href="#17" class="mim-tip-reference" title="Sasaki, J., Ishikawa, K., Kobayashi, K., Kondo-Iida, E., Fukayama, M., Mizusawa, H., Takashima, S., Sakakihara, Y., Nakamura, Y., Toda, T. <strong>Neuronal expression of the fukutin gene.</strong> Hum. Molec. Genet. 9: 3083-3090, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11115853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11115853</a>] [<a href="https://doi.org/10.1093/hmg/9.20.3083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11115853">Sasaki et al. (2000)</a> determined that the fukutin gene is expressed at similar levels in control fetal and adult brain, but is much reduced in FCMD brains. Tissue in situ hybridization analysis revealed fukutin mRNA expression in migrating neurons, including Cajar-Retzius cells and adult cortical neurons, as well as hippocampal pyramidal cells and cerebellar Purkinje cells. However, no expression was observed in the glia limitans, the subpial astrocytes (which contribute to basement membrane formation), or other glial cells. In the FCMD brain, neurons in regions with no dysplasia showed fair expression, whereas transcripts were nearly undetectable in the overmigrated dysplastic region. The authors hypothesized that fukutin may influence neuronal migration itself rather than formation of the basement membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11115853" 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>Alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) is a cell surface protein that plays an important role in the assembly of the extracellular matrix in muscle, brain, and peripheral nerves by linking the basal lamina to cytoskeletal proteins. Using PCR, immunohistochemistry, and immunoblotting to analyze samples from patients with FCMD, <a href="#8" class="mim-tip-reference" title="Hayashi, Y. K., Ogawa, M., Tagawa, K., Noguchi, S., Ishihara, T., Nonaka, I., Arahata, K. <strong>Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.</strong> Neurology 57: 115-121, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11445638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11445638</a>] [<a href="https://doi.org/10.1212/wnl.57.1.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11445638">Hayashi et al. (2001)</a> confirmed a deficiency of fukutin and found marked deficiency of highly glycosylated DAG1 in skeletal and cardiac muscle and reduced amounts of DAG1 in brain tissue. Beta-dystroglycan (see <a href="/entry/128239">128239</a>) was normal in all tissues examined. These findings supported the suggestion that fukutin deficiency affects the modification of glycosylation of DAG1, which then cannot localize or function properly and may be degraded or eluted from the extracellular surface membrane of the muscle fiber. <a href="#8" class="mim-tip-reference" title="Hayashi, Y. K., Ogawa, M., Tagawa, K., Noguchi, S., Ishihara, T., Nonaka, I., Arahata, K. <strong>Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.</strong> Neurology 57: 115-121, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11445638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11445638</a>] [<a href="https://doi.org/10.1212/wnl.57.1.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11445638">Hayashi et al. (2001)</a> concluded that this disruption underlies the developmental, structural, and functional damage to muscles in patients with FCMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11445638" 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="#5" 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 fukutin and fukutin-related protein (FKRP; <a href="/entry/606596">606596</a>) are Golgi-resident proteins and that they 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><strong><em>Muscular Dystrophy-Dystroglycanopathy, Types A4, B4, and C4</em></strong></p><p>
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Mutation in the FKTN gene can cause 3 different forms of muscular dystrophy-dystroglycanopathy (MDDG): a severe congenital form with brain and eye anomalies (type A4; MDDGA4, <a href="/entry/253800">253800</a>), formerly designated Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), or muscle-eye-brain disease (MEB); a less severe congenital form without impaired intellectual development (type B4; MDDGB4; <a href="/entry/613152">613152</a>); and a milder limb-girdle form (type C4; MDDGC4; <a href="/entry/611588">611588</a>), also designated LGMDR13 and LGMD2M.</p><p>In Japan, <a href="#22" class="mim-tip-reference" title="Toda, T., Miyake, M., Kobayashi, K., Mizuno, K., Saito, K., Osawa, M., Nakamura, Y., Kanazawa, I., Nakagome, Y., Yokunaga, K., Nakahori, Y. <strong>Linkage-disequilibrium mapping narrows the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region to less than 100 kb.</strong> Am. J. Hum. Genet. 59: 1313-1320, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940277</a>]" pmid="8940277">Toda et al. (1996)</a> and <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> described a haplotype that is shared by more than 80% of chromosomes of patients with Fukuyama congenital muscular dystrophy (FCMD; MDDGA4), indicating that most chromosomes bearing the mutation could be derived from a single ancestor. <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> reported that there is a retrotransposal insertion (<a href="#0001">607440.0001</a>) of tandemly repeated sequences within the candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence was about 3 kb long and was located in the 3-prime untranslated region (UTR) of the gene. One component of the 3,062-bp insert was a SINE (short interspersed sequence)-type retroposon sequence. <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> stated that FCMD is the first human disease known to be caused by an ancient retrotransposal integration. In patients with FCMD, <a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> identified 2 independent mutations (<a href="#0002">607440.0002</a> and <a href="#0003">607440.0003</a>) in the FKTN gene. <a href="#24" class="mim-tip-reference" title="Watanabe, M., Kobayashi, K., Jin, F., Park, K. S., Yamada, T., Tokunaga, K., Toda, T. <strong>Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations.</strong> Am. J. Med. Genet. 138A: 344-348, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16222679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16222679</a>] [<a href="https://doi.org/10.1002/ajmg.a.30978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16222679">Watanabe et al. (2005)</a> noted that the insertion was of a class of retroposon referred to as SINE-VNTR-Alu (SVA). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940277+16222679+9690476" 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="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a> extended the known mutation repertoire of the FKTN gene. In a systematic analysis of the FKTN gene in 107 unrelated patients with FCMD, they found 4 novel nonfounder mutations in 5 patients: 1 missense, 1 nonsense, 1 L1 insertion (<a href="#0004">607440.0004</a>), and one 1-bp insertion (<a href="#0005">607440.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545611" 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 patients with a clinical diagnosis of Walker-Warburg syndrome (MDDGA4), <a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., van Bokhoven, H., van Beusekom, E., Van den Akker, W., Kant, S., Dobyns, W. B., Cormand, B., Currier, S., Hamel, B., Talim, B., Topaloglu, H., Brunner, H. G. <strong>A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype.</strong> J. Med. Genet. 40: 845-848, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627679</a>] [<a href="https://doi.org/10.1136/jmg.40.11.845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14627679">Beltran-Valero de Bernabe et al. (2003)</a> and <a href="#18" class="mim-tip-reference" title="Silan, F., Yoshioka, M., Kobayashi, K., Simsek, E., Tunc, M., Alper, M., Cam, M., Guven, A., Fukuda, Y., Kinoshita, M., Kocabay, K., Toda, T. <strong>A new mutation of the fukutin gene in a non-Japanese patient.</strong> Ann. Neurol. 53: 392-396, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601708</a>] [<a href="https://doi.org/10.1002/ana.10491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601708">Silan et al. (2003)</a> independently identified mutations in the FKTN gene (<a href="#0006">607440.0006</a> and <a href="#0007">607440.0007</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12601708+14627679" 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 cell lines from unrelated Ashkenazi Jewish parents and their son, who was diagnosed with WWS, <a href="#4" class="mim-tip-reference" title="Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J. <strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong> Clin. Genet. 73: 139-145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18177472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18177472</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18177472">Cotarelo et al. (2008)</a> identified the 1-bp insertion in the FKTN gene (<a href="#0005">607440.0005</a>) that had previously been identified in compound heterozygosity in patients with FCMD and FKTN-related muscular dystrophy. The son was homozygous for the insertion, and the unaffected parents were heterozygous carriers. In a Spanish female infant diagnosed with WWS who died at day 5 of life, <a href="#4" class="mim-tip-reference" title="Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J. <strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong> Clin. Genet. 73: 139-145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18177472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18177472</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18177472">Cotarelo et al. (2008)</a> identified compound heterozygosity for a missense mutation (G125S; <a href="#0012">607440.0012</a>) and a 473-bp deletion (<a href="#0013">607440.0013</a>) in the FKTN gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18177472" 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 3 patients with limb-girdle muscular dystrophy due to defective glycosylation of dystroglycan (MDDGC4; <a href="/entry/611588">611588</a>), <a href="#7" class="mim-tip-reference" title="Godfrey, C., Escolar, D., Brockington, M., Clement, E. M., Mein, R., Jimenez-Mallebrera, C., Torelli, S., Feng, L., Brown, S. C., Sewry, C. A., Rutherford, M., Shapira, Y., Abbs, S., Muntoni, F. <strong>Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.</strong> Ann. Neurol. 60: 603-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044012</a>] [<a href="https://doi.org/10.1002/ana.21006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17044012">Godfrey et al. (2006)</a> identified compound heterozygosity for mutations in the FKTN gene (<a href="#0005">607440.0005</a>; <a href="#0008">607440.0008</a>; <a href="#0009">607440.0009</a>). The authors noted that the phenotype was much less severe than that observed in the allelic disorder Fukuyama congenital muscular dystrophy. The patients showed early-onset proximal muscular dystrophy, normal intelligence and brain structure, and favorable response to steroid treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17044012" 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="Puckett, R. L., Moore, S. A., Winder, T. L., Willer, T., Romansky, S. G., Covault, K. K., Campbell, K. P., Abdenur, J. E. <strong>Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.</strong> Neuromusc. Disord. 19: 352-356, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342235[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.nmd.2009.03.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19342235">Puckett et al. (2009)</a> identified compound heterozygous mutations in the FKTN gene (A114T, <a href="#0014">607440.0014</a> and F176S, <a href="#0015">607440.0015</a>) in 2 brothers of Japanese and Caucasian ancestry with FKTN-related limb-girdle muscular dystrophy (MDDGC4). The phenotype was relatively mild, and there was no cardiac or cognitive involvement. Skeletal muscle biopsy showed defective glycosylation of alpha-dystroglycan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19342235" 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="Godfrey, C., Clement, E., Mein, R., Brockington, M., Smith, J., Talim, B., Straub, V., Robb, S., Quinlivan, R., Feng, L., Jimenez-Mallebrera, C., Mercuri, E., and 10 others. <strong>Refining genotype-phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.</strong> Brain 130: 2725-2735, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878207</a>] [<a href="https://doi.org/10.1093/brain/awm212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878207">Godfrey et al. (2007)</a> identified FKTN mutations in 6 of 92 patients with evidence of a muscular dystrophy due to defective glycosylation of alpha-dystroglycan. Only 2 had structural brain anomalies: 1 with WWS and 1 with MEB. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17878207" 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="#13" 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 compound heterozygosity for 2 mutations in the FKTN gene (R307Q; <a href="#0009">607440.0009</a> and 42delG; <a href="#0019">607440.0019</a>) in 1 of 81 Italian patients with congenital muscular dystrophy associated with defective glycosylation of alpha-dystroglycan (MDDGB4; <a href="/entry/613152">613152</a>). The patient did not have mental retardation and had no structural brain abnormalities. <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><p><a href="#21" class="mim-tip-reference" title="Taniguchi-Ikeda, M., Kobayashi, K., Kanagawa, M., Yu, C., Mori, K., Oda, T., Kuga, A., Kurahashi, H., Akman, H. O., DiMauro, S., Kaji, R., Yokota, T., Takeda, S., Toda, T. <strong>Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.</strong> Nature 478: 127-131, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21979053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21979053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21979053[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21979053">Taniguchi-Ikeda et al. (2011)</a> demonstrated that aberrant mRNA splicing, induced by SINE-VNTR-Alu (SVA) exon trapping, underlies the molecular pathogenesis of FCMD (MDDGA4). Quantitative mRNA analysis pinpointed a region that was missing from transcripts in patients with FCMD. This region spans part of the 3-prime end of the fukutin coding region, a proximal part of the 3-prime UTR, and the SVA insertion. Correspondingly, fukutin mRNA transcripts in patients with FCMD and SVA knockin model mice were shorter than the expected length. Sequence analysis revealed an abnormal splicing event, provoked by a strong acceptor site in SVA and a rare alternative donor site in fukutin exon 10. The resulting product truncates the fukutin carboxy terminus and adds 129 amino acids encoded by the SVA. Introduction of antisense oligonucleotides targeting the splice acceptor, the predicted exonic splicing enhancer, and the intronic splicing enhancer prevented pathogenic exon trapping by SVA in cells of patients with FCMD and model mice, rescuing normal fukutin mRNA expression and protein production. Antisense oligonucleotide treatment also restored fukutin functions, including O-glycosylation of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) and laminin (see <a href="/entry/156225">156225</a>) binding by alpha-dystroglycan. Moreover, <a href="#21" class="mim-tip-reference" title="Taniguchi-Ikeda, M., Kobayashi, K., Kanagawa, M., Yu, C., Mori, K., Oda, T., Kuga, A., Kurahashi, H., Akman, H. O., DiMauro, S., Kaji, R., Yokota, T., Takeda, S., Toda, T. <strong>Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.</strong> Nature 478: 127-131, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21979053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21979053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21979053[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21979053">Taniguchi-Ikeda et al. (2011)</a> observed exon trapping in other SVA insertions associated with disease (hypercholesterolemia, neutral lipid storage disease) and human-specific SVA insertion in a novel gene. Thus, <a href="#21" class="mim-tip-reference" title="Taniguchi-Ikeda, M., Kobayashi, K., Kanagawa, M., Yu, C., Mori, K., Oda, T., Kuga, A., Kurahashi, H., Akman, H. O., DiMauro, S., Kaji, R., Yokota, T., Takeda, S., Toda, T. <strong>Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.</strong> Nature 478: 127-131, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21979053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21979053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21979053[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21979053">Taniguchi-Ikeda et al. (2011)</a> concluded that, although splicing into SVA is known, they had discovered in human disease a role for SVA-mediated exon trapping, and demonstrated the promise of splicing modulation therapy as the first radical clinical treatment for FCMD and other SVA-mediated diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21979053" 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 human mutant FKTN constructs with expression in mouse myoblasts, <a href="#19" class="mim-tip-reference" title="Tachikawa, M., Kanagawa, M., Yu, C.-C., Kobayashi, K., Toda, T. <strong>Mislocalization of fukutin protein by disease-causing missense mutations can be rescued with treatments directed at folding amelioration.</strong> J. Biol. Chem. 287: 8398-8406, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22275357[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/10.1074/jbc.M111.300905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275357">Tachikawa et al. (2012)</a> found that 4 pathogenic missense mutations (A170E, <a href="#0016">607440.0016</a>; H172R; H186R; and Y371C, <a href="#0017">607440.0017</a>) showed aberrant accumulation in the endoplasmic reticulum (ER) due to protein misfolding and failure of the anterograde pathway, in contrast to wildtype FKTN, which localized to the Golgi apparatus. The POMGNT1 (<a href="/entry/606822">606822</a>) protein also mislocalized to the ER when coexpressed with mutant FKTN. Low-temperature culture or treatment with curcumin variably corrected the subcellular localization of the missense mutant proteins. Expression studies in Fktn-null mouse embryonic cells showed that the mutant proteins retained normal glycosylation activity, indicating that some disease-causing mutations are pathogenic due to abnormal folding and localization. The findings suggested a therapeutic strategy for certain FKTN mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Dilated Cardiomyopathy 1X</em></strong></p><p>
