4630 lines
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4630 lines
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Entry
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- #253800 - MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4
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<p>
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<span class="h4">#253800</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/253800"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS236670"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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 id="mimExternalLinksFold" class="collapse in">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" 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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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in 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://clinicaltrials.gov/search?cond=MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=8724&Typ=Pat" title="Congenital muscular dystrophy, Fukuyama type" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Congenital muscular dystro… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=8726&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Muscle-eye-brain disease </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=8725&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Walker-Warburg syndrome </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1206/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/2962" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/fukuyama-congenital-muscular-dystrophy" 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=253800[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><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=272" title="Congenital muscular dystrophy, Fukuyama type" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Congenital muscular dystro…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Muscle-eye-brain disease</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Walker-Warburg syndrome</a></div>
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</div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/5037de26-1a33-4c77-9792-006460bf9ce8/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<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/disease/DOID:0050559" 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="http://www.informatics.jax.org/disease/253800" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050559" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:253800" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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<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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<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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<a id="title" class="mim-anchor"></a>
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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<br />
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<strong>ORPHA:</strong> 272, 588, 899<br />
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<strong>DO:</strong> 0050559<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="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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253800
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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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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4
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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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FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY; FCMD<br />
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WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, FKTN-RELATED
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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="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/9/389?start=-3&limit=10&highlight=389">
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9q31.2
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 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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<a href="/entry/253800"> 253800 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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FKTN
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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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<a href="/entry/607440"> 607440 </a>
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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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|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/253800" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
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</div>
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<div class="btn-group">
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|
|
<a href="/phenotypicSeries/PS236670" class="btn btn-info" role="button"> Phenotypic Series </a>
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|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/253800" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/253800" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<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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<div>
|
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<p />
|
|
</div>
|
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|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Retinal detachment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42059000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42059000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H33.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H33.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/361.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">361.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035305&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035305</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000541</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000541</a>]</span><br /> -
|
|
Abnormal eye movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103252009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103252009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0497202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497202</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span><br /> -
|
|
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
|
|
Myopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57190000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57190000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027092&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027092</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span><br /> -
|
|
Hyperopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38101003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38101003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span><br /> -
|
|
Cataracts <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span><br /> -
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Microphthalmia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204108000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204108000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61142002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61142002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q11.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q11.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/743.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">743.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/743.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">743.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/743.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">743.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026010&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026010</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000568" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000568</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000568" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000568</a>]</span><br /> -
|
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Retinal dysplasia (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95494009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95494009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035313&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035313</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007973" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007973</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007973" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007973</a>]</span><br />
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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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<span class="h5 mim-font">
|
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<strong> CARDIOVASCULAR </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Heart </em>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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|
- Myocardial fibrosis <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151654</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001685" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001685</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001685" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001685</a>]</span><br /> -
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Dilated cardiomyopathy (onset in second decade) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278515&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278515</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399020009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399020009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195021004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195021004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.0</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001644" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001644</a>]</span><br /> -
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Cardiac defects (reported in 1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0741916&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0741916</a>]</span><br /> -
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Atrial septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
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Double subaortic ventricular defect <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278517&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278517</a>]</span><br /> -
|
|
Hypoplastic left ventricular outlet <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278518&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278518</a>]</span><br /> -
|
|