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<a href="#14" class="mim-tip-reference" title="Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y., Ogino, M., Takada, F., Eriguchi, M., Kotooka, N., Campbell, K. P., Osawa, M., Nishino, I. <strong>Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.</strong> Ann. Neurol. 60: 597-602, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17036286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17036286</a>] [<a href="https://doi.org/10.1002/ana.20973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17036286">Murakami et al. (2006)</a> analyzed the FKTN gene in 6 Japanese patients with CMD and mild or no limb-girdle muscle involvement (CMD1X; <a href="/entry/611615">611615</a>) and identified compound heterozygosity in all for a 3-kb retrotransposal insertion (<a href="#0001">607440.0001</a>) and another missense mutation (<a href="#0010">607440.0010</a> or <a href="#0011">607440.0011</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17036286" 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="#12" class="mim-tip-reference" title="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a> noted that the frequency of severe phenotypes, including Walker-Warburg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and a founder mutation on the other, than among probands who were homozygous for the 3-kb retrotransposon (<a href="#0001">607440.0001</a>). Remarkably, they detected no FCMD patients with nonfounder (point) mutations on both alleles of the gene, suggesting that such cases might be embryonic lethal. This could explain why few FCMD cases are reported in non-Japanese populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545611" 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 Turkish patient with a severe phenotype that resembled Walker-Warburg syndrome, <a href="#18" class="mim-tip-reference" title="Silan, F., Yoshioka, M., Kobayashi, K., Simsek, E., Tunc, M., Alper, M., Cam, M., Guven, A., Fukuda, Y., Kinoshita, M., Kocabay, K., Toda, T. <strong>A new mutation of the fukutin gene in a non-Japanese patient.</strong> Ann. Neurol. 53: 392-396, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601708</a>] [<a href="https://doi.org/10.1002/ana.10491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601708">Silan et al. (2003)</a> identified a homozygous nonfounder mutation in the FKTN gene (<a href="#0006">607440.0006</a>). The patient died at 10 days of age. The authors noted that this was the first non-Japanese patient to be reported with a fukutin mutation, and that the mutation was the first reported nonfounder homozygous mutation. <a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., van Bokhoven, H., van Beusekom, E., Van den Akker, W., Kant, S., Dobyns, W. B., Cormand, B., Currier, S., Hamel, B., Talim, B., Topaloglu, H., Brunner, H. G. <strong>A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype.</strong> J. Med. Genet. 40: 845-848, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627679</a>] [<a href="https://doi.org/10.1136/jmg.40.11.845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14627679">Beltran-Valero de Bernabe et al. (2003)</a> reported a similar case (see <a href="#0007">607440.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12601708+14627679" 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>To establish a genotype-phenotype correlation, <a href="#16" class="mim-tip-reference" title="Saito, K., Osawa, M., Wang, Z.-P., Ikeya, K., Fukuyama, Y., Kondo-Iida, E., Toda, T., Ohashi, H., Kurosawa, K., Wakai, S., Kaneko, K. <strong>Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy.</strong> Am. J. Med. Genet. 92: 184-190, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10817652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10817652</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000529)92:3<184::aid-ajmg5>3.0.co;2-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10817652">Saito et al. (2000)</a> performed haplotype analysis using microsatellite markers closest to the FKTN gene in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 probands with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder haplotype, whereas the other 2 were heterozygous for the haplotype. Of the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmologic abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype were heterozygous for the ancestral founder haplotype, and the other 1 homozygous for the haplotype. <a href="#16" class="mim-tip-reference" title="Saito, K., Osawa, M., Wang, Z.-P., Ikeya, K., Fukuyama, Y., Kondo-Iida, E., Toda, T., Ohashi, H., Kurosawa, K., Wakai, S., Kaneko, K. <strong>Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy.</strong> Am. J. Med. Genet. 92: 184-190, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10817652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10817652</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000529)92:3<184::aid-ajmg5>3.0.co;2-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10817652">Saito et al. (2000)</a> confirmed that at least 1 chromosome in each of the 56 FCMD patients had the ancestral founder haplotype. The rate of heterozygosity for this haplotype was significantly higher in severe cases than in typical or mild cases (P less than 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10817652" 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="#20" class="mim-tip-reference" title="Takeda, S., Kondo, M., Sasaki, J., Kurahashi, H., Kano, H., Arai, K., Misaki, K., Fukui, T., Kobayashi, K., Tachikawa, M., Imamura, M., Nakamura, Y., Shimizu, T., Murakami, T., Sunada, Y., Fujikado, T., Matsumura, K., Terashima, T., Toda, T. <strong>Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development.</strong> Hum. Molec. Genet. 12: 1449-1459, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12783852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12783852</a>] [<a href="https://doi.org/10.1093/hmg/ddg153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12783852">Takeda et al. (2003)</a> reported that chimeric mice generated using embryonic stem cells targeted for both fukutin alleles developed severe muscular dystrophy, with the selective deficiency of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) and its laminin (see <a href="/entry/156225">156225</a>)-binding activity. In addition, these mice showed laminar disorganization of the cortical structures in the brain with impaired laminin assembly, focal interhemispheric fusion, and hippocampal and cerebellar dysgenesis. Further, chimeric mice showed anomaly of the lens, loss of laminar structure in the retina, and retinal detachment. The authors concluded that fukutin is necessary for the maintenance of muscle integrity, cortical histiogenesis, and normal ocular development, and suggested a functional linkage between fukutin and alpha-dystroglycan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12783852" 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="#9" class="mim-tip-reference" title="Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Miyagoe-Suzuki, Y., Wang, F., Fujikake, N., Taniguchi, M., Lu, Z., Tachikawa, M., Nagai, Y., Tashiro, F., Miyazaki, J., Tajima, Y., Takeda, S., Endo, T., Kobayashi, K., Campbell, K. P., Toda, T. <strong>Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.</strong> Hum. Molec. Genet. 18: 621-631, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19017726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19017726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19017726[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/ddn387" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19017726">Kanagawa et al. (2009)</a> generated a mouse model of FCMD by introducing the disease-causing retrotransposon into the mouse Fktn gene. Knockin mice exhibited hypoglycosylated alpha-dystroglycan; however, no signs of muscular dystrophy were observed. More sensitive methods detected minor levels of intact alpha-dystroglycan, and solid-phase assays determined laminin-binding levels to be 50% of normal. In contrast, intact alpha-dystroglycan was undetectable in the dystrophic Large(myd) mouse (see <a href="/entry/603590">603590</a>), and laminin-binding activity was markedly reduced. This suggested that a small amount of intact alpha-dystroglycan may be sufficient to maintain muscle cell integrity in knockin mice. Transfer of fukutin into knockin mice restored glycosylation of alpha-dystroglycan. Transfer of LARGE produced laminin-binding forms of alpha-dystroglycan in both knockin mice and the Pomgnt1 (<a href="/entry/606822">606822</a>)-mutant mouse, which is another model of dystroglycanopathy. <a href="#9" class="mim-tip-reference" title="Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Miyagoe-Suzuki, Y., Wang, F., Fujikake, N., Taniguchi, M., Lu, Z., Tachikawa, M., Nagai, Y., Tashiro, F., Miyazaki, J., Tajima, Y., Takeda, S., Endo, T., Kobayashi, K., Campbell, K. P., Toda, T. <strong>Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.</strong> Hum. Molec. Genet. 18: 621-631, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19017726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19017726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19017726[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/ddn387" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19017726">Kanagawa et al. (2009)</a> suggested that even partial restoration of alpha-dystroglycan glycosylation and laminin-binding activity by replacing or augmenting glycosylation-related genes may effectively deter dystroglycanopathy progression and thus provide therapeutic benefits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19017726" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>19 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=607440[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 WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000003351 OR RCV000003352" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003351, RCV000003352" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003351...</a>
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<p><strong><em>Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A, 4</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> found that 87% of mutant alleles causing the autosomal recessive disorder Fukuyama congenital muscular dystrophy (MDDGA4; <a href="/entry/253800">253800</a>) carried an insertion of a 3,062-bp transposon, situated in the 3-prime UTR of the FKTN gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9690476" 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>Most Japanese patients with the retrotransposal insertion in the FKTN gene share a common founder haplotype. By applying 2 methods for the study of linkage disequilibrium between flanking polymorphic markers and the disease locus, and of its decay over time, <a href="#3" class="mim-tip-reference" title="Colombo, R., Bignamini, A. A., Carobene, A., Sasaki, J., Tachikawa, M., Kobayashi, K., Toda, T. <strong>Age and origin of the FCMD 3-prime-untranslated-region retrotransposal insertion mutation causing Fukuyama-type congenital muscular dystrophy in the Japanese population.</strong> Hum. Genet. 107: 559-567, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153909</a>] [<a href="https://doi.org/10.1007/s004390000421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153909">Colombo et al. (2000)</a> calculated the age of the insertion mutation to be approximately 102 generations (95% CI: 86-117 g), or slightly less. The estimated age dates the most recent common ancestor of the mutation-bearing chromosomes back to the time (or a few centuries before) the Yayoi people began migrating to Japan from the Korean peninsula. FCMD was the first human disease known to be caused primarily by an ancient retrotransposal integration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153909" 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="Kato, R., Kawamura, J., Sugawara, H., Niikawa, N., Matsumoto, N. <strong>A rapid diagnostic method for a retrotransposal insertional mutation into the FCMD gene in Japanese patients with Fukuyama congenital muscular dystrophy.</strong> Am. J. Med. Genet. 127A: 54-57, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15103718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15103718</a>] [<a href="https://doi.org/10.1002/ajmg.a.20669" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15103718">Kato et al. (2004)</a> stated that 9 nonfounder mutations had been identified in Japanese FCMD patients. Severe phenotype was significantly more frequent in patients who were compound heterozygotes for a point mutation and the 3-kb founder insertion in the FKTN gene than in homozygotes for the founder mutation. The authors described a PCR-based diagnostic method for rapid detection of the insertion mutation. Using this method, they screened 18 FCMD patients and found 16 homozygotes and 2 heterozygotes for the insertion. In the general Japanese population, they found that 6 of 676 persons were heterozygous carriers. Furthermore, they found 3 homozygotes for the FCMD founder mutation among 97 patients who had been said to have probable Duchenne muscular dystrophy (<a href="/entry/310200">310200</a>) or Becker muscular dystrophy (<a href="/entry/300376">300376</a>) (DMD/BMD) without any mutation in the DMD gene (<a href="/entry/300377">300377</a>). On the other hand, there were no FCMD homozygotes but 4 heterozygous carriers among 335 patients with DMD mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15103718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By sequence analysis, <a href="#24" class="mim-tip-reference" title="Watanabe, M., Kobayashi, K., Jin, F., Park, K. S., Yamada, T., Tokunaga, K., Toda, T. <strong>Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations.</strong> Am. J. Med. Genet. 138A: 344-348, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16222679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16222679</a>] [<a href="https://doi.org/10.1002/ajmg.a.30978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16222679">Watanabe et al. (2005)</a> characterized the insertion mutation and found that it was enclosed by target-site duplications at both ends. They noted that the sequence motif was characteristic of a class of retroposon referred to as SINE-VNTR-Alu (SVA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16222679" 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="#24" class="mim-tip-reference" title="Watanabe, M., Kobayashi, K., Jin, F., Park, K. S., Yamada, T., Tokunaga, K., Toda, T. <strong>Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations.</strong> Am. J. Med. Genet. 138A: 344-348, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16222679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16222679</a>] [<a href="https://doi.org/10.1002/ajmg.a.30978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16222679">Watanabe et al. (2005)</a> established a rapid PCR-based diagnostic method using 3 primers simultaneously in order to detect the 3,062-bp retrotransposal insertion. Fifteen founder chromosomes were detected among 2,814 Japanese individuals. Heterozygous carriers were identified in various regions throughout Japan, with a carrier frequency of approximately 1 in 188. The insertion mutation was found in 1 in 935 Korean individuals but not among 203 Mongolians and 766 mainland Chinese, suggesting that FCMD carriers are rare outside of Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16222679" 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="#25" class="mim-tip-reference" title="Xiong, H., Wang, S., Kobayashi, K., Jiang, Y., Wang, J., Chang, X., Yuan, Y., Liu, J., Toda, T., Fukuyama, Y., Wu, X. <strong>Fukutin gene retrotransposal insertion in a non-Japanese Fukuyama congenital muscular dystrophy (FCMD) patient.</strong> Am. J. Med. Genet. 149A: 2403-2408, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19842201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19842201</a>] [<a href="https://doi.org/10.1002/ajmg.a.33057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19842201">Xiong et al. (2009)</a> reported a Chinese boy with FCMD who was compound heterozygous for 2 mutations in the fukutin gene: the common 3-kb retroposon insertion and R47X (<a href="#0002">607440.0002</a>). Although the boy's parents were born in Henan and Shanxi Provinces and had no known Japanese ancestry, haplotype analysis showed that both mutant alleles were on Japanese-derived haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19842201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cardiomyopathy, Dilated, 1X</em></strong></p><p>