Pulmonary stenosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56786000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56786000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1956257&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1956257</a>, <a href="https://bioportal.bioontology.org/search?q=C0034089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001642</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001642</a>]</span><br /> -
|
|
Transposition of the great arteries <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26146002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26146002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q20.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q20.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/745.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040761</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001669" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001669</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001669" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001669</a>]</span><br />
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|
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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>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Respiratory insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1145670&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1145670</a>, <a href="https://bioportal.bioontology.org/search?q=C0035229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035229</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Contractures, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278514</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57048009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57048009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55033002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55033002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.4</a>]</span><br />
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</span>
|
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Spinal rigidity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858025&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858025</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span><br /> -
|
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Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br />
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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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<span class="h5 mim-font">
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<strong> MUSCLE, SOFT TISSUES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Muscular dystrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/73297009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">73297009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G71.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G71.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026850&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026850</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003560" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003560</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003560" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003560</a>]</span><br /> -
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Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
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Muscle atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br /> -
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Calf muscle hypertrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843057&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843057</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008981" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008981</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008981" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008981</a>]</span><br /> -
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Muscle biopsy shows decreased glycosylation of alpha-dystroglycan (DAG1, <a href="/entry/128239">128239</a>)<br />
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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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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
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Poor motor development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278510</a>]</span><br /> -
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|
Polymicrogyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4945003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4945003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266464</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span><br /> -
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Leptomeningeal thickening <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850867&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850867</a>]</span><br /> -
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|
Focal interhemispheric fusion <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850868&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850868</a>]</span><br /> -
|
|
Low density white matter on CT scan <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850869&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850869</a>]</span><br /> -
|
|
Cobblestone lissencephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253149002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253149002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431376</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007260</a>]</span><br /> -
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Pachygyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23024003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23024003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.8</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266483&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266483</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001302" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001302</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001302" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001302</a>]</span><br /> -
|
|
Polymicrogyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4945003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4945003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266464</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span><br /> -
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Agyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204036008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204036008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1879312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1879312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031882</a>]</span><br /> -
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|
Agenesis of the corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5102002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5102002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0175754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0175754</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span><br /> -
|
|
Encephalocele (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48777005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48777005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55999004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55999004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253101008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253101008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q01.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q01.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q01</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014065&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014065</a>, <a href="https://bioportal.bioontology.org/search?q=C4551722&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551722</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011815" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011815</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002084</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002084</a>]</span><br /> -
|
|
Hydrocephalus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020255&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020255</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br /> -
|
|
Cerebellar cysts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847762</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002350" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002350</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002350" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002350</a>]</span><br /> -
|
|
White matter changes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833300&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833300</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
|
Hyperekplexia (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19557000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19557000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234166&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234166</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002267</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002267</a>]</span><br /> -
|
|
Pyramidal tract hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850871</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007348</a>]</span><br /> -
|
|
Brainstem hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842688&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842688</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002365</a>]</span><br /> -
|
|
Cerebellar hypoplasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16026008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16026008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266470&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266470</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001321" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001321</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001321" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001321</a>]</span><br /> -
|
|
Holoprosencephaly (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30915001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30915001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0079541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0079541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001360</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001360</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
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</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypo- or areflexia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2676663&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2676663</a>]</span><br />
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|