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In 6 Japanese patients from 4 families with dilated cardiomyopathy and mild or no limb-girdle involvement (CMD1X; <a href="/entry/611615">611615</a>), <a href="#14" class="mim-tip-reference" title="Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y., Ogino, M., Takada, F., Eriguchi, M., Kotooka, N., Campbell, K. P., Osawa, M., Nishino, I. <strong>Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.</strong> Ann. Neurol. 60: 597-602, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17036286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17036286</a>] [<a href="https://doi.org/10.1002/ana.20973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17036286">Murakami et al. (2006)</a> identified compound heterozygosity in all for the 3-kb retroposon insertion and another missense mutation: Q358P (<a href="#0010">607440.0010</a>) or R179T (<a href="#0011">607440.0011</a>), respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17036286" 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 WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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> rs119463990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463990;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/rs119463990?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=rs119463990" 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=rs119463990" 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="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> searched for inactivating mutations in the FKTN gene in patients with Fukuyama congenital muscular dystrophy (MDDGA4; <a href="/entry/253800">253800</a>) lacking the haplotype indicative of the 3-kb insertion (<a href="#0001">607440.0001</a>) on 1 chromosome. In a total of 6 families, the noninsertion-bearing chromosome showed a nonsense mutation in the FKTN gene: a C-to-T transition at base 250, resulting in premature termination (CGA to TGA; arg47 to ter). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9690476" 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="#11" class="mim-tip-reference" title="Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T. <strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong> Nature 394: 388-392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9690476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9690476</a>] [<a href="https://doi.org/10.1038/28653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9690476">Kobayashi et al. (1998)</a> found that a girl with Fukuyama congenital muscular dystrophy (MDDGA4; <a href="/entry/253800">253800</a>) had inherited the common retrotransposal insertion mutation (<a href="#0001">607440.0001</a>) from her Japanese mother and a 2-bp deletion at bases 298-299 (codon 63), causing a frameshift and a premature stop at codon 75, from her American father (of English and German extraction). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9690476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
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<p>In 2 unrelated patients with unusually severe FCMD (MDDGA4; <a href="/entry/253800">253800</a>), <a href="#12" class="mim-tip-reference" title="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a> detected a 1.2-kb L1 insertion in the FKTN gene. Each patient carried the founder 3-kb retrotransposal insertion (<a href="#0001">607440.0001</a>) on one allele and a distinctive haplotype on the other. Sequence analysis revealed that the 3-prime region of an L1 repetitive element had been inserted 24 basepairs before the intron 7-exon 8 boundary. The patients' RNA was tested for the effects of the insertion by means of reverse transcriptase-PCR analysis, using primers that amplified exons 5-10. Products of various sizes were obtained, suggesting exon skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545611" 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 (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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">rs398123555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398123555;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=rs398123555" 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=rs398123555" 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=RCV000003356 OR RCV000003357 OR RCV000079427 OR RCV000634081 OR RCV000778871 OR RCV002326661 OR RCV003466792 OR RCV005003318" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003356, RCV000003357, RCV000079427, RCV000634081, RCV000778871, RCV002326661, RCV003466792, RCV005003318" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003356...</a>
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<p>In a girl with severe FCMD (MDDGA4; <a href="/entry/253800">253800</a>) including microphthalmia, <a href="#12" class="mim-tip-reference" title="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a> identified a 1-bp insertion (1279insA) in exon 9 of the FKTN gene, causing a frameshift and a premature stop at codon 403. The patient carried the founder insertion (<a href="#0001">607440.0001</a>) from her mother; however, the 1-bp insertion could not be detected in the father by either SSCP or by direct sequencing, leading <a href="#12" class="mim-tip-reference" title="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a> to conclude that this was the first example of a de novo mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545611" 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 cell line from an Ashkenazi Jewish male diagnosed with Walker-Warburg syndrome (MDDGA4), <a href="#4" class="mim-tip-reference" title="Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J. <strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong> Clin. Genet. 73: 139-145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18177472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18177472</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18177472">Cotarelo et al. (2008)</a> identified homozygosity for a 1-bp insertion within a stretch of 6 adenine residues in exon 9 (1160_1168insA). Cell lines from the unrelated, unaffected parents revealed that they were heterozygous carriers of the insertion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18177472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs and an unrelated child with FKTN-related limb-girdle muscular dystrophy (MDDGC4; <a href="/entry/611588">611588</a>), <a href="#7" class="mim-tip-reference" title="Godfrey, C., Escolar, D., Brockington, M., Clement, E. M., Mein, R., Jimenez-Mallebrera, C., Torelli, S., Feng, L., Brown, S. C., Sewry, C. A., Rutherford, M., Shapira, Y., Abbs, S., Muntoni, F. <strong>Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.</strong> Ann. Neurol. 60: 603-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044012</a>] [<a href="https://doi.org/10.1002/ana.21006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17044012">Godfrey et al. (2006)</a> identified compound heterozygosity for mutations in the FKTN gene. All 3 children had a 1-bp insertion in exon 9 (1167insA), which the authors stated was the same mutation as that identified by <a href="#12" class="mim-tip-reference" title="Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T. <strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong> Hum. Molec. Genet. 8: 2303-2309, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545611</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545611">Kondo-Iida et al. (1999)</a>. The insertion was predicted to result in a frameshift at phe390 and premature termination, followed by nonsense-mediated decay of the mRNA transcript. The second mutant allele identified was a 1-bp deletion (<a href="#0008">607440.0008</a>) in 1 child and a missense mutation (R307Q; <a href="#0009">607440.0009</a>) in 2 sibs. The patients showed early-onset proximal muscular dystrophy, normal intelligence and brain structure, and favorable response to steroid treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17044012+10545611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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">rs587777748 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777748;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=rs587777748" 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=rs587777748" 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=RCV000003359 OR RCV001851611 OR RCV004566676" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003359, RCV001851611, RCV004566676" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003359...</a>
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<p>In a Turkish patient with a severe congenital muscular dystrophy phenotype most closely resembling Walker-Warburg syndrome (MDDGA4; <a href="/entry/253800">253800</a>), <a href="#18" class="mim-tip-reference" title="Silan, F., Yoshioka, M., Kobayashi, K., Simsek, E., Tunc, M., Alper, M., Cam, M., Guven, A., Fukuda, Y., Kinoshita, M., Kocabay, K., Toda, T. <strong>A new mutation of the fukutin gene in a non-Japanese patient.</strong> Ann. Neurol. 53: 392-396, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601708</a>] [<a href="https://doi.org/10.1002/ana.10491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601708">Silan et al. (2003)</a> identified a homozygous 1-bp insertion (504insT) in exon 5 of the FKTN gene. The first-cousin parents and an unaffected brother were heterozygous for the mutation. The patient presented at birth with hypotonia, hydrocephalus, respiratory difficulties, ocular abnormalities, and elevated muscle enzymes, and died on the tenth day of life. Postmortem examination revealed severe malformations of the central nervous system, including agyria and cortical disorganization, and congenital muscular dystrophy. <a href="#18" class="mim-tip-reference" title="Silan, F., Yoshioka, M., Kobayashi, K., Simsek, E., Tunc, M., Alper, M., Cam, M., Guven, A., Fukuda, Y., Kinoshita, M., Kocabay, K., Toda, T. <strong>A new mutation of the fukutin gene in a non-Japanese patient.</strong> Ann. Neurol. 53: 392-396, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601708</a>] [<a href="https://doi.org/10.1002/ana.10491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601708">Silan et al. (2003)</a> noted that this was the first reported case of a fukutin mutation found outside the Japanese population and the first reported case of a homozygous nonfounder mutation, which was believed to be embryonic lethal. Although the patient may be considered to have Fukuyama congenital muscular dystrophy because of the mutation in the FKTN gene, the authors noted that classification of the disease in this patient may be difficult because the phenotype is slightly different and resembles Walker-Warburg syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601708" 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 BRAIN AND EYE ANOMALIES), TYPE A, 4</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> rs119463991 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463991;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/rs119463991?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=rs119463991" 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=rs119463991" 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 Turkish patient diagnosed with Walker-Warburg syndrome (MDDGA4; <a href="/entry/253800">253800</a>), <a href="#2" class="mim-tip-reference" title="Beltran-Valero de Bernabe, D., van Bokhoven, H., van Beusekom, E., Van den Akker, W., Kant, S., Dobyns, W. B., Cormand, B., Currier, S., Hamel, B., Talim, B., Topaloglu, H., Brunner, H. G. <strong>A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype.</strong> J. Med. Genet. 40: 845-848, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627679</a>] [<a href="https://doi.org/10.1136/jmg.40.11.845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14627679">Beltran-Valero de Bernabe et al. (2003)</a> identified a homozygous gln116-to-ter (Q116X) mutation in the FKTN gene. Born to second-degree consanguineous parents, the patient had macrocephaly, abnormal eyes, severe hypotonia, and severe brain malformations, including hydrocephalus, agyria/pachygyria, absent corpus callosum and cerebellar vermis, and white matter hyperlucencies. The authors noted that the phenotype in this patient was more consistent with Walker-Warburg syndrome than with Fukuyama congenital muscular dystrophy, and established a genotype/phenotype correlation for fukutin mutations that cause complete loss of protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14627679" 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 (LIMB-GIRDLE), TYPE C, 4</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">rs587777814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777814;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=rs587777814" 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=rs587777814" 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=RCV000003361" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003361" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003361</a>
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<p>In a patient with FKTN-related limb-girdle muscular dystrophy and normal intelligence (MDDGC4; <a href="/entry/611588">611588</a>), <a href="#7" class="mim-tip-reference" title="Godfrey, C., Escolar, D., Brockington, M., Clement, E. M., Mein, R., Jimenez-Mallebrera, C., Torelli, S., Feng, L., Brown, S. C., Sewry, C. A., Rutherford, M., Shapira, Y., Abbs, S., Muntoni, F. <strong>Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.</strong> Ann. Neurol. 60: 603-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044012</a>] [<a href="https://doi.org/10.1002/ana.21006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17044012">Godfrey et al. (2006)</a> identified compound heterozygosity a 1-bp deletion (1363delG) in exon 10 of the FKTN gene, resulting in a frameshift at asp455 and premature termination, and a 1-bp insertion (<a href="#0005">607440.0005</a>). Functional expression studies showed that the 1363delG mutant protein was expressed and localized correctly within the cell. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17044012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4</strong>
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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 4, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs119463992 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463992;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/rs119463992?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=rs119463992" 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=rs119463992" 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=RCV000003362 OR RCV000724028 OR RCV001036532 OR RCV001192872 OR RCV001254647 OR RCV003466793 OR RCV004991964 OR RCV005041974" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003362, RCV000724028, RCV001036532, RCV001192872, RCV001254647, RCV003466793, RCV004991964, RCV005041974" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003362...</a>
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<p>In 2 sibs with FKTN-related limb-girdle muscular dystrophy (MDDGC4; <a href="/entry/611588">611588</a>) without mental retardation, <a href="#7" class="mim-tip-reference" title="Godfrey, C., Escolar, D., Brockington, M., Clement, E. M., Mein, R., Jimenez-Mallebrera, C., Torelli, S., Feng, L., Brown, S. C., Sewry, C. A., Rutherford, M., Shapira, Y., Abbs, S., Muntoni, F. <strong>Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.</strong> Ann. Neurol. 60: 603-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044012</a>] [<a href="https://doi.org/10.1002/ana.21006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17044012">Godfrey et al. (2006)</a> identified compound heterozygosity for a 920G-A transition in exon 8 of the FKTN gene, resulting in an arg307-to-gln (R307Q) substitution, and a 1-bp insertion (<a href="#0005">607440.0005</a>). Functional expression studies showed that the R307Q mutant protein was expressed and localized correctly within the cell. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17044012" 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="#13" 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 compound heterozygosity for 2 mutations in the FKTN gene (R307Q and 42delG; <a href="#0019">607440.0019</a>) in 1 of 81 Italian patients with congenital muscular dystrophy (MDDGB4; <a href="/entry/613152">613152</a>) associated with defective glycosylation of alpha-dystroglycan. The patient did not have mental retardation and had no structural brain abnormalities. <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><p><a href="#23" class="mim-tip-reference" title="Vuillaumier-Barrot, S., Quijano-Roy, S., Bouchet-Seraphin, C., Maugenre, S., Peudenier, S., Van den Bergh, P., Marcorelles, P., Avila-Smirnow, D., Chelbi, M., Romero, N. B., Carlier, R. Y., Estournet, B., Guicheney, P., Seta, N. <strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong> Neuromusc. Disord. 19: 182-188, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179078</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.12.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179078">Vuillaumier-Barrot et al. (2009)</a> identified a homozygous R307Q mutation in a Turkish girl with a moderately severe form of muscular dystrophy. She had delayed motor development, pes equinovarus, increased serum creatine kinase, generalized proximal muscle weakness, and diffuse muscle wasting of the calves. The disorder was progressive, and she lost ambulation at 11 years and developed contractures. Intelligence and brain MRI were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179078" 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 CARDIOMYOPATHY, DILATED, 1X</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">rs119463993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463993;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=rs119463993" 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=rs119463993" 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=RCV000003364" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003364" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003364</a>
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<p>In a 30-year-old Japanese man and his 33-year-old sister with dilated cardiomyopathy (CMD1X; <a href="/entry/611615">611615</a>), <a href="#14" class="mim-tip-reference" title="Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y., Ogino, M., Takada, F., Eriguchi, M., Kotooka, N., Campbell, K. P., Osawa, M., Nishino, I. <strong>Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.</strong> Ann. Neurol. 60: 597-602, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17036286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17036286</a>] [<a href="https://doi.org/10.1002/ana.20973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17036286">Murakami et al. (2006)</a> identified compound heterozygosity for 2 mutations in the FKTN gene: the 3-kb retroposon insertion (<a href="#0001">607440.0001</a>) and a 1073A-C transversion, resulting in a gln358-to-pro (Q358P) substitution at a highly conserved residue. The brother was diagnosed with idiopathic dilated cardiomyopathy and congestive heart failure at 17 years of age and underwent cardiac transplantation at age 18; he began having slowly progressive proximal muscle weakness of the lower extremities at 24 years of age, and by age 30, he had calf hypertrophy, Gowers sign, and mild waddling gait. His sister was noted to have cardiomegaly on chest x-ray at age 20, but had no symptoms until 27 years of age, when she developed rapidly progressive heart failure during pregnancy; after induced abortion, her cardiac function recovered and she remained asymptomatic. The unaffected parents were each heterozygous for 1 of the mutations, respectively, and the missense mutation was not found in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17036286" 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 CARDIOMYOPATHY, DILATED, 1X</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> rs119463994 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463994;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/rs119463994?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=rs119463994" 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=rs119463994" 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=RCV000003365 OR RCV000441410 OR RCV002512702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003365, RCV000441410, RCV002512702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003365...</a>
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<p>In a Japanese brother and sister and 2 unrelated Japanese women with dilated cardiomyopathy (CMD1X; <a href="/entry/611615">611615</a>), <a href="#14" class="mim-tip-reference" title="Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y., Ogino, M., Takada, F., Eriguchi, M., Kotooka, N., Campbell, K. P., Osawa, M., Nishino, I. <strong>Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.</strong> Ann. Neurol. 60: 597-602, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17036286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17036286</a>] [<a href="https://doi.org/10.1002/ana.20973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17036286">Murakami et al. (2006)</a> identified compound heterozygosity for 2 mutations in the FKTN gene: the 3-kb retroposon insertion (<a href="#0001">607440.0001</a>) and a 536G-C transversion resulting in an arg179-to-thr (R179T) substitution at a highly conserved residue. The brother was a swimmer with no muscle weakness or calf hypertrophy. He developed dyspnea at 12 years of age, was diagnosed with cardiomyopathy, and died within a month from heart failure; autopsy revealed severe CMD with lymphocytic infiltration and fibrosis. His 22-year-old sister was diagnosed with cardiomyopathy at 11 years of age and was noted to have calf hypertrophy, but remained asymptomatic with no muscle weakness. The 2 unrelated Japanese women were diagnosed with CMD at ages 46 and 30 years, respectively; the former had mild proximal muscle weakness without facial muscle involvement, and the latter was noted to have proximal muscle weakness with a waddling gait. The unaffected parents of the brother and sister were each heterozygous for 1 of the mutations, respectively, and the missense mutation was not found in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17036286" 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 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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FKTN, GLY125SER
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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> rs34006675 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34006675;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/rs34006675?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=rs34006675" 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=rs34006675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>This variant, formerly titled WALKER-WARBURG SYNDROME, FKTN-RELATED, has been reclassified based on the findings of <a href="#1" class="mim-tip-reference" title="Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F. <strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong> Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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/10.1126/scitranslmed.3001756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21228398">Bell et al. (2011)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21228398" 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 Spanish female infant diagnosed with Walker-Warburg syndrome (MDDGA4; <a href="/entry/253800">253800</a>), who died at day 5 of life, <a href="#4" class="mim-tip-reference" title="Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J. <strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong> Clin. Genet. 73: 139-145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18177472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18177472</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18177472">Cotarelo et al. (2008)</a> identified compound heterozygosity for a 373G-A transition in exon 5 of the FKTN gene, resulting in a gly125-to-ser (G125S) substitution, and a 473-bp deletion in exon 10 of the FKTN gene (<a href="#0013">607440.0013</a>) that includes the polyadenylation signal. The patient was not a carrier of the founder retrotransposal insertion (<a href="#0001">607440.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18177472" 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 preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, <a href="#1" class="mim-tip-reference" title="Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F. <strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong> Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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/10.1126/scitranslmed.3001756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21228398">Bell et al. (2011)</a> found that the G125S mutation in FKTN is a polymorphism carried by unaffected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21228398" 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 (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
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<p>For discussion of the 473-bp deletion in exon 10 of the FKTN gene, which included the polyadenylation signal, that was found in compound heterozygous state in a patient diagnosed with Walker-Warburg syndrome (MDDGA4; <a href="/entry/253800">253800</a>) by <a href="#4" class="mim-tip-reference" title="Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J. <strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong> Clin. Genet. 73: 139-145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18177472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18177472</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18177472">Cotarelo et al. (2008)</a>, see <a href="#0012">607440.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18177472" 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, 4</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">rs119463995 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463995;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=rs119463995" 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=rs119463995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 brothers of Japanese and Caucasian ancestry with limb-girdle muscular dystrophy (MDDGC4; <a href="/entry/611588">611588</a>), <a href="#15" class="mim-tip-reference" title="Puckett, R. L., Moore, S. A., Winder, T. L., Willer, T., Romansky, S. G., Covault, K. K., Campbell, K. P., Abdenur, J. E. <strong>Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.</strong> Neuromusc. Disord. 19: 352-356, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342235[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.nmd.2009.03.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19342235">Puckett et al. (2009)</a> identified compound heterozygosity for 2 mutations in the FKTN gene: a 340G-A transition in exon 4, resulting in an ala114-to-thr (A114T) substitution, and a 527T-C transition in exon 5, resulting in a phe176-to-ser (F176S; <a href="#0015">607440.0015</a>) substitution. The A114T mutation was previously found in 2 sibs with a similar presentation (<a href="#6" class="mim-tip-reference" title="Godfrey, C., Clement, E., Mein, R., Brockington, M., Smith, J., Talim, B., Straub, V., Robb, S., Quinlivan, R., Feng, L., Jimenez-Mallebrera, C., Mercuri, E., and 10 others. <strong>Refining genotype-phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.</strong> Brain 130: 2725-2735, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878207</a>] [<a href="https://doi.org/10.1093/brain/awm212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878207">Godfrey et al., 2007</a>). The F176S mutation, which occurs in a highly conserved residue, was not found in 90 control individuals. The A114T mutation was inherited from the Caucasian father, and the F176S mutation was inherited from the Japanese mother; both parents were unaffected. The phenotype was relatively mild, and there was no cardiac or cognitive involvement. Skeletal muscle biopsy showed defective glycosylation of alpha-dystroglycan. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17878207+19342235" 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, 4</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">rs119463996 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119463996;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=rs119463996" 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=rs119463996" 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 527T-C transition in exon 5 of the FKTN gene, resulting in a phe176-to-ser (F176S; 607440.0015) substitution, that was found in compound heterozygous state in 2 brothers of Japanese and Caucasian ancestry with limb-girdle muscular dystrophy (MDDGC4; 611588) by <a href="#15" class="mim-tip-reference" title="Puckett, R. L., Moore, S. A., Winder, T. L., Willer, T., Romansky, S. G., Covault, K. K., Campbell, K. P., Abdenur, J. E. <strong>Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.</strong> Neuromusc. Disord. 19: 352-356, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342235[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.nmd.2009.03.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19342235">Puckett et al. (2009)</a>, see <a href="#0014">607440.0014</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19342235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs119464997 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119464997;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/rs119464997?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=rs119464997" 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=rs119464997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 Portuguese sisters with Fukuyama congenital muscular dystrophy (MDDGA4; <a href="/entry/253800">253800</a>), <a href="#23" class="mim-tip-reference" title="Vuillaumier-Barrot, S., Quijano-Roy, S., Bouchet-Seraphin, C., Maugenre, S., Peudenier, S., Van den Bergh, P., Marcorelles, P., Avila-Smirnow, D., Chelbi, M., Romero, N. B., Carlier, R. Y., Estournet, B., Guicheney, P., Seta, N. <strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong> Neuromusc. Disord. 19: 182-188, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179078</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.12.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179078">Vuillaumier-Barrot et al. (2009)</a> identified compound heterozygosity for 2 mutations in the FKTN gene: 509C-A transversion in exon 5 of the FKTN gene, resulting in an ala170-to-gly (A170E) substitution, and a 1112A-G transition in exon 9, resulting in a tyr371-to-cys (Y371C; <a href="#0017">607440.0017</a>) substitution. Both girls had a severe phenotype, with congenital muscular dystrophy, joint contracture, respiratory insufficiency, and mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179078" 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 human mutant FKTN constructs with expression in mouse myoblasts, <a href="#19" class="mim-tip-reference" title="Tachikawa, M., Kanagawa, M., Yu, C.-C., Kobayashi, K., Toda, T. <strong>Mislocalization of fukutin protein by disease-causing missense mutations can be rescued with treatments directed at folding amelioration.</strong> J. Biol. Chem. 287: 8398-8406, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22275357[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/10.1074/jbc.M111.300905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275357">Tachikawa et al. (2012)</a> found that the A170E and Y371C mutant proteins showed aberrant accumulation in the endoplasmic reticulum due to protein misfolding and failure of the anterograde pathway, in contrast to wildtype FKTN which localized to the Golgi apparatus. Expression studies in Fktn-null mouse embryonic cells showed that the mutant proteins retained normal glycosylation activity, indicating that these disease-causing mutations are pathogenic due to abnormal folding and localization. Low-temperature culture or treatment with curcumin variably corrected the subcellular localization of the missense mutant proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275357" 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>.0017 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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> rs119464998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119464998;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/rs119464998?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=rs119464998" 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=rs119464998" 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 1112A-G transition in exon 9 of the FKTN gene, resulting in a tyr371-to-cys (Y371C) substitution, that was found in compound heterozygous state in 2 Portuguese sisters with Fukuyama congenital muscular dystrophy (MDDGA4; <a href="/entry/253800">253800</a>) by <a href="#23" class="mim-tip-reference" title="Vuillaumier-Barrot, S., Quijano-Roy, S., Bouchet-Seraphin, C., Maugenre, S., Peudenier, S., Van den Bergh, P., Marcorelles, P., Avila-Smirnow, D., Chelbi, M., Romero, N. B., Carlier, R. Y., Estournet, B., Guicheney, P., Seta, N. <strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong> Neuromusc. Disord. 19: 182-188, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179078</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.12.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179078">Vuillaumier-Barrot et al. (2009)</a>, see <a href="#0016">607440.0016</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179078" 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 WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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> rs267606814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606814;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/rs267606814?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=rs267606814" 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=rs267606814" 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=RCV000003371 OR RCV000498134 OR RCV000795218 OR RCV002444418 OR RCV003466795 OR RCV004819203 OR RCV005003319" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003371, RCV000498134, RCV000795218, RCV002444418, RCV003466795, RCV004819203, RCV005003319" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003371...</a>
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<p>In a patient with Walker-Warburg syndrome (MDDGA4; <a href="/entry/253800">253800</a>), <a href="#6" class="mim-tip-reference" title="Godfrey, C., Clement, E., Mein, R., Brockington, M., Smith, J., Talim, B., Straub, V., Robb, S., Quinlivan, R., Feng, L., Jimenez-Mallebrera, C., Mercuri, E., and 10 others. <strong>Refining genotype-phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.</strong> Brain 130: 2725-2735, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878207</a>] [<a href="https://doi.org/10.1093/brain/awm212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878207">Godfrey et al. (2007)</a> identified a homozygous 919C-T transition in exon 8 of the FKTN gene, resulting in an arg307-to-ter (R307X) substitution. The patient was 1 of 92 patients with a dystroglycanopathy. Although clinical details were limited, the patient had neonatal onset, contractures, muscle hypertrophy, and increased serum creatine kinase. Eye abnormalities included retinal detachment and microphthalmia. Brain MRI showed cerebellar hypoplasia, white matter abnormalities, hydrocephalus, and brainstem involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17878207" 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 WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 4</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">rs1309132512 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1309132512;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=rs1309132512" 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=rs1309132512" 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=RCV000671524 OR RCV000800445 OR RCV002282313" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000671524, RCV000800445, RCV002282313" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000671524...</a>
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<p>For discussion of the 1-bp deletion (42delG) in the FKTN gene that was found in compound heterozygous state in a patient with congenital muscular dystrophy-dystroglycanopathy (MDDGB4; 613152) by <a href="#13" 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>, see <a href="#0009">607440.0009</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'})"><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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Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
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<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
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Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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=21228398" 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/10.1126/scitranslmed.3001756" target="_blank">Full Text</a>]
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Beltran-Valero de Bernabe, D., van Bokhoven, H., van Beusekom, E., Van den Akker, W., Kant, S., Dobyns, W. B., Cormand, B., Currier, S., Hamel, B., Talim, B., Topaloglu, H., Brunner, H. G.
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<strong>A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype.</strong>
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J. Med. Genet. 40: 845-848, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14627679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14627679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14627679" 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.40.11.845" target="_blank">Full Text</a>]
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Colombo, R., Bignamini, A. A., Carobene, A., Sasaki, J., Tachikawa, M., Kobayashi, K., Toda, T.
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<strong>Age and origin of the FCMD 3-prime-untranslated-region retrotransposal insertion mutation causing Fukuyama-type congenital muscular dystrophy in the Japanese population.</strong>
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Hum. Genet. 107: 559-567, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153909" 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/s004390000421" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2007.00936.x" target="_blank">Full Text</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 href="https://doi.org/10.1093/brain/awm212" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.21006" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.57.1.115" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddn387" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20669" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/28653" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/8.12.2303" target="_blank">Full Text</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 href="https://doi.org/10.1016/j.nmd.2009.03.001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(sici)1096-8628(20000529)92:3<184::aid-ajmg5>3.0.co;2-n" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/9.20.3083" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.10491" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22275357[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=22275357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1074/jbc.M111.300905" 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="20" class="mim-anchor"></a>
|
|
<a id="Takeda2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeda, S., Kondo, M., Sasaki, J., Kurahashi, H., Kano, H., Arai, K., Misaki, K., Fukui, T., Kobayashi, K., Tachikawa, M., Imamura, M., Nakamura, Y., Shimizu, T., Murakami, T., Sunada, Y., Fujikado, T., Matsumura, K., Terashima, T., Toda, T.
|
|
<strong>Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development.</strong>
|
|
Hum. Molec. Genet. 12: 1449-1459, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12783852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12783852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12783852" 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/ddg153" 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="21" class="mim-anchor"></a>
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<a id="Taniguchi-Ikeda2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Taniguchi-Ikeda, M., Kobayashi, K., Kanagawa, M., Yu, C., Mori, K., Oda, T., Kuga, A., Kurahashi, H., Akman, H. O., DiMauro, S., Kaji, R., Yokota, T., Takeda, S., Toda, T.
|
|
<strong>Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.</strong>
|
|
Nature 478: 127-131, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21979053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21979053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21979053[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=21979053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/nature10456" 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="22" class="mim-anchor"></a>
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<a id="Toda1996" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Toda, T., Miyake, M., Kobayashi, K., Mizuno, K., Saito, K., Osawa, M., Nakamura, Y., Kanazawa, I., Nakagome, Y., Yokunaga, K., Nakahori, Y.
|
|
<strong>Linkage-disequilibrium mapping narrows the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region to less than 100 kb.</strong>
|
|
Am. J. Hum. Genet. 59: 1313-1320, 1996.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Vuillaumier-Barrot2009" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
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Vuillaumier-Barrot, S., Quijano-Roy, S., Bouchet-Seraphin, C., Maugenre, S., Peudenier, S., Van den Bergh, P., Marcorelles, P., Avila-Smirnow, D., Chelbi, M., Romero, N. B., Carlier, R. Y., Estournet, B., Guicheney, P., Seta, N.
|
|
<strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong>
|
|
Neuromusc. Disord. 19: 182-188, 2009.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179078" 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.2008.12.005" 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="Watanabe2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watanabe, M., Kobayashi, K., Jin, F., Park, K. S., Yamada, T., Tokunaga, K., Toda, T.
|
|
<strong>Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations.</strong>
|
|
Am. J. Med. Genet. 138A: 344-348, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16222679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16222679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16222679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30978" 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="Xiong2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Xiong, H., Wang, S., Kobayashi, K., Jiang, Y., Wang, J., Chang, X., Yuan, Y., Liu, J., Toda, T., Fukuyama, Y., Wu, X.
|
|
<strong>Fukutin gene retrotransposal insertion in a non-Japanese Fukuyama congenital muscular dystrophy (FCMD) patient.</strong>
|
|
Am. J. Med. Genet. 149A: 2403-2408, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19842201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19842201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19842201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33057" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/13/2012
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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">
|
|
Ada Hamosh - updated : 1/10/2012<br>Cassandra L. Kniffin - updated : 2/10/2011<br>Cassandra L. Kniffin - updated : 12/4/2009<br>Cassandra L. Kniffin - updated : 10/27/2009<br>George E. Tiller - updated : 8/10/2009<br>Marla J. F. O'Neill - updated : 7/10/2008<br>Marla J. F. O'Neill - updated : 11/26/2007<br>Cassandra L. Kniffin - updated : 11/7/2007<br>Victor A. McKusick - updated : 2/8/2007<br>Cassandra L. Kniffin - updated : 3/9/2006<br>George E. Tiller - updated : 3/21/2005<br>Victor A. McKusick - updated : 5/26/2004<br>Cassandra L. Kniffin - updated : 1/6/2004<br>Cassandra L. Kniffin - updated : 5/7/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 12/23/2002
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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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<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 : 10/09/2019<br>carol : 06/06/2019<br>carol : 11/19/2018<br>carol : 11/16/2018<br>carol : 09/26/2018<br>carol : 10/02/2015<br>carol : 10/20/2014<br>mcolton : 10/15/2014<br>carol : 10/3/2014<br>carol : 8/1/2013<br>ckniffin : 7/31/2013<br>alopez : 6/19/2012<br>ckniffin : 6/13/2012<br>alopez : 5/18/2012<br>alopez : 1/10/2012<br>terry : 1/10/2012<br>alopez : 9/15/2011<br>wwang : 4/14/2011<br>ckniffin : 2/10/2011<br>carol : 11/12/2010<br>carol : 11/10/2010<br>ckniffin : 11/8/2010<br>ckniffin : 12/4/2009<br>wwang : 11/13/2009<br>ckniffin : 10/27/2009<br>wwang : 8/20/2009<br>terry : 8/10/2009<br>wwang : 7/11/2008<br>terry : 7/10/2008<br>ckniffin : 11/26/2007<br>carol : 11/26/2007<br>wwang : 11/26/2007<br>ckniffin : 11/7/2007<br>alopez : 2/13/2007<br>terry : 2/8/2007<br>wwang : 3/17/2006<br>wwang : 3/17/2006<br>wwang : 3/16/2006<br>ckniffin : 3/9/2006<br>alopez : 3/21/2005<br>tkritzer : 9/20/2004<br>tkritzer : 9/13/2004<br>tkritzer : 6/7/2004<br>terry : 5/26/2004<br>tkritzer : 1/13/2004<br>ckniffin : 1/6/2004<br>tkritzer : 6/9/2003<br>ckniffin : 5/7/2003<br>ckniffin : 12/27/2002<br>carol : 12/27/2002<br>ckniffin : 12/27/2002<br>ckniffin : 12/26/2002
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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">
|
|
<strong>*</strong> 607440
|
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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">
|
|
|
|
FUKUTIN; FKTN
|
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|
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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>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FCMD GENE; FCMD
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: FKTN</em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
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<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 111502003, 726618007;
|
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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">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 9q31.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 9:105,558,130-105,641,118 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
9q31.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1X
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
611615
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
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</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
253800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613152
|
|
</span>
|
|
</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, 4
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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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611588
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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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</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>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The FKTN gene encodes a type II transmembrane protein that is targeted to the Golgi apparatus through an N-terminal signal anchor (Esapa et al., 2002). </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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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>On the basis of haplotype analysis, Toda et al. (1996) concluded that the locus for Fukuyama congenital muscular dystrophy (FCMD; 253800) lies within a 100-kb region on chromosome 9q13. By positional cloning, Kobayashi et al. (1998) identified the FKTN gene. The deduced 461-amino acid protein, which they termed fukutin, was expressed in various tissues in normal individuals. The predicted protein contains an N-terminal signal sequence which, together with results from transfection experiments, suggested that fukutin is a secreted protein. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By positional cloning, Kobayashi et al. (1998) identified the FKTN gene on chromosome 9q31. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</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>In transfected COS-7 cells, Kobayashi et al. (1998) found evidence of colocalization of fukutin with a Golgi marker and a granular cytoplasmic distribution, suggesting that fukutin passes through the Golgi before being packaged into secretory vesicles. The signal was not seen at the plasma membrane, however, where most proteins responsible for muscular dystrophies are located. Kobayashi et al. (1998) suggested that fukutin may be located in the extracellular matrix, where it interacts with and reinforces a large complex encompassing the outside and inside of muscle membranes; alternatively, as a secreted protein, fukutin may cause muscular dystrophy by an unknown mechanism. </p><p>Using Northern blot and RT-PCR analysis, Sasaki et al. (2000) determined that the fukutin gene is expressed at similar levels in control fetal and adult brain, but is much reduced in FCMD brains. Tissue in situ hybridization analysis revealed fukutin mRNA expression in migrating neurons, including Cajar-Retzius cells and adult cortical neurons, as well as hippocampal pyramidal cells and cerebellar Purkinje cells. However, no expression was observed in the glia limitans, the subpial astrocytes (which contribute to basement membrane formation), or other glial cells. In the FCMD brain, neurons in regions with no dysplasia showed fair expression, whereas transcripts were nearly undetectable in the overmigrated dysplastic region. The authors hypothesized that fukutin may influence neuronal migration itself rather than formation of the basement membrane. </p><p>Alpha-dystroglycan (DAG1; 128239) is a cell surface protein that plays an important role in the assembly of the extracellular matrix in muscle, brain, and peripheral nerves by linking the basal lamina to cytoskeletal proteins. Using PCR, immunohistochemistry, and immunoblotting to analyze samples from patients with FCMD, Hayashi et al. (2001) confirmed a deficiency of fukutin and found marked deficiency of highly glycosylated DAG1 in skeletal and cardiac muscle and reduced amounts of DAG1 in brain tissue. Beta-dystroglycan (see 128239) was normal in all tissues examined. These findings supported the suggestion that fukutin deficiency affects the modification of glycosylation of DAG1, which then cannot localize or function properly and may be degraded or eluted from the extracellular surface membrane of the muscle fiber. Hayashi et al. (2001) concluded that this disruption underlies the developmental, structural, and functional damage to muscles in patients with FCMD. </p><p>Using transfection experiments, Esapa et al. (2002) determined that fukutin and fukutin-related protein (FKRP; 606596) are Golgi-resident proteins and that they are targeted to the medial Golgi apparatus through their N termini and transmembrane domains. </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><strong><em>Muscular Dystrophy-Dystroglycanopathy, Types A4, B4, and C4</em></strong></p><p>
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Mutation in the FKTN gene can cause 3 different forms of muscular dystrophy-dystroglycanopathy (MDDG): a severe congenital form with brain and eye anomalies (type A4; MDDGA4, 253800), formerly designated Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), or muscle-eye-brain disease (MEB); a less severe congenital form without impaired intellectual development (type B4; MDDGB4; 613152); and a milder limb-girdle form (type C4; MDDGC4; 611588), also designated LGMDR13 and LGMD2M.</p><p>In Japan, Toda et al. (1996) and Kobayashi et al. (1998) described a haplotype that is shared by more than 80% of chromosomes of patients with Fukuyama congenital muscular dystrophy (FCMD; MDDGA4), indicating that most chromosomes bearing the mutation could be derived from a single ancestor. Kobayashi et al. (1998) reported that there is a retrotransposal insertion (607440.0001) of tandemly repeated sequences within the candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence was about 3 kb long and was located in the 3-prime untranslated region (UTR) of the gene. One component of the 3,062-bp insert was a SINE (short interspersed sequence)-type retroposon sequence. Kobayashi et al. (1998) stated that FCMD is the first human disease known to be caused by an ancient retrotransposal integration. In patients with FCMD, Kobayashi et al. (1998) identified 2 independent mutations (607440.0002 and 607440.0003) in the FKTN gene. Watanabe et al. (2005) noted that the insertion was of a class of retroposon referred to as SINE-VNTR-Alu (SVA). </p><p>Kondo-Iida et al. (1999) extended the known mutation repertoire of the FKTN gene. In a systematic analysis of the FKTN gene in 107 unrelated patients with FCMD, they found 4 novel nonfounder mutations in 5 patients: 1 missense, 1 nonsense, 1 L1 insertion (607440.0004), and one 1-bp insertion (607440.0005). </p><p>In patients with a clinical diagnosis of Walker-Warburg syndrome (MDDGA4), Beltran-Valero de Bernabe et al. (2003) and Silan et al. (2003) independently identified mutations in the FKTN gene (607440.0006 and 607440.0007, respectively). </p><p>In cell lines from unrelated Ashkenazi Jewish parents and their son, who was diagnosed with WWS, Cotarelo et al. (2008) identified the 1-bp insertion in the FKTN gene (607440.0005) that had previously been identified in compound heterozygosity in patients with FCMD and FKTN-related muscular dystrophy. The son was homozygous for the insertion, and the unaffected parents were heterozygous carriers. In a Spanish female infant diagnosed with WWS who died at day 5 of life, Cotarelo et al. (2008) identified compound heterozygosity for a missense mutation (G125S; 607440.0012) and a 473-bp deletion (607440.0013) in the FKTN gene. </p><p>In 3 patients with limb-girdle muscular dystrophy due to defective glycosylation of dystroglycan (MDDGC4; 611588), Godfrey et al. (2006) identified compound heterozygosity for mutations in the FKTN gene (607440.0005; 607440.0008; 607440.0009). The authors noted that the phenotype was much less severe than that observed in the allelic disorder Fukuyama congenital muscular dystrophy. The patients showed early-onset proximal muscular dystrophy, normal intelligence and brain structure, and favorable response to steroid treatment. </p><p>Puckett et al. (2009) identified compound heterozygous mutations in the