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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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<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241005&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241005</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
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|
|
- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
|
|
Incidence of 1 per 10,000 births in Japan<br />
|
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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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<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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|
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<div>
|
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<span class="mim-font">
|
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|
|
- Caused by mutation in the fukutin gene (FKTN, <a href="/entry/607440#0001">607440.0001</a>)<br />
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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 class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
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</div>
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</div>
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|
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Muscular dystrophy-dystroglycanopathy, type A
|
|
- <a href="/phenotypicSeries/PS236670">PS236670</a>
|
|
- 14 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
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|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/565?start=-3&limit=10&highlight=565"> 1p34.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/253280"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/253280"> 253280 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606822"> POMGNT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606822"> 606822 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1818?start=-3&limit=10&highlight=1818"> 1q42.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615181"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615181"> 615181 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610194"> B3GALNT2 </a>
|
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</span>
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<span class="mim-font">
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<a href="/entry/610194"> 610194 </a>
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<span class="mim-font">
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<a href="/geneMap/3/214?start=-3&limit=10&highlight=214"> 3p22.1 </a>
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<span class="mim-font">
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<a href="/entry/614830"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/614830"> 614830 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/614828"> POMGNT2 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/614828"> 614828 </a>
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</span>
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<span class="mim-font">
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<a href="/geneMap/3/313?start=-3&limit=10&highlight=313"> 3p21.31 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/616538"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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<a href="/entry/616538"> 616538 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/128239"> DAG1 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/128239"> 128239 </a>
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</span>
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<span class="mim-font">
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<a href="/geneMap/3/319?start=-3&limit=10&highlight=319"> 3p21.31 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615350"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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<a href="/entry/615350"> 615350 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615320"> GMPPB </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615320"> 615320 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/geneMap/7/83?start=-3&limit=10&highlight=83"> 7p21.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/614643"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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<a href="/entry/614643"> 614643 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/614631"> CRPPA </a>
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</span>
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</td>
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<span class="mim-font">
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<a href="/entry/614631"> 614631 </a>
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/8/243?start=-3&limit=10&highlight=243"> 8p11.21 </a>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/615249"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/615249"> 615249 </a>
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615247"> POMK </a>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615247"> 615247 </a>
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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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<a href="/geneMap/9/389?start=-3&limit=10&highlight=389"> 9q31.2 </a>
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</span>
|
|
</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/253800"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/253800"> 253800 </a>
|
|
</span>
|
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</td>
|
|
<td>
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<span class="mim-font">
|
|
<a href="/entry/607440"> FKTN </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607440"> 607440 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/589?start=-3&limit=10&highlight=589"> 9q34.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/236670"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/236670"> 236670 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607423"> POMT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607423"> 607423 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/633?start=-3&limit=10&highlight=633"> 11q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615287"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615287"> 615287 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605517"> B4GAT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605517"> 605517 </a>
|
|
</span>
|
|
</td>
|
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</tr>
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|
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/577?start=-3&limit=10&highlight=577"> 12q14.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615041"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615041"> 615041 </a>
|
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</span>
|
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</td>
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|
<td>
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<span class="mim-font">
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<a href="/entry/605862"> RXYLT1 </a>
|
|
</span>
|
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</td>
|
|
<td>
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<span class="mim-font">
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|
<a href="/entry/605862"> 605862 </a>
|
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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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|
|
|
<a href="/geneMap/14/414?start=-3&limit=10&highlight=414"> 14q24.3 </a>
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613150"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613150"> 613150 </a>
|
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</span>
|
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</td>
|
|
<td>
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<span class="mim-font">
|
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<a href="/entry/607439"> POMT2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607439"> 607439 </a>
|
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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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|
|
<a href="/geneMap/19/859?start=-3&limit=10&highlight=859"> 19q13.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613153"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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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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</span>
|
|
</td>
|
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<td>
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<span class="mim-font">
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<a href="/entry/613153"> 613153 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/606596"> FKRP </a>
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/606596"> 606596 </a>
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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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<a href="/geneMap/22/207?start=-3&limit=10&highlight=207"> 22q12.3 </a>
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</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/613154"> Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<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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</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
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<a href="/entry/613154"> 613154 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603590"> LARGE1 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603590"> 603590 </a>
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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 class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<p>A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A4; MDDGA4), previously designated Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), or muscle-eye-brain disease (MEB), is caused by homozygous or compound heterozygous mutation in the gene encoding fukutin (FKTN; <a href="/entry/607440">607440</a>) on chromosome 9q31.</p><p>Mutation in the FKTN gene can also cause a less severe congenital muscular dystrophy-dystroglycanopathy without impaired intellectual development (type B4; MDDGB4; <a href="/entry/613152">613152</a>) and a limb-girdle muscular dystrophy-dystroglycanopathy (type C4; MDDGC4; <a href="/entry/611588">611588</a>).</p>
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<p>MDDGA4 is a severe autosomal recessive muscular dystrophy-dystroglycanopathy with characteristic brain and eye malformations, seizures, and mental retardation. Cardiac involvement in FCMD/MEB occurs in the second decade of life in those who survive. FKTN-related Walker-Warburg syndrome is a more severe manifestation of the disorder, with death usually in the first year of life. These entities are part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>), collectively known as 'dystroglycanopathies' (<a href="#8" 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>; <a href="#19" class="mim-tip-reference" title="Muntoni, F., Voit, T. <strong>The congenital muscular dystrophies in 2004: a century of exciting progress.</strong> Neuromusc. Disord. 14: 635-649, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15351421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15351421</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.06.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15351421">Muntoni and Voit, 2004</a>; <a href="#18" class="mim-tip-reference" title="Muntoni, F., Torelli, S., Brockington, M. <strong>Muscular dystrophies due to glycosylation defects.</strong> Neurotherapeutics 5: 627-632, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19019316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19019316</a>] [<a href="https://doi.org/10.1016/j.nurt.2008.08.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19019316">Muntoni et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15351421+17878207+19019316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (<a href="/entry/236670">236670</a>).</p>
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<p>This disorder has been described as FCMD/muscle-eye-brain disease (MEB) and the more severe Walker-Warburg syndrome; these designations have been retained here when used in the literature.</p><p><strong><em>Fukuyama Congenital Muscular Dystrophy/FKTN-Related Muscle-Eye-Brain Disease</em></strong></p><p>
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<a href="#6" class="mim-tip-reference" title="Fukuyama, Y., Kawazura, M., Haruna, H. <strong>A peculiar form of congenital progressive muscular dystrophy: report of fifteen cases.</strong> Paediat. Univ. Tokyo 4: 5-8, 1960."None>Fukuyama et al. (1960)</a> described a novel form of congenital muscular dystrophy. Parental consanguinity was present in 6 families; in 2 sibships, multiple cases were observed. <a href="#7" class="mim-tip-reference" title="Fukuyama, Y., Osawa, M., Suzuki, H. <strong>Congenital progressive muscular dystrophy of the Fukuyama type--clinical, genetic and pathological considerations.</strong> Brain Dev. 3: 1-30, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258547</a>] [<a href="https://doi.org/10.1016/s0387-7604(81)80002-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7258547">Fukuyama et al. (1981)</a> stated that more than 200 cases had been recognized clinically in Japan. Patients manifest generalized muscle weakness and hypotonia from early infancy and most are unable to walk without support. All are mentally retarded and some have seizures, abnormal electroencephalograms, and abnormal CT scans. The brain malformations in FCMD include cerebral and cerebellar micropolygyria, fibroglial proliferation of the leptomeninges, hydrocephalus, focal interhemispheric fusion, and hypoplasia of the corticospinal tracts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7258547" 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>Histologic changes in skeletal muscle were similar to those of Duchenne muscular dystrophy (DMD; <a href="/entry/310200">310200</a>) (<a href="#22" class="mim-tip-reference" title="Nonaka, I., Sugita, H., Takada, K., Kumagai, K. <strong>Muscle histochemistry in congenital muscular dystrophy with central nervous system involvement.</strong> Muscle Nerve 5: 102-106, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6461828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6461828</a>] [<a href="https://doi.org/10.1002/mus.880050204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6461828">Nonaka et al., 1982</a>). Caucasian patients were studied by <a href="#5" class="mim-tip-reference" title="Dambska, M., Wisniewski, K., Sher, J., Solish, G. <strong>Cerebro-oculo-muscular syndrome: a variant of Fukuyama congenital cerebro-muscular dystrophy.</strong> Clin. Neuropath. 1: 93-98, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6820333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6820333</a>]" pmid="6820333">Dambska et al. (1982)</a>. <a href="#16" class="mim-tip-reference" title="Miura, K., Shirasawa, H. <strong>Congenital muscular dystrophy of the Fukuyama type (FCMD) with severe myocardial fibrosis: a case report with postmortem angiography.</strong> Acta Path. Jpn. 37: 1823-1835, 1987."None>Miura and Shirasawa (1987)</a> described severe myocardial fibrosis in the autopsy of a 17-year-old Japanese male. <a href="#1" class="mim-tip-reference" title="Aida, N., Yagishita, A., Takada, K., Katsumata, Y. <strong>Cerebellar MR in Fukuyama congenital muscular dystrophy: polymicrogyria with cystic lesions.</strong> Am. J. Neuroradiol. 15: 1755-1759, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847224</a>]" pmid="7847224">Aida et al. (1994)</a> demonstrated cerebellar polymicrogyria and the presence of cerebellar cysts related to the polymicrogyria in 23 of 25 patients with congenital muscular dystrophy. These 2 changes on MRI are distinctive enough to suggest the radiologic diagnosis of this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6820333+6461828+7847224" 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="#37" class="mim-tip-reference" title="Yoshioka, M., Kuroki, S. <strong>Clinical spectrum and genetic studies of Fukuyama congenital muscular dystrophy.</strong> Am. J. Med. Genet. 53: 245-250, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7856660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7856660</a>] [<a href="https://doi.org/10.1002/ajmg.1320530309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7856660">Yoshioka and Kuroki (1994)</a> performed clinical and genetic studies in 41 families with FCMD in Japan in an attempt to distinguish it from the Walker-Warburg syndrome and muscle-eye-brain disease, both of which, like FCMD, show an association of type II lissencephaly and ocular anomalies. Two or more children were affected in 9 families. Parental consanguinity was documented in 5 of the 32 sporadic cases and in none of the familial cases. In evaluations of 7 sib pairs, a difference between sibs in motor ability was apparent in 4. Mental status also showed wide variation. The EEG findings differed in 2 of 7 sib pairs. The familial FCMD patients showed relatively more severe motor disability than that in the sporadic FCMD patients, whereas the status in regard to mental function and convulsions showed no significant difference in the 2 groups. In 1 family, hydrocephalus was found in only 1 of the sibs; in addition, this patient showed encephalocele and retinal detachment at birth. <a href="#37" class="mim-tip-reference" title="Yoshioka, M., Kuroki, S. <strong>Clinical spectrum and genetic studies of Fukuyama congenital muscular dystrophy.</strong> Am. J. Med. Genet. 53: 245-250, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7856660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7856660</a>] [<a href="https://doi.org/10.1002/ajmg.1320530309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7856660">Yoshioka and Kuroki (1994)</a> emphasized the broad clinical spectrum of FCMD and the phenotypic overlap with mild WWS and MEB disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7856660" 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="#31" class="mim-tip-reference" title="Toda, T., Yoshioka, M., Nakahori, Y., Kanazawa, I., Nakamura, Y., Nakagome, Y. <strong>Genetic identity of Fukuyama-type congenital muscular dystrophy and Walker-Warburg syndrome.</strong> Ann. Neurol. 37: 99-101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7818265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7818265</a>] [<a href="https://doi.org/10.1002/ana.410370118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7818265">Toda et al. (1995)</a> used polymorphic microsatellites flanking the FCMD locus on 9q31-q33 (see MAPPING) to study a family in which 3 sibs were affected with either FCMD or WWS. One sib was labeled as FCMD because he showed severe hypotonia with dystrophic findings on a muscle biopsy, in addition to pachygyria on computed tomographic scan. At age 3 years, the patient developed retinal detachment in both eyes. The second pregnancy resulted in a male infant with anencephaly who survived for 5 minutes. At birth, the third sib exhibited pachygyria, cephalocele, hydrocephalus, bilateral retinal detachment, elevated serum creatine kinase, and arthrogryposis multiplex congenita, all features consistent with Walker-Warburg syndrome. Haplotype analysis demonstrated identity of each allele in the 2 surviving sibs. The parents were nonconsanguineous, and the disease-related haplotypes were different on the 2 alleles of the patients. <a href="#31" class="mim-tip-reference" title="Toda, T., Yoshioka, M., Nakahori, Y., Kanazawa, I., Nakamura, Y., Nakagome, Y. <strong>Genetic identity of Fukuyama-type congenital muscular dystrophy and Walker-Warburg syndrome.</strong> Ann. Neurol. 37: 99-101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7818265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7818265</a>] [<a href="https://doi.org/10.1002/ana.410370118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7818265">Toda et al. (1995)</a> presented this as evidence that the 2 disorders may be allelic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7818265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="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 1 patient with FKTN-related FCMD/MEB among a larger study of 92 probands with muscular dystrophy and evidence of a dystroglycanopathy. Although clinical details were limited, the patient had infantile onset, muscle hypertrophy, increased serum creatine kinase, and low IQ. He only achieved sitting. There were no eye abnormalities, but brain MRI showed cerebellar cysts, white matter abnormalities, and hydrocephalus. As part of the larger study, <a href="#8" 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> defined FCMD/MEB as congenital onset of muscular dystrophy with fronto-parietal pachygyria, cerebellar dysplasia, and frequent flattening of the pons and brainstem. Eye abnormalities are often seen, and rare patients may acquire the ability to walk or learn a few words. <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="#34" 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> reported 2 Portuguese sisters with mental retardation and muscular dystrophy associated with compound heterozygous mutations in the FKTN gene (A170E, <a href="/entry/607440#0016">607440.0016</a>; Y371C, <a href="/entry/607440#0017">607440.0017</a>). Both had congenital hip dislocation, congenital hypotonia, and delayed motor development. Muscle weakness was diffuse and progressive with axial and proximal limb predominance and moderate facial involvement; both had significantly increased serum creatine kinase. One sister lost the ability to walk in the first decade of life and developed multiple contractures and severe respiratory insufficiency. She was mentally retarded and had epileptic seizures from age 13 years. The other sister had knee contractures from the first year of life, spinal rigidity, and scoliosis. She developed severe and progressive restrictive respiratory insufficiency and nondilated left ventricular dysfunction in her teens. At age 19 years, she had diffuse amyotrophy, severe multiple joint contractures, and a stiff hyperextended neck. Both were mentally retarded, but 1 had significantly better verbal abilities. Brain MRI showed brainstem atrophy, marked cerebellar vermis hypoplasia and cysts, and cortical brain atrophy. One patient had cerebellar polymicrogyria. <a href="#34" 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> commented that few patients outside of Japan had been reported with this disorder. <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><a href="#32" class="mim-tip-reference" title="Tunc, B. T., Mungan, I. A., Okulu, E., Tiras, S. T., Tekin, M., Atasay, B., Arsan, S., Turmen, T. <strong>Hyperekplexia in a neonate: a novel finding in Fukuyama type congenital muscular dystrophy.