FKTN gene (A114T, 607440.0014 and F176S, 607440.0015) in 2 brothers of Japanese and Caucasian ancestry with FKTN-related limb-girdle muscular dystrophy (MDDGC4). The phenotype was relatively mild, and there was no cardiac or cognitive involvement. Skeletal muscle biopsy showed defective glycosylation of alpha-dystroglycan. </p><p>Godfrey et al. (2007) identified FKTN mutations in 6 of 92 patients with evidence of a muscular dystrophy due to defective glycosylation of alpha-dystroglycan. Only 2 had structural brain anomalies: 1 with WWS and 1 with MEB. </p><p>Mercuri et al. (2009) identified compound heterozygosity for 2 mutations in the FKTN gene (R307Q; 607440.0009 and 42delG; 607440.0019) in 1 of 81 Italian patients with congenital muscular dystrophy associated with defective glycosylation of alpha-dystroglycan (MDDGB4; 613152). The patient did not have mental retardation and had no structural brain abnormalities. </p><p>Taniguchi-Ikeda et al. (2011) demonstrated that aberrant mRNA splicing, induced by SINE-VNTR-Alu (SVA) exon trapping, underlies the molecular pathogenesis of FCMD (MDDGA4). Quantitative mRNA analysis pinpointed a region that was missing from transcripts in patients with FCMD. This region spans part of the 3-prime end of the fukutin coding region, a proximal part of the 3-prime UTR, and the SVA insertion. Correspondingly, fukutin mRNA transcripts in patients with FCMD and SVA knockin model mice were shorter than the expected length. Sequence analysis revealed an abnormal splicing event, provoked by a strong acceptor site in SVA and a rare alternative donor site in fukutin exon 10. The resulting product truncates the fukutin carboxy terminus and adds 129 amino acids encoded by the SVA. Introduction of antisense oligonucleotides targeting the splice acceptor, the predicted exonic splicing enhancer, and the intronic splicing enhancer prevented pathogenic exon trapping by SVA in cells of patients with FCMD and model mice, rescuing normal fukutin mRNA expression and protein production. Antisense oligonucleotide treatment also restored fukutin functions, including O-glycosylation of alpha-dystroglycan (DAG1; 128239) and laminin (see 156225) binding by alpha-dystroglycan. Moreover, Taniguchi-Ikeda et al. (2011) observed exon trapping in other SVA insertions associated with disease (hypercholesterolemia, neutral lipid storage disease) and human-specific SVA insertion in a novel gene. Thus, Taniguchi-Ikeda et al. (2011) concluded that, although splicing into SVA is known, they had discovered in human disease a role for SVA-mediated exon trapping, and demonstrated the promise of splicing modulation therapy as the first radical clinical treatment for FCMD and other SVA-mediated diseases. </p><p>Using human mutant FKTN constructs with expression in mouse myoblasts, Tachikawa et al. (2012) found that 4 pathogenic missense mutations (A170E, 607440.0016; H172R; H186R; and Y371C, 607440.0017) showed aberrant accumulation in the endoplasmic reticulum (ER) due to protein misfolding and failure of the anterograde pathway, in contrast to wildtype FKTN, which localized to the Golgi apparatus. The POMGNT1 (606822) protein also mislocalized to the ER when coexpressed with mutant FKTN. Low-temperature culture or treatment with curcumin variably corrected the subcellular localization of the missense mutant proteins. Expression studies in Fktn-null mouse embryonic cells showed that the mutant proteins retained normal glycosylation activity, indicating that some disease-causing mutations are pathogenic due to abnormal folding and localization. The findings suggested a therapeutic strategy for certain FKTN mutations. </p><p><strong><em>Dilated Cardiomyopathy 1X</em></strong></p><p>
|
|
Murakami et al. (2006) analyzed the FKTN gene in 6 Japanese patients with CMD and mild or no limb-girdle muscle involvement (CMD1X; 611615) and identified compound heterozygosity in all for a 3-kb retrotransposal insertion (607440.0001) and another missense mutation (607440.0010 or 607440.0011, respectively). </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">
|
|
<strong>Genotype/Phenotype Correlations</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>Kondo-Iida et al. (1999) noted that the frequency of severe phenotypes, including Walker-Warburg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and a founder mutation on the other, than among probands who were homozygous for the 3-kb retrotransposon (607440.0001). Remarkably, they detected no FCMD patients with nonfounder (point) mutations on both alleles of the gene, suggesting that such cases might be embryonic lethal. This could explain why few FCMD cases are reported in non-Japanese populations. </p><p>In a Turkish patient with a severe phenotype that resembled Walker-Warburg syndrome, Silan et al. (2003) identified a homozygous nonfounder mutation in the FKTN gene (607440.0006). The patient died at 10 days of age. The authors noted that this was the first non-Japanese patient to be reported with a fukutin mutation, and that the mutation was the first reported nonfounder homozygous mutation. Beltran-Valero de Bernabe et al. (2003) reported a similar case (see 607440.0007). </p><p>To establish a genotype-phenotype correlation, Saito et al. (2000) performed haplotype analysis using microsatellite markers closest to the FKTN gene in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 probands with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder haplotype, whereas the other 2 were heterozygous for the haplotype. Of the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmologic abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype were heterozygous for the ancestral founder haplotype, and the other 1 homozygous for the haplotype. Saito et al. (2000) confirmed that at least 1 chromosome in each of the 56 FCMD patients had the ancestral founder haplotype. The rate of heterozygosity for this haplotype was significantly higher in severe cases than in typical or mild cases (P less than 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Takeda et al. (2003) reported that chimeric mice generated using embryonic stem cells targeted for both fukutin alleles developed severe muscular dystrophy, with the selective deficiency of alpha-dystroglycan (DAG1; 128239) and its laminin (see 156225)-binding activity. In addition, these mice showed laminar disorganization of the cortical structures in the brain with impaired laminin assembly, focal interhemispheric fusion, and hippocampal and cerebellar dysgenesis. Further, chimeric mice showed anomaly of the lens, loss of laminar structure in the retina, and retinal detachment. The authors concluded that fukutin is necessary for the maintenance of muscle integrity, cortical histiogenesis, and normal ocular development, and suggested a functional linkage between fukutin and alpha-dystroglycan. </p><p>Kanagawa et al. (2009) generated a mouse model of FCMD by introducing the disease-causing retrotransposon into the mouse Fktn gene. Knockin mice exhibited hypoglycosylated alpha-dystroglycan; however, no signs of muscular dystrophy were observed. More sensitive methods detected minor levels of intact alpha-dystroglycan, and solid-phase assays determined laminin-binding levels to be 50% of normal. In contrast, intact alpha-dystroglycan was undetectable in the dystrophic Large(myd) mouse (see 603590), and laminin-binding activity was markedly reduced. This suggested that a small amount of intact alpha-dystroglycan may be sufficient to maintain muscle cell integrity in knockin mice. Transfer of fukutin into knockin mice restored glycosylation of alpha-dystroglycan. Transfer of LARGE produced laminin-binding forms of alpha-dystroglycan in both knockin mice and the Pomgnt1 (606822)-mutant mouse, which is another model of dystroglycanopathy. Kanagawa et al. (2009) suggested that even partial restoration of alpha-dystroglycan glycosylation and laminin-binding activity by replacing or augmenting glycosylation-related genes may effectively deter dystroglycanopathy progression and thus provide therapeutic benefits. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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CARDIOMYOPATHY, DILATED, 1X, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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FKTN, 3-KB INS, SVA RETROTRANSPOSON INS
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<br />
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ClinVar: RCV000003351, RCV000003352
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A, 4</em></strong></p><p>
|
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Kobayashi et al. (1998) found that 87% of mutant alleles causing the autosomal recessive disorder Fukuyama congenital muscular dystrophy (MDDGA4; 253800) carried an insertion of a 3,062-bp transposon, situated in the 3-prime UTR of the FKTN gene. </p><p>Most Japanese patients with the retrotransposal insertion in the FKTN gene share a common founder haplotype. By applying 2 methods for the study of linkage disequilibrium between flanking polymorphic markers and the disease locus, and of its decay over time, Colombo et al. (2000) calculated the age of the insertion mutation to be approximately 102 generations (95% CI: 86-117 g), or slightly less. The estimated age dates the most recent common ancestor of the mutation-bearing chromosomes back to the time (or a few centuries before) the Yayoi people began migrating to Japan from the Korean peninsula. FCMD was the first human disease known to be caused primarily by an ancient retrotransposal integration. </p><p>Kato et al. (2004) stated that 9 nonfounder mutations had been identified in Japanese FCMD patients. Severe phenotype was significantly more frequent in patients who were compound heterozygotes for a point mutation and the 3-kb founder insertion in the FKTN gene than in homozygotes for the founder mutation. The authors described a PCR-based diagnostic method for rapid detection of the insertion mutation. Using this method, they screened 18 FCMD patients and found 16 homozygotes and 2 heterozygotes for the insertion. In the general Japanese population, they found that 6 of 676 persons were heterozygous carriers. Furthermore, they found 3 homozygotes for the FCMD founder mutation among 97 patients who had been said to have probable Duchenne muscular dystrophy (310200) or Becker muscular dystrophy (300376) (DMD/BMD) without any mutation in the DMD gene (300377). On the other hand, there were no FCMD homozygotes but 4 heterozygous carriers among 335 patients with DMD mutations. </p><p>By sequence analysis, Watanabe et al. (2005) characterized the insertion mutation and found that it was enclosed by target-site duplications at both ends. They noted that the sequence motif was characteristic of a class of retroposon referred to as SINE-VNTR-Alu (SVA). </p><p>Watanabe et al. (2005) established a rapid PCR-based diagnostic method using 3 primers simultaneously in order to detect the 3,062-bp retrotransposal insertion. Fifteen founder chromosomes were detected among 2,814 Japanese individuals. Heterozygous carriers were identified in various regions throughout Japan, with a carrier frequency of approximately 1 in 188. The insertion mutation was found in 1 in 935 Korean individuals but not among 203 Mongolians and 766 mainland Chinese, suggesting that FCMD carriers are rare outside of Japan. </p><p>Xiong et al. (2009) reported a Chinese boy with FCMD who was compound heterozygous for 2 mutations in the fukutin gene: the common 3-kb retroposon insertion and R47X (607440.0002). Although the boy's parents were born in Henan and Shanxi Provinces and had no known Japanese ancestry, haplotype analysis showed that both mutant alleles were on Japanese-derived haplotypes. </p><p><strong><em>Cardiomyopathy, Dilated, 1X</em></strong></p><p>
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In 6 Japanese patients from 4 families with dilated cardiomyopathy and mild or no limb-girdle involvement (CMD1X; 611615), Murakami et al. (2006) identified compound heterozygosity in all for the 3-kb retroposon insertion and another missense mutation: Q358P (607440.0010) or R179T (607440.0011), respectively. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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FKTN, ARG47TER
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<br />
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SNP: rs119463990,
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gnomAD: rs119463990,
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ClinVar: RCV000003353, RCV000594458, RCV000811518, RCV003372594, RCV003472962
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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>Kobayashi et al. (1998) searched for inactivating mutations in the FKTN gene in patients with Fukuyama congenital muscular dystrophy (MDDGA4; 253800) lacking the haplotype indicative of the 3-kb insertion (607440.0001) on 1 chromosome. In a total of 6 families, the noninsertion-bearing chromosome showed a nonsense mutation in the FKTN gene: a C-to-T transition at base 250, resulting in premature termination (CGA to TGA; arg47 to ter). </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 WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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FKTN, 2-BP DEL, NT298
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<br />
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SNP: rs587777813,
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ClinVar: RCV000003354, RCV002512701
|
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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>Kobayashi et al. (1998) found that a girl with Fukuyama congenital muscular dystrophy (MDDGA4; 253800) had inherited the common retrotransposal insertion mutation (607440.0001) from her Japanese mother and a 2-bp deletion at bases 298-299 (codon 63), causing a frameshift and a premature stop at codon 75, from her American father (of English and German extraction). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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FKTN, L1 INS
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<br />
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ClinVar: RCV000003355
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated patients with unusually severe FCMD (MDDGA4; 253800), Kondo-Iida et al. (1999) detected a 1.2-kb L1 insertion in the FKTN gene. Each patient carried the founder 3-kb retrotransposal insertion (607440.0001) on one allele and a distinctive haplotype on the other. Sequence analysis revealed that the 3-prime region of an L1 repetitive element had been inserted 24 basepairs before the intron 7-exon 8 boundary. The patients' RNA was tested for the effects of the insertion by means of reverse transcriptase-PCR analysis, using primers that amplified exons 5-10. Products of various sizes were obtained, suggesting exon skipping. </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>.0005 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4, INCLUDED
|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
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|
FKTN, 1-BP INS, 1279A
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|
<br />
|
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|
SNP: rs398123555,
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|
ClinVar: RCV000003356, RCV000003357, RCV000079427, RCV000634081, RCV000778871, RCV002326661, RCV003466792, RCV005003318
|
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|
|
|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a girl with severe FCMD (MDDGA4; 253800) including microphthalmia, Kondo-Iida et al. (1999) identified a 1-bp insertion (1279insA) in exon 9 of the FKTN gene, causing a frameshift and a premature stop at codon 403. The patient carried the founder insertion (607440.0001) from her mother; however, the 1-bp insertion could not be detected in the father by either SSCP or by direct sequencing, leading Kondo-Iida et al. (1999) to conclude that this was the first example of a de novo mutation. </p><p>In a cell line from an Ashkenazi Jewish male diagnosed with Walker-Warburg syndrome (MDDGA4), Cotarelo et al. (2008) identified homozygosity for a 1-bp insertion within a stretch of 6 adenine residues in exon 9 (1160_1168insA). Cell lines from the unrelated, unaffected parents revealed that they were heterozygous carriers of the insertion. </p><p>In 2 sibs and an unrelated child with FKTN-related limb-girdle muscular dystrophy (MDDGC4; 611588), Godfrey et al. (2006) identified compound heterozygosity for mutations in the FKTN gene. All 3 children had a 1-bp insertion in exon 9 (1167insA), which the authors stated was the same mutation as that identified by Kondo-Iida et al. (1999). The insertion was predicted to result in a frameshift at phe390 and premature termination, followed by nonsense-mediated decay of the mRNA transcript. The second mutant allele identified was a 1-bp deletion (607440.0008) in 1 child and a missense mutation (R307Q; 607440.0009) in 2 sibs. The patients showed early-onset proximal muscular dystrophy, normal intelligence and brain structure, and favorable response to steroid treatment. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
FKTN, 1-BP INS, 504T
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<br />
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|
|
SNP: rs587777748,
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|
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ClinVar: RCV000003359, RCV001851611, RCV004566676
|
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|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish patient with a severe congenital muscular dystrophy phenotype most closely resembling Walker-Warburg syndrome (MDDGA4; 253800), Silan et al. (2003) identified a homozygous 1-bp insertion (504insT) in exon 5 of the FKTN gene. The first-cousin parents and an unaffected brother were heterozygous for the mutation. The patient presented at birth with hypotonia, hydrocephalus, respiratory difficulties, ocular abnormalities, and elevated muscle enzymes, and died on the tenth day of life. Postmortem examination revealed severe malformations of the central nervous system, including agyria and cortical disorganization, and congenital muscular dystrophy. Silan et al. (2003) noted that this was the first reported case of a fukutin mutation found outside the Japanese population and the first reported case of a homozygous nonfounder mutation, which was believed to be embryonic lethal. Although the patient may be considered to have Fukuyama congenital muscular dystrophy because of the mutation in the FKTN gene, the authors noted that classification of the disease in this patient may be difficult because the phenotype is slightly different and resembles Walker-Warburg syndrome. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
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</div>
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|
|
</div>
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|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
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<div>
|
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<span class="mim-text-font">
|
|
|
|
FKTN, GLN116TER
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|
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|
<br />
|
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|
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SNP: rs119463991,
|
|
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|
|
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gnomAD: rs119463991,
|
|
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|
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ClinVar: RCV000003360, RCV001067436, RCV003472963
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish patient diagnosed with Walker-Warburg syndrome (MDDGA4; 253800), Beltran-Valero de Bernabe et al. (2003) identified a homozygous gln116-to-ter (Q116X) mutation in the FKTN gene. Born to second-degree consanguineous parents, the patient had macrocephaly, abnormal eyes, severe hypotonia, and severe brain malformations, including hydrocephalus, agyria/pachygyria, absent corpus callosum and cerebellar vermis, and white matter hyperlucencies. The authors noted that the phenotype in this patient was more consistent with Walker-Warburg syndrome than with Fukuyama congenital muscular dystrophy, and established a genotype/phenotype correlation for fukutin mutations that cause complete loss of protein function. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, 1-BP DEL, 1363G
|
|
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|
|
<br />
|
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|
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SNP: rs587777814,
|
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|
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|
|
ClinVar: RCV000003361
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with FKTN-related limb-girdle muscular dystrophy and normal intelligence (MDDGC4; 611588), Godfrey et al. (2006) identified compound heterozygosity a 1-bp deletion (1363delG) in exon 10 of the FKTN gene, resulting in a frameshift at asp455 and premature termination, and a 1-bp insertion (607440.0005). Functional expression studies showed that the 1363delG mutant protein was expressed and localized correctly within the cell. </p>
|
|
</span>
|
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</div>
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<div>
|
|
<br />
|
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</div>
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</div>
|
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|
<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 4, INCLUDED
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, ARG307GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119463992,
|
|
|
|
|
|
gnomAD: rs119463992,
|
|
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|
|
|
ClinVar: RCV000003362, RCV000724028, RCV001036532, RCV001192872, RCV001254647, RCV003466793, RCV004991964, RCV005041974
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with FKTN-related limb-girdle muscular dystrophy (MDDGC4; 611588) without mental retardation, Godfrey et al. (2006) identified compound heterozygosity for a 920G-A transition in exon 8 of the FKTN gene, resulting in an arg307-to-gln (R307Q) substitution, and a 1-bp insertion (607440.0005). Functional expression studies showed that the R307Q mutant protein was expressed and localized correctly within the cell. </p><p>Mercuri et al. (2009) identified compound heterozygosity for 2 mutations in the FKTN gene (R307Q and 42delG; 607440.0019) in 1 of 81 Italian patients with congenital muscular dystrophy (MDDGB4; 613152) associated with defective glycosylation of alpha-dystroglycan. The patient did not have mental retardation and had no structural brain abnormalities. </p><p>Vuillaumier-Barrot et al. (2009) identified a homozygous R307Q mutation in a Turkish girl with a moderately severe form of muscular dystrophy. She had delayed motor development, pes equinovarus, increased serum creatine kinase, generalized proximal muscle weakness, and diffuse muscle wasting of the calves. The disorder was progressive, and she lost ambulation at 11 years and developed contractures. Intelligence and brain MRI were normal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CARDIOMYOPATHY, DILATED, 1X</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, GLN358PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119463993,
|
|
|
|
|
|
|
|
ClinVar: RCV000003364
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old Japanese man and his 33-year-old sister with dilated cardiomyopathy (CMD1X; 611615), Murakami et al. (2006) identified compound heterozygosity for 2 mutations in the FKTN gene: the 3-kb retroposon insertion (607440.0001) and a 1073A-C transversion, resulting in a gln358-to-pro (Q358P) substitution at a highly conserved residue. The brother was diagnosed with idiopathic dilated cardiomyopathy and congestive heart failure at 17 years of age and underwent cardiac transplantation at age 18; he began having slowly progressive proximal muscle weakness of the lower extremities at 24 years of age, and by age 30, he had calf hypertrophy, Gowers sign, and mild waddling gait. His sister was noted to have cardiomegaly on chest x-ray at age 20, but had no symptoms until 27 years of age, when she developed rapidly progressive heart failure during pregnancy; after induced abortion, her cardiac function recovered and she remained asymptomatic. The unaffected parents were each heterozygous for 1 of the mutations, respectively, and the missense mutation was not found in 100 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CARDIOMYOPATHY, DILATED, 1X</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, ARG179THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119463994,
|
|
|
|
|
|
gnomAD: rs119463994,
|
|
|
|
|
|
ClinVar: RCV000003365, RCV000441410, RCV002512702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese brother and sister and 2 unrelated Japanese women with dilated cardiomyopathy (CMD1X; 611615), Murakami et al. (2006) identified compound heterozygosity for 2 mutations in the FKTN gene: the 3-kb retroposon insertion (607440.0001) and a 536G-C transversion resulting in an arg179-to-thr (R179T) substitution at a highly conserved residue. The brother was a swimmer with no muscle weakness or calf hypertrophy. He developed dyspnea at 12 years of age, was diagnosed with cardiomyopathy, and died within a month from heart failure; autopsy revealed severe CMD with lymphocytic infiltration and fibrosis. His 22-year-old sister was diagnosed with cardiomyopathy at 11 years of age and was noted to have calf hypertrophy, but remained asymptomatic with no muscle weakness. The 2 unrelated Japanese women were diagnosed with CMD at ages 46 and 30 years, respectively; the former had mild proximal muscle weakness without facial muscle involvement, and the latter was noted to have proximal muscle weakness with a waddling gait. The unaffected parents of the brother and sister were each heterozygous for 1 of the mutations, respectively, and the missense mutation was not found in 100 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, GLY125SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs34006675,
|
|
|
|
|
|
gnomAD: rs34006675,
|
|
|
|
|
|
ClinVar: RCV000003366, RCV000079434, RCV000460207, RCV000620119, RCV001794430
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled WALKER-WARBURG SYNDROME, FKTN-RELATED, has been reclassified based on the findings of Bell et al. (2011). </p><p>In a Spanish female infant diagnosed with Walker-Warburg syndrome (MDDGA4; 253800), who died at day 5 of life, Cotarelo et al. (2008) identified compound heterozygosity for a 373G-A transition in exon 5 of the FKTN gene, resulting in a gly125-to-ser (G125S) substitution, and a 473-bp deletion in exon 10 of the FKTN gene (607440.0013) that includes the polyadenylation signal. The patient was not a carrier of the founder retrotransposal insertion (607440.0001). </p><p>In a preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, Bell et al. (2011) found that the G125S mutation in FKTN is a polymorphism carried by unaffected individuals. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, 473-BP DEL, NT5370
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000003367
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 473-bp deletion in exon 10 of the FKTN gene, which included the polyadenylation signal, that was found in compound heterozygous state in a patient diagnosed with Walker-Warburg syndrome (MDDGA4; 253800) by Cotarelo et al. (2008), see 607440.0012. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FKTN, ALA114THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119463995,
|
|
|
|
|
|
|
|
ClinVar: RCV000003368, RCV000675045, RCV001851612
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 brothers of Japanese and Caucasian ancestry with limb-girdle muscular dystrophy (MDDGC4; 611588), Puckett et al. (2009) identified compound heterozygosity for 2 mutations in the FKTN gene: a 340G-A transition in exon 4, resulting in an ala114-to-thr (A114T) substitution, and a 527T-C transition in exon 5, resulting in a phe176-to-ser (F176S; 607440.0015) substitution. The A114T mutation was previously found in 2 sibs with a similar presentation (Godfrey et al., 2007). The F176S mutation, which occurs in a highly conserved residue, was not found in 90 control individuals. The A114T mutation was inherited from the Caucasian father, and the F176S mutation was inherited from the Japanese mother; both parents were unaffected. The phenotype was relatively mild, and there was no cardiac or cognitive involvement. Skeletal muscle biopsy showed defective glycosylation of alpha-dystroglycan. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0015 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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FKTN, PHE176SER
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<br />
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SNP: rs119463996,
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ClinVar: RCV000003358, RCV000626166
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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 527T-C transition in exon 5 of the FKTN gene, resulting in a phe176-to-ser (F176S; 607440.0015) substitution, that was found in compound heterozygous state in 2 brothers of Japanese and Caucasian ancestry with limb-girdle muscular dystrophy (MDDGC4; 611588) by Puckett et al. (2009), see 607440.0014. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0016 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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FKTN, ALA170GLU
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<br />
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SNP: rs119464997,
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gnomAD: rs119464997,
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ClinVar: RCV000003369, RCV003472964, RCV003591619
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|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Portuguese sisters with Fukuyama congenital muscular dystrophy (MDDGA4; 253800), Vuillaumier-Barrot et al. (2009) identified compound heterozygosity for 2 mutations in the FKTN gene: 509C-A transversion in exon 5 of the FKTN gene, resulting in an ala170-to-gly (A170E) substitution, and a 1112A-G transition in exon 9, resulting in a tyr371-to-cys (Y371C; 607440.0017) substitution. Both girls had a severe phenotype, with congenital muscular dystrophy, joint contracture, respiratory insufficiency, and mental retardation. </p><p>Using human mutant FKTN constructs with expression in mouse myoblasts, Tachikawa et al. (2012) found that the A170E and Y371C mutant proteins showed aberrant accumulation in the endoplasmic reticulum due to protein misfolding and failure of the anterograde pathway, in contrast to wildtype FKTN which localized to the Golgi apparatus. Expression studies in Fktn-null mouse embryonic cells showed that the mutant proteins retained normal glycosylation activity, indicating that these disease-causing mutations are pathogenic due to abnormal folding and localization. Low-temperature culture or treatment with curcumin variably corrected the subcellular localization of the missense mutant proteins. </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>.0017 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</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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FKTN, TYR371CYS
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<br />
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SNP: rs119464998,
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gnomAD: rs119464998,
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ClinVar: RCV000003370, RCV000554503, RCV002433443, RCV003466794, RCV004566677, RCV005041975
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|
</span>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1112A-G transition in exon 9 of the FKTN gene, resulting in a tyr371-to-cys (Y371C) substitution, that was found in compound heterozygous state in 2 Portuguese sisters with Fukuyama congenital muscular dystrophy (MDDGA4; 253800) by Vuillaumier-Barrot et al. (2009), see 607440.0016. </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>.0018 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4</strong>
|
|
</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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FKTN, ARG307TER
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<br />
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SNP: rs267606814,
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gnomAD: rs267606814,
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ClinVar: RCV000003371, RCV000498134, RCV000795218, RCV002444418, RCV003466795, RCV004819203, RCV005003319
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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 Walker-Warburg syndrome (MDDGA4; 253800), Godfrey et al. (2007) identified a homozygous 919C-T transition in exon 8 of the FKTN gene, resulting in an arg307-to-ter (R307X) substitution. The patient was 1 of 92 patients with a dystroglycanopathy. Although clinical details were limited, the patient had neonatal onset, contractures, muscle hypertrophy, and increased serum creatine kinase. Eye abnormalities included retinal detachment and microphthalmia. Brain MRI showed cerebellar hypoplasia, white matter abnormalities, hydrocephalus, and brainstem involvement. </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>.0019 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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FKTN, 1-BP DEL, 42G
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|
<br />
|
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|
|
SNP: rs1309132512,
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|
|
ClinVar: RCV000671524, RCV000800445, RCV002282313
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (42delG) in the FKTN gene that was found in compound heterozygous state in a patient with congenital muscular dystrophy-dystroglycanopathy (MDDGB4; 613152) by Mercuri et al. (2009), see 607440.0009. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
|
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
|
|
<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
|
|
Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 21228398]
|
|
|
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|
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[Full Text: https://doi.org/10.1126/scitranslmed.3001756]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Beltran-Valero de Bernabe, D., van Bokhoven, H., van Beusekom, E., Van den Akker, W., Kant, S., Dobyns, W. B., Cormand, B., Currier, S., Hamel, B., Talim, B., Topaloglu, H., Brunner, H. G.
|
|
<strong>A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype.</strong>
|
|
J. Med. Genet. 40: 845-848, 2003.
|
|
|
|
|
|
[PubMed: 14627679]
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|
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[Full Text: https://doi.org/10.1136/jmg.40.11.845]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Colombo, R., Bignamini, A. A., Carobene, A., Sasaki, J., Tachikawa, M., Kobayashi, K., Toda, T.
|
|
<strong>Age and origin of the FCMD 3-prime-untranslated-region retrotransposal insertion mutation causing Fukuyama-type congenital muscular dystrophy in the Japanese population.</strong>
|
|
Hum. Genet. 107: 559-567, 2000.
|
|
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|
|
|
[PubMed: 11153909]
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|
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[Full Text: https://doi.org/10.1007/s004390000421]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Cotarelo, R. P., Valero, M. C., Prados, B., Pena, A., Rodriguez, L., Fano, O., Marco, J. J., Martinez-Frias, M. L., Cruces, J.
|
|
<strong>Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.</strong>
|
|
Clin. Genet. 73: 139-145, 2008.
|
|
|
|
|
|
[PubMed: 18177472]
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|
|
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|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00936.x]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
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: 12471058]
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|
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[Full Text: https://doi.org/10.1093/hmg/11.26.3319]
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</p>
|
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Godfrey, C., Clement, E., Mein, R., Brockington, M., Smith, J., Talim, B., Straub, V., Robb, S., Quinlivan, R., Feng, L., Jimenez-Mallebrera, C., Mercuri, E., and 10 others.
|
|
<strong>Refining genotype-phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.</strong>
|
|
Brain 130: 2725-2735, 2007.
|
|
|
|
|
|
[PubMed: 17878207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awm212]
|
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|
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Godfrey, C., Escolar, D., Brockington, M., Clement, E. M., Mein, R., Jimenez-Mallebrera, C., Torelli, S., Feng, L., Brown, S. C., Sewry, C. A., Rutherford, M., Shapira, Y., Abbs, S., Muntoni, F.
|
|
<strong>Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.</strong>
|
|
Ann. Neurol. 60: 603-610, 2006.
|
|
|
|
|
|
[PubMed: 17044012]
|
|
|
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|
|
[Full Text: https://doi.org/10.1002/ana.21006]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hayashi, Y. K., Ogawa, M., Tagawa, K., Noguchi, S., Ishihara, T., Nonaka, I., Arahata, K.
|
|
<strong>Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.</strong>
|
|
Neurology 57: 115-121, 2001.
|
|
|
|
|
|
[PubMed: 11445638]
|
|
|
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|
|
[Full Text: https://doi.org/10.1212/wnl.57.1.115]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Miyagoe-Suzuki, Y., Wang, F., Fujikake, N., Taniguchi, M., Lu, Z., Tachikawa, M., Nagai, Y., Tashiro, F., Miyazaki, J., Tajima, Y., Takeda, S., Endo, T., Kobayashi, K., Campbell, K. P., Toda, T.
|
|
<strong>Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.</strong>
|
|
Hum. Molec. Genet. 18: 621-631, 2009.
|
|
|
|
|
|
[PubMed: 19017726]
|
|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddn387]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kato, R., Kawamura, J., Sugawara, H., Niikawa, N., Matsumoto, N.
|
|
<strong>A rapid diagnostic method for a retrotransposal insertional mutation into the FCMD gene in Japanese patients with Fukuyama congenital muscular dystrophy.</strong>
|
|
Am. J. Med. Genet. 127A: 54-57, 2004.
|
|
|
|
|
|
[PubMed: 15103718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20669]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M., Yoshioka, M., Saito, K., Osawa, M., Hamano, K., Sakakihara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y., Tokunaga, K., Toda, T.
|
|
<strong>An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.</strong>
|
|
Nature 394: 388-392, 1998.
|
|
|
|
|
|
[PubMed: 9690476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/28653]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kondo-Iida, E., Kobayashi, K., Watanabe, M., Sasaki, J., Kumagai, T., Koide, H., Saito, K., Osawa, M., Nakamura, Y., Toda, T.
|
|
<strong>Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).</strong>
|
|
Hum. Molec. Genet. 8: 2303-2309, 1999.
|
|
|
|
|
|
[PubMed: 10545611]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.12.2303]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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: 19299310]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000346518.68110.60]
|
|
|
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|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y., Ogino, M., Takada, F., Eriguchi, M., Kotooka, N., Campbell, K. P., Osawa, M., Nishino, I.
|
|
<strong>Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.</strong>
|
|
Ann. Neurol. 60: 597-602, 2006.
|
|
|
|
|
|
[PubMed: 17036286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20973]
|
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|
</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Puckett, R. L., Moore, S. A., Winder, T. L., Willer, T., Romansky, S. G., Covault, K. K., Campbell, K. P., Abdenur, J. E.
|
|
<strong>Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.</strong>
|
|
Neuromusc. Disord. 19: 352-356, 2009.
|
|
|
|
|
|
[PubMed: 19342235]
|
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|
|
[Full Text: https://doi.org/10.1016/j.nmd.2009.03.001]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Saito, K., Osawa, M., Wang, Z.-P., Ikeya, K., Fukuyama, Y., Kondo-Iida, E., Toda, T., Ohashi, H., Kurosawa, K., Wakai, S., Kaneko, K.
|
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Sasaki, J., Ishikawa, K., Kobayashi, K., Kondo-Iida, E., Fukayama, M., Mizusawa, H., Takashima, S., Sakakihara, Y., Nakamura, Y., Toda, T.
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Silan, F., Yoshioka, M., Kobayashi, K., Simsek, E., Tunc, M., Alper, M., Cam, M., Guven, A., Fukuda, Y., Kinoshita, M., Kocabay, K., Toda, T.
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<strong>A new mutation of the fukutin gene in a non-Japanese patient.</strong>
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Ann. Neurol. 53: 392-396, 2003.
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Tachikawa, M., Kanagawa, M., Yu, C.-C., Kobayashi, K., Toda, T.
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<strong>Mislocalization of fukutin protein by disease-causing missense mutations can be rescued with treatments directed at folding amelioration.</strong>
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J. Biol. Chem. 287: 8398-8406, 2012.
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Takeda, S., Kondo, M., Sasaki, J., Kurahashi, H., Kano, H., Arai, K., Misaki, K., Fukui, T., Kobayashi, K., Tachikawa, M., Imamura, M., Nakamura, Y., Shimizu, T., Murakami, T., Sunada, Y., Fujikado, T., Matsumura, K., Terashima, T., Toda, T.
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<strong>Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development.</strong>
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Hum. Molec. Genet. 12: 1449-1459, 2003.
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[PubMed: 12783852]
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[Full Text: https://doi.org/10.1093/hmg/ddg153]
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Taniguchi-Ikeda, M., Kobayashi, K., Kanagawa, M., Yu, C., Mori, K., Oda, T., Kuga, A., Kurahashi, H., Akman, H. O., DiMauro, S., Kaji, R., Yokota, T., Takeda, S., Toda, T.
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<strong>Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.</strong>
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Toda, T., Miyake, M., Kobayashi, K., Mizuno, K., Saito, K., Osawa, M., Nakamura, Y., Kanazawa, I., Nakagome, Y., Yokunaga, K., Nakahori, Y.
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<strong>Linkage-disequilibrium mapping narrows the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region to less than 100 kb.</strong>
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Am. J. Hum. Genet. 59: 1313-1320, 1996.
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[PubMed: 8940277]
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Vuillaumier-Barrot, S., Quijano-Roy, S., Bouchet-Seraphin, C., Maugenre, S., Peudenier, S., Van den Bergh, P., Marcorelles, P., Avila-Smirnow, D., Chelbi, M., Romero, N. B., Carlier, R. Y., Estournet, B., Guicheney, P., Seta, N.
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<strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong>
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Watanabe, M., Kobayashi, K., Jin, F., Park, K. S., Yamada, T., Tokunaga, K., Toda, T.
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<strong>Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations.</strong>
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[PubMed: 16222679]
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Xiong, H., Wang, S., Kobayashi, K., Jiang, Y., Wang, J., Chang, X., Yuan, Y., Liu, J., Toda, T., Fukuyama, Y., Wu, X.
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<strong>Fukutin gene retrotransposal insertion in a non-Japanese Fukuyama congenital muscular dystrophy (FCMD) patient.</strong>
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[PubMed: 19842201]
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[Full Text: https://doi.org/10.1002/ajmg.a.33057]
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Cassandra L. Kniffin - updated : 6/13/2012<br>Ada Hamosh - updated : 1/10/2012<br>Cassandra L. Kniffin - updated : 2/10/2011<br>Cassandra L. Kniffin - updated : 12/4/2009<br>Cassandra L. Kniffin - updated : 10/27/2009<br>George E. Tiller - updated : 8/10/2009<br>Marla J. F. O'Neill - updated : 7/10/2008<br>Marla J. F. O'Neill - updated : 11/26/2007<br>Cassandra L. Kniffin - updated : 11/7/2007<br>Victor A. McKusick - updated : 2/8/2007<br>Cassandra L. Kniffin - updated : 3/9/2006<br>George E. Tiller - updated : 3/21/2005<br>Victor A. McKusick - updated : 5/26/2004<br>Cassandra L. Kniffin - updated : 1/6/2004<br>Cassandra L. Kniffin - updated : 5/7/2003
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