</strong> Genet. Counsel. 20: 275-279, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19852435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19852435</a>]" pmid="19852435">Tunc et al. (2009)</a> reported a female infant with FCMD, born of consanguineous Turkish parents, who had severe hypotonia and abnormal limb movements. Just after birth, she showed rhythmic and jerky movements of all 4 limbs, both spontaneously and in response to stimulus, but these were associated with a normal EEG. The findings were consistent with hyperekplexia (see HKPX1, <a href="/entry/149400">149400</a>). Brain imaging showed absent corpus callosum, lissencephaly, pachygyria, ventricular dilatation, subcortical white matter abnormalities, and brainstem and cerebellar hypoplasia. She died at day 15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19852435" 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="#36" 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. He showed hypotonia from birth, achieved head control at age 2 years, and sat unsupported at age 4 years, but was unable to slide on his buttocks. He developed progressive knee and ankle contractures after age 1 year. He had facial muscle and generalized muscle weakness with severe muscle atrophy, but hypertrophy of the calf muscle. Brain MRI showed patchy periventricular hyperintensities, frontal lobe polymicrogyria, cerebellar cysts, and cerebellar and brainstem hypoplasia. He had an IQ of 52 and spoke only a few words. Muscle biopsy showed prominent dystrophic features and decreased alpha-dystroglycan staining. Genetic analysis identified compound heterozygosity for 2 mutations in the fukutin gene: the common Japanese founder allele (<a href="/entry/607440#0001">607440.0001</a>) and R47X (<a href="/entry/607440#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>FKTN-Related Walker-Warburg Syndrome</em></strong></p><p>
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<a href="#24" 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> reported a Turkish patient with a severe congenital muscular dystrophy phenotype most closely resembling Walker-Warburg syndrome. 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="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><p><a href="#3" 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 Turkish patient with Walker-Warburg syndrome. Born to second-degree consanguineous parents, the patient had macrocephaly, anterior chamber abnormalities, severe hypotonia, and severe brain malformations, including hydrocephalus, agyria/pachygyria, absent corpus callosum and cerebellar vermis, and white matter hyperlucencies. The patient died at 4.5 months of age. <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><p><a href="#8" 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 1 patient with FKTN-related WWS among a larger study of 92 probands with muscular dystrophy and evidence of 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. As part of the larger study, <a href="#8" 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> defined WWS as prenatal onset or onset of birth of absence of motor development and severe structural brain abnormalities, including complete agyria or severe lissencephaly, marked hydrocephalus, severe cerebellar involvement, and complete or partial absence of the corpus callosum. Common eye abnormalities included congenital cataracts, microphthalmia, and buphthalmos. Death usually occurred before 1 year of age. Genetic analysis identified a homozygous truncating mutation in the FKTN gene (R307X; <a href="/entry/607440#0018">607440.0018</a>). <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="#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> described a Spanish female infant, born of nonconsanguineous parents, who was diagnosed with Walker-Warburg syndrome and died on day 5 of life after suffering respiratory apnea and bradycardia. She had a dysmorphic face with low-set malformed ears, left preauricular tag, thoracic hemivertebrae, and cardiac defects. Brain CT scan showed overriding cranial bones, severe left microphthalmia, monolobar holoprosencephaly, and internal and external hydrocephalus. Cortex and white matter could not be differentiated, and no details could be observed in the posterior fossa. At autopsy, the medial aspect of the brain showed an interhemispheric cyst, incomplete cleavage of the thalamus and corpora quadrigemina, an absent corpus callosum, and rhombencephalic hypoplasia. Punctate hemorrhages were seen in the parenchyma, and ventriculitis was identified. An atrial septal defect (foramen ovale), double subaortic ventricular defect, hypoplastic left ventricle outlet, stenotic pulmonary valve, and infundibular transposition of the great vessels with no innominate vein were also found. The eyes were malformed and exhibited retinal dysplasia. <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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<p>The involvement of multiple sibs of both sexes and parental consanguinity reported by <a href="#6" class="mim-tip-reference" title="Fukuyama, Y., Kawazura, M., Haruna, H. <strong>A peculiar form of congenital progressive muscular dystrophy: report of fifteen cases.</strong> Paediat. Univ. Tokyo 4: 5-8, 1960."None>Fukuyama et al. (1960)</a> supported autosomal recessive inheritance.</p>
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<p><a href="#29" class="mim-tip-reference" title="Toda, T., Kanazawa, I., Nakamura, Y. <strong>Localization of a gene responsible for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33 by linkage analysis. (Abstract)</strong> Human Genome Mapping Workshop 93, Kobe, Japan 1993. P. 20."None>Toda et al. (1993)</a> performed genetic linkage analysis with polymorphic microsatellite markers in 21 FCMD families, 13 of which had consanguineous marriages. Significant lod scores were found with 3 loci on 9q31-q33. Multipoint analysis placed the FCMD gene in the interval between D9S58 and D9S59, with a maximum location score of 39.0. Homozygosity mapping supported the assignment. In a nonconsanguineous sibship in which 1 sib was thought to have FCMD and another sib was thought to have WWS, <a href="#31" class="mim-tip-reference" title="Toda, T., Yoshioka, M., Nakahori, Y., Kanazawa, I., Nakamura, Y., Nakagome, Y. <strong>Genetic identity of Fukuyama-type congenital muscular dystrophy and Walker-Warburg syndrome.</strong> Ann. Neurol. 37: 99-101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7818265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7818265</a>] [<a href="https://doi.org/10.1002/ana.410370118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7818265">Toda et al. (1995)</a> found linkage to the FCMD locus on chromosome 9q31-q33, suggesting that they may be allelic disorders, or at least caused by the same gene in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7818265" 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="#30" 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> refined the map location of FCMD to a 5-cM region between D9S127 and D9S2111. They reported that there is linkage disequilibrium between FCMD and markers in 9q31. Haplotype analysis using the markers D9S2105, D9S2107, and D9S172 indicated that most FCMD-bearing chromosomes in Japanese pedigrees were derived from a single ancestral founder. On the basis of haplotype analysis, <a href="#30" 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 FCMD gene most likely lies on 9q31 within a less than 100-kb region containing the D9S2107 marker. They suggested that the muscle-specific receptor tyrosine kinase gene (MUSK; <a href="/entry/601296">601296</a>) reported by <a href="#33" class="mim-tip-reference" title="Valenzuela, D. M., Stitt, T. N., DiStefano, P. S., Rojas, E., Mattsson, K., Compton, D. L., Nunez, L., Park, J. S., Stark, J. L., Gies, D. R., Thomas, S., Le Beau, M. M., Fernald, A. A., Copeland, N. G., Jenkins, N. A., Burden, S. J., Glass, D. J., Yancopoulos, G. D. <strong>Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle , at the neuromuscular junction, and after injury.</strong> Neuron 15: 573-584, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7546737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7546737</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90146-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7546737">Valenzuela et al. (1995)</a> is a candidate FCMD gene since its map location overlaps with that of FCMD. <a href="#17" class="mim-tip-reference" title="Miyake, M., Nakahori, Y., Matsushita, I., Kobayashi, K., Mizuno, K., Hirai, M., Kanazawa, I., Nakagome, Y., Tokunaga, K., Toda, T. <strong>YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31.</strong> Genomics 40: 284-293, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9119396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9119396</a>] [<a href="https://doi.org/10.1006/geno.1996.4584" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9119396">Miyake et al. (1997)</a> described YAC and cosmid contigs encompassing the FCMD candidate region on 9q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9119396+8940277+7546737" 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>FCMD is characterized clinically by a peak motor function that, at best, usually allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the ability to walk unassisted. Looking for genetic heterogeneity in FCMD, <a href="#13" class="mim-tip-reference" title="Kondo-Iida, E., Saito, K., Tanaka, H., Tsuji, S., Ishihara, T., Osawa, M., Fukuyama, Y., Toda, T. <strong>Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.</strong> Hum. Genet. 99: 427-432, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099829</a>] [<a href="https://doi.org/10.1007/s004390050384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9099829">Kondo-Iida et al. (1997)</a> performed linkage analysis in 10 families with ambulant cases using DNA markers flanking the FCMD locus. Linkage and linkage disequilibrium were found, suggesting homogeneity. The authors further conducted haplotype analysis in a family in which 1 sib was ambulant, whereas the other was not. They found that the sibs had the same haplotype at 9 marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, <a href="#13" class="mim-tip-reference" title="Kondo-Iida, E., Saito, K., Tanaka, H., Tsuji, S., Ishihara, T., Osawa, M., Fukuyama, Y., Toda, T. <strong>Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.</strong> Hum. Genet. 99: 427-432, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099829</a>] [<a href="https://doi.org/10.1007/s004390050384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9099829">Kondo-Iida et al. (1997)</a> concluded that, genetically, ambulant cases are part of the FCMD spectrum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9099829" 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> described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. They reported that there is a retrotransposal insertion (<a href="/entry/607440#0001">607440.0001</a>) of tandemly repeated sequences in the FKTN gene in all FCMD chromosomes carrying the founder haplotype (87%). The authors stated that FCMD is the first human disease known to be caused by an ancient retrotransposal integration. Two independent point mutations (<a href="/entry/607440#0002">607440.0002</a> and <a href="/entry/607440#0003">607440.0003</a>) in patients with FCMD confirmed that mutation in this gene is responsible for FCMD. <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><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> performed a systematic analysis of the FKTN gene in 107 unrelated patients and identified 4 novel nonfounder mutations in 5 of them: 1 missense, 1 nonsense, 1 L1 insertion (<a href="/entry/607440#0004">607440.0004</a>), and one 1-bp insertion (<a href="/entry/607440#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><a href="#24" 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 truncating mutation in the FKTN gene (<a href="/entry/607440#0006">607440.0006</a>) in a Turkish patient with WWS. The first-cousin parents and an unaffected brother were heterozygous for the mutation. 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 FCMD due to the mutation in the FKTN gene, the authors noted that classification of the disease in this patient could be difficult because the phenotype was slightly different and more closely resembled 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><p>In a Turkish patient with WWS, <a href="#3" 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 nonsense mutation in the FKTN gene (<a href="/entry/607440#0007">607440.0007</a>). The authors noted that the phenotype in this patient was more consistent with WWS than with FCMD, 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><p>In a Spanish infant 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 compound heterozygosity for 2 mutations in the FKTN gene (<a href="/entry/607440#0012">607440.0012</a> and <a href="/entry/607440#0013">607440.0013</a>). 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 a 1-bp insertion in the FKTN gene (<a href="/entry/607440#0005">607440.0005</a>) that had previously been identified in compound heterozygosity in patients with FCMD and a less severe form of muscular dystrophy (<a href="/entry/611588">611588</a>). The son was homozygous for the insertion, and the unaffected parents were heterozygous carriers. <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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<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="/entry/607440#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. Their results provided strong evidence that loss of function of fukutin is the major cause of FCMD, and appeared to shed some light on the mechanism responsible for the broad clinical spectrum seen in this disorder. <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>To establish a genotype-phenotype correlation, <a href="#23" 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 having 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 severely affected patients 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="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><p><a href="#23" 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="#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 the retroposon sequence insertion (<a href="/entry/607440#0001">607440.0001</a>) was found in 125 (87%) of 144 FCMD chromosomes, whereas it was found in only 1 of 176 chromosomes in unrelated normal individuals; the frequency of 1 in 88 individuals corresponded well to that of FCMD carriers in the Japanese population. <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><a href="#35" 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> developed a rapid PCR-based diagnostic method for detecting the FCMD retroposon insertion mutation using 3 primers simultaneously. 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 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>
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<p><a href="#25" class="mim-tip-reference" title="Takada, K., Nakamura, H., Tanaka, J. <strong>Cortical dysplasia in congenital muscular dystrophy with central nervous system involvement (Fukuyama type).</strong> J. Neuropath. Exp. Neurol. 43: 395-407, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6737009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6737009</a>] [<a href="https://doi.org/10.1097/00005072-198407000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6737009">Takada et al. (1984)</a> rejected the suggestion that the myopathy is secondary to the CNS changes for several reasons, including the finding that the morphologic changes are dystrophic in nature. They postulated a pleiotropic gene accounting for the lesions in both skeletal muscles and the nervous system. As reviewed by <a href="#2" class="mim-tip-reference" title="Beggs, A. H., Neumann, P. E., Arahata, K., Arikawa, E., Nonaka, I., Anderson, M. S., Kunkel, L. M. <strong>Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.</strong> Proc. Nat. Acad. Sci. 89: 623-627, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1731332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1731332</a>] [<a href="https://doi.org/10.1073/pnas.89.2.623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1731332">Beggs et al. (1992)</a>, a few patients with the clinical diagnosis of FCMD have been shown to have abnormalities of dystrophin (<a href="/entry/300377">300377</a>) on skeletal muscle biopsy. Epidemiologic data suggested that only 1 in about 3,500 males with autosomal recessive FCMD should have abnormal dystrophin; however, abnormal dystrophin was observed in 3 of 23 FCMD males. As an explanation, <a href="#2" class="mim-tip-reference" title="Beggs, A. H., Neumann, P. E., Arahata, K., Arikawa, E., Nonaka, I., Anderson, M. S., Kunkel, L. M. <strong>Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.</strong> Proc. Nat. Acad. Sci. 89: 623-627, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1731332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1731332</a>] [<a href="https://doi.org/10.1073/pnas.89.2.623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1731332">Beggs et al. (1992)</a> suggested that dystrophin and the FCMD gene product interact and that the early onset and greater severity of the phenotype in these patients, relative to Duchenne muscular dystrophy, was due to their being heterozygous for the FCMD mutation in addition to being hemizygous for DMD. This combined genotype was predicted to occur in 1 in about 175,000 Japanese males. The model might explain some of the clinical and pathologic variability seen in FCMD and could have potential implications for understanding the inheritance of other autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products. The sex ratio in such instances might display a deviation from 1:1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1731332+6737009" 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="#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> could not demonstrate fukutin in skeletal muscle using polyclonal and monoclonal antibodies. In transfected COS-7 cells, they found evidence of colocalization 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 major manifestation of FCMD is micropolygyria (type II lissencephaly), in which neuronal lamination of normal 6-layered cortex is lacking because of a defect in the migration of neurons. Other genes implicated in cortical dysgenesis disorders that appear to function in the migration and assembly of neurons during cortical histogenesis include DCX (<a href="/entry/300121">300121</a>), LIS1 (<a href="/entry/601545">601545</a>), and RELN (<a href="/entry/600514">600514</a>). <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><a href="#14" class="mim-tip-reference" title="Matsumura, K., Nonaka, I., Campbell, K. P. <strong>Abnormal expression of dystrophin-associated proteins in Fukuyama-type congenital muscular dystrophy.</strong> Lancet 341: 521-522, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8094772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8094772</a>] [<a href="https://doi.org/10.1016/0140-6736(93)90279-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8094772">Matsumura et al. (1993)</a> reported that dystrophin-associated proteins such as alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) have abnormally low expression in FCMD. DAG1 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="#9" 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 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="#9" 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="#15" class="mim-tip-reference" title="Michele, D. E., Barresi, R., Kanagawa, M., Saito, F., Cohn, R. D., Satz, J. S., Dollar, J., Nishino, I., Kelley, R. I., Somer, H., Straub, V., Mathews, K. D., Moore, S. A., Campbell, K. P. <strong>Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies.</strong> Nature 418: 417-422, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12140558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12140558</a>] [<a href="https://doi.org/10.1038/nature00837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12140558">Michele et al. (2002)</a> demonstrated in both MEB disease and FCMD patients that alpha-dystroglycan is expressed at the muscle membrane, but similar hypoglycosylation in the diseases directly abolishes binding activity of dystroglycan for the ligands laminin (see <a href="/entry/156225">156225</a>), neurexin (see <a href="/entry/600565">600565</a>), and agrin (<a href="/entry/103320">103320</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8094772+12140558+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><a href="#27" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Sese, J., Okinaga, T., Tsukahara, T., Guicheney, P., Ozono, K., Nishino, I., Morishita, S., Toda, T. <strong>Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha-2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?</strong> Biochem. Biophys. Res. Commun. 342: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16487936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16487936</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.12.224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16487936">Taniguchi et al. (2006)</a> performed histologic examination and cDNA microarray analysis of skeletal muscle biopsy specimens from 4 patients with FCMD and 1 with MDC1A (<a href="/entry/607855">607855</a>) at various ages during childhood. Histologic examination showed dystrophic features, fiber size variation, prominent interstitial tissue, and adipose tissue proliferation. Inflammation, necrosis, and regeneration of muscle fibers were less apparent, especially compared to biopsies from patients with DMD. FCMD and MDC1A samples showed increased expression of extracellular matrix genes, such as COL3A1 (<a href="/entry/120180">120180</a>), THBS4 (<a href="/entry/600715">600715</a>), and OSF2 (POSTN; <a href="/entry/608777">608777</a>), whereas there was downregulation of genes encoding mature muscle components, including MYH7 (<a href="/entry/160760">160760</a>), TCAP (<a href="/entry/604488">604488</a>), DES (<a href="/entry/125660">125660</a>), and MYH1 (<a href="/entry/160730">160730</a>). Upregulation of gene expression occurred predominantly in muscle fibers and only slightly in fibroblasts. In contrast, a previous microarray analysis of DMD muscle (<a href="#21" class="mim-tip-reference" title="Noguchi, S., Tsukahara, T., Fujita, M., Kurokawa, R., Tachikawa, M., Toda, T., Tsujimoto, A., Arahata, K., Nishino, I. <strong>cDNA microarray analysis of individual Duchenne muscular dystrophy patients.</strong> Hum. Molec. Genet. 12: 595-600, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12620965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12620965</a>]" pmid="12620965">Noguchi et al., 2003</a>) reported upregulation of genes encoding muscle components, reflecting enhanced active muscle fiber regeneration following degeneration in DMD. <a href="#27" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Sese, J., Okinaga, T., Tsukahara, T., Guicheney, P., Ozono, K., Nishino, I., Morishita, S., Toda, T. <strong>Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha-2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?</strong> Biochem. Biophys. Res. Commun. 342: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16487936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16487936</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.12.224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16487936">Taniguchi et al. (2006)</a> suggested that the primary pathologic feature of FCMD and MDC1A is interstitial fibrosis without muscle degeneration and regeneration, which distinguishes these disorders from DMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12620965+16487936" 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 gene expression profiling of skeletal muscle from patients with FCMD, <a href="#26" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Fukudome, T., Okinaga, T., Tsukahara, T., Tajima, Y., Ozono, K., Nishino, I., Nonaka, I., Toda, T. <strong>Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in alpha-dystroglycanopathies.</strong> Hum. Molec. Genet. 15: 1279-1289, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16531417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16531417</a>] [<a href="https://doi.org/10.1093/hmg/ddl045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16531417">Taniguchi et al. (2006)</a> found a pattern suggesting maturational arrest of muscle fibers, with a decrease in developmentally regulated genes, such as the mature myosin heavy chain components MYH1 (<a href="/entry/160730">160730</a>), MYH2 (<a href="/entry/160740">160740</a>), and MYH7, and myogenic factors MRF4 (<a href="/entry/159991">159991</a>) and MYOD1 (<a href="/entry/159970">159970</a>), as well as upregulated MYOG (<a href="/entry/159980">159980</a>). RT-PCR analysis showed upregulation of the fetal cholinergic receptor isoform CHRNG (<a href="/entry/100730">100730</a>). Histologic studies showed an increase in type 2C muscle fibers, which are mainly seen in fetal muscle or regenerating fibers. The results indicated an unbalanced differentiation process. Histologic and electron microscopic analysis of FCMD samples showed aberrant neuromuscular junctions (NMJs), with fewer synaptic folds and secondary clefts than normal, also consistent with maturational arrest. These NMJs also showed functional impairment. Importantly, these changes were also different from that observed in DMD. Overall, the findings suggested that FCMD is not a classic muscular dystrophy, but rather is also characterized by an arrest of development and differentiation of both muscle fibers and the NMJ. <a href="#26" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Fukudome, T., Okinaga, T., Tsukahara, T., Tajima, Y., Ozono, K., Nishino, I., Nonaka, I., Toda, T. <strong>Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in alpha-dystroglycanopathies.</strong> Hum. Molec. Genet. 15: 1279-1289, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16531417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16531417</a>] [<a href="https://doi.org/10.1093/hmg/ddl045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16531417">Taniguchi et al. (2006)</a> hypothesized that hypoglycosylated DAG1 interferes with proper DAG1 aggregation in critical regions during muscle development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16531417" 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="#28" 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. 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 in model mice, rescuing normal fukutin mRNA expression and protein production. Antisense oligonucleotide treatment also restored fukutin functions, including O-glycosylation of alpha-dystroglycan and laminin binding by alpha-dystroglycan. Moreover, <a href="#28" 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="#28" 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 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>
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<p><a href="#15" class="mim-tip-reference" title="Michele, D. E., Barresi, R., Kanagawa, M., Saito, F., Cohn, R. D., Satz, J. S., Dollar, J., Nishino, I., Kelley, R. I., Somer, H., Straub, V., Mathews, K. D., Moore, S. A., Campbell, K. P. <strong>Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies.</strong> Nature 418: 417-422, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12140558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12140558</a>] [<a href="https://doi.org/10.1038/nature00837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12140558">Michele et al. (2002)</a> showed that the posttranslational biochemical and functional disruption of alpha-dystroglycan in humans is recapitulated in the muscle and central nervous system of mutant myodystrophy (myd) mice, which have a mutation in the Large gene (<a href="/entry/603590">603590</a>). They demonstrated that myd mice have abnormal neuronal migration in the cerebral cortex, cerebellum, and hippocampus, and show disruption of the basal lamina. In addition, dystroglycan in myd mice targets proteins to functional sites in brain through its interactions with extracellular matrix proteins. <a href="#15" class="mim-tip-reference" title="Michele, D. E., Barresi, R., Kanagawa, M., Saito, F., Cohn, R. D., Satz, J. S., Dollar, J., Nishino, I., Kelley, R. I., Somer, H., Straub, V., Mathews, K. D., Moore, S. A., Campbell, K. P. <strong>Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies.</strong> Nature 418: 417-422, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12140558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12140558</a>] [<a href="https://doi.org/10.1038/nature00837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12140558">Michele et al. (2002)</a> suggested that at least 3 mammalian genes function within a convergent posttranslational processing pathway during the biosynthesis of dystroglycan and that abnormal dystroglycan-ligand interactions underlie the pathogenic mechanism of muscular dystrophy with brain abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12140558" 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="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.-I., 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 (see <a href="/entry/156225">156225</a>)-binding levels to be 50% of normal. In contrast, intact alpha-dystroglycan was undetectable in the dystrophic Large(myd) mouse, 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="#10" 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.-I., 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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<a href="#Murakami1975" class="mim-tip-reference" title="Murakami, T., Konishi, Y., Takamiya, M., Tsukagoshi, H. <strong>Congenital muscular dystrophy associated with micropolygyria--report of 2 cases.</strong> Acta Path. Jpn. 25: 599-612, 1975.">Murakami et al. (1975)</a>
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddn387" target="_blank">Full Text</a>]
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<strong>Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle , at the neuromuscular junction, and after injury.</strong>
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Neuron 15: 573-584, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7546737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7546737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7546737" 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/10.1016/0896-6273(95)90146-9" target="_blank">Full Text</a>]
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<a id="34" 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.
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<strong>Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.</strong>
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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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<a id="35" 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.
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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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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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<a id="36" 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.
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<strong>Fukutin gene retrotransposal insertion in a non-Japanese Fukuyama congenital muscular dystrophy (FCMD) patient.</strong>
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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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<a id="37" class="mim-anchor"></a>
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<a id="Yoshioka1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yoshioka, M., Kuroki, S.
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<strong>Clinical spectrum and genetic studies of Fukuyama congenital muscular dystrophy.</strong>
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Am. J. Med. Genet. 53: 245-250, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7856660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7856660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7856660" 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.1320530309" target="_blank">Full Text</a>]
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<br />
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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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Ada Hamosh - updated : 1/10/2012
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/10/2011<br>Cassandra L. Kniffin - updated : 11/17/2010<br>Cassandra L. Kniffin - updated : 12/4/2009<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 7/12/2006<br>Cassandra L. Kniffin - updated : 3/9/2006<br>Cassandra L. Kniffin - updated : 5/7/2003<br>Victor A. McKusick - updated : 12/23/2002<br>Ada Hamosh - updated : 9/11/2002<br>George E. Tiller - updated : 3/5/2001<br>Victor A. McKusick - updated : 12/18/2000<br>Victor A. McKusick - updated : 5/22/2000<br>Victor A. McKusick - updated : 11/19/1999<br>Victor A. McKusick - updated : 8/12/1998<br>Victor A. McKusick - updated : 5/16/1997<br>Victor A. McKusick - updated : 3/16/1997<br>Moyra Smith - updated : 1/31/1997<br>Orest Hurko - updated : 9/27/1995
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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carol : 12/14/2021
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<span class="mim-text-font">
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carol : 08/19/2016<br>mcolton : 11/11/2014<br>carol : 10/7/2014<br>mcolton : 10/6/2014<br>mcolton : 10/2/2014<br>alopez : 1/10/2012<br>terry : 1/10/2012<br>terry : 9/28/2011<br>wwang : 4/14/2011<br>ckniffin : 2/10/2011<br>wwang : 11/24/2010<br>ckniffin : 11/17/2010<br>carol : 11/10/2010<br>ckniffin : 11/8/2010<br>ckniffin : 12/8/2009<br>ckniffin : 12/4/2009<br>wwang : 11/13/2009<br>ckniffin : 10/27/2009<br>wwang : 8/20/2009<br>wwang : 11/26/2007<br>wwang : 8/3/2006<br>ckniffin : 7/12/2006<br>wwang : 3/17/2006<br>ckniffin : 3/9/2006<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<br>terry : 12/23/2002<br>carol : 10/18/2002<br>ckniffin : 10/15/2002<br>alopez : 9/13/2002<br>carol : 9/11/2002<br>cwells : 3/13/2002<br>cwells : 3/6/2001<br>cwells : 3/5/2001<br>cwells : 3/5/2001<br>mcapotos : 1/18/2001<br>mcapotos : 1/5/2001<br>terry : 12/18/2000<br>mcapotos : 6/12/2000<br>mcapotos : 6/9/2000<br>terry : 5/22/2000<br>alopez : 12/2/1999<br>terry : 11/19/1999<br>carol : 8/12/1998<br>terry : 8/12/1998<br>mark : 5/19/1997<br>terry : 5/16/1997<br>mark : 3/16/1997<br>terry : 3/10/1997<br>jamie : 2/4/1997<br>mark : 1/31/1997<br>jamie : 1/17/1997<br>mimman : 2/8/1996<br>terry : 6/20/1995<br>carol : 2/21/1995<br>davew : 7/6/1994<br>carol : 12/2/1993<br>carol : 3/17/1993
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<span class="mim-font">
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<strong>#</strong> 253800
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<h3>
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<span class="mim-font">
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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY; FCMD<br />
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WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, FKTN-RELATED
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<strong>SNOMEDCT:</strong> 111502003;
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<strong>ORPHA:</strong> 272, 588, 899;
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<strong>DO:</strong> 0050559;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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<th>
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Phenotype
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<th>
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Phenotype <br /> MIM number
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Inheritance
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<th>
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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9q31.2
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<span class="mim-font">
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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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253800
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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FKTN
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</td>
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<td>
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<span class="mim-font">
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607440
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<span class="mim-font">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A4; MDDGA4), previously designated Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), or muscle-eye-brain disease (MEB), is caused by homozygous or compound heterozygous mutation in the gene encoding fukutin (FKTN; 607440) on chromosome 9q31.</p><p>Mutation in the FKTN gene can also cause a less severe congenital muscular dystrophy-dystroglycanopathy without impaired intellectual development (type B4; MDDGB4; 613152) and a limb-girdle muscular dystrophy-dystroglycanopathy (type C4; MDDGC4; 611588).</p>
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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 class="mim-text-font">
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<p>MDDGA4 is a severe autosomal recessive muscular dystrophy-dystroglycanopathy with characteristic brain and eye malformations, seizures, and mental retardation. Cardiac involvement in FCMD/MEB occurs in the second decade of life in those who survive. FKTN-related Walker-Warburg syndrome is a more severe manifestation of the disorder, with death usually in the first year of life. These entities are part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007; Muntoni and Voit, 2004; Muntoni et al., 2008). </p><p>For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).</p>
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<div>
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<br />
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<span class="mim-text-font">
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<p>This disorder has been described as FCMD/muscle-eye-brain disease (MEB) and the more severe Walker-Warburg syndrome; these designations have been retained here when used in the literature.</p><p><strong><em>Fukuyama Congenital Muscular Dystrophy/FKTN-Related Muscle-Eye-Brain Disease</em></strong></p><p>
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Fukuyama et al. (1960) described a novel form of congenital muscular dystrophy. Parental consanguinity was present in 6 families; in 2 sibships, multiple cases were observed. Fukuyama et al. (1981) stated that more than 200 cases had been recognized clinically in Japan. Patients manifest generalized muscle weakness and hypotonia from early infancy and most are unable to walk without support. All are mentally retarded and some have seizures, abnormal electroencephalograms, and abnormal CT scans. The brain malformations in FCMD include cerebral and cerebellar micropolygyria, fibroglial proliferation of the leptomeninges, hydrocephalus, focal interhemispheric fusion, and hypoplasia of the corticospinal tracts. </p><p>Histologic changes in skeletal muscle were similar to those of Duchenne muscular dystrophy (DMD; 310200) (Nonaka et al., 1982). Caucasian patients were studied by Dambska et al. (1982). Miura and Shirasawa (1987) described severe myocardial fibrosis in the autopsy of a 17-year-old Japanese male. Aida et al. (1994) demonstrated cerebellar polymicrogyria and the presence of cerebellar cysts related to the polymicrogyria in 23 of 25 patients with congenital muscular dystrophy. These 2 changes on MRI are distinctive enough to suggest the radiologic diagnosis of this disorder. </p><p>Yoshioka and Kuroki (1994) performed clinical and genetic studies in 41 families with FCMD in Japan in an attempt to distinguish it from the Walker-Warburg syndrome and muscle-eye-brain disease, both of which, like FCMD, show an association of type II lissencephaly and ocular anomalies. Two or more children were affected in 9 families. Parental consanguinity was documented in 5 of the 32 sporadic cases and in none of the familial cases. In evaluations of 7 sib pairs, a difference between sibs in motor ability was apparent in 4. Mental status also showed wide variation. The EEG findings differed in 2 of 7 sib pairs. The familial FCMD patients showed relatively more severe motor disability than that in the sporadic FCMD patients, whereas the status in regard to mental function and convulsions showed no significant difference in the 2 groups. In 1 family, hydrocephalus was found in only 1 of the sibs; in addition, this patient showed encephalocele and retinal detachment at birth. Yoshioka and Kuroki (1994) emphasized the broad clinical spectrum of FCMD and the phenotypic overlap with mild WWS and MEB disease. </p><p>Toda et al. (1995) used polymorphic microsatellites flanking the FCMD locus on 9q31-q33 (see MAPPING) to study a family in which 3 sibs were affected with either FCMD or WWS. One sib was labeled as FCMD because he showed severe hypotonia with dystrophic findings on a muscle biopsy, in addition to pachygyria on computed tomographic scan. At age 3 years, the patient developed retinal detachment in both eyes. The second pregnancy resulted in a male infant with anencephaly who survived for 5 minutes. At birth, the third sib exhibited pachygyria, cephalocele, hydrocephalus, bilateral retinal detachment, elevated serum creatine kinase, and arthrogryposis multiplex congenita, all features consistent with Walker-Warburg syndrome. Haplotype analysis demonstrated identity of each allele in the 2 surviving sibs. The parents were nonconsanguineous, and the disease-related haplotypes were different on the 2 alleles of the patients. Toda et al. (1995) presented this as evidence that the 2 disorders may be allelic. </p><p>Godfrey et al. (2007) identified 1 patient with FKTN-related FCMD/MEB among a larger study of 92 probands with muscular dystrophy and evidence of a dystroglycanopathy. Although clinical details were limited, the patient had infantile onset, muscle hypertrophy, increased serum creatine kinase, and low IQ. He only achieved sitting. There were no eye abnormalities, but brain MRI showed cerebellar cysts, white matter abnormalities, and hydrocephalus. As part of the larger study, Godfrey et al. (2007) defined FCMD/MEB as congenital onset of muscular dystrophy with fronto-parietal pachygyria, cerebellar dysplasia, and frequent flattening of the pons and brainstem. Eye abnormalities are often seen, and rare patients may acquire the ability to walk or learn a few words. </p><p>Vuillaumier-Barrot et al. (2009) reported 2 Portuguese sisters with mental retardation and muscular dystrophy associated with compound heterozygous mutations in the FKTN gene (A170E, 607440.0016; Y371C, 607440.0017). Both had congenital hip dislocation, congenital hypotonia, and delayed motor development. Muscle weakness was diffuse and progressive with axial and proximal limb predominance and moderate facial involvement; both had significantly increased serum creatine kinase. One sister lost the ability to walk in the first decade of life and developed multiple contractures and severe respiratory insufficiency. She was mentally retarded and had epileptic seizures from age 13 years. The other sister had knee contractures from the first year of life, spinal rigidity, and scoliosis. She developed severe and progressive restrictive respiratory insufficiency and nondilated left ventricular dysfunction in her teens. At age 19 years, she had diffuse amyotrophy, severe multiple joint contractures, and a stiff hyperextended neck. Both were mentally retarded, but 1 had significantly better verbal abilities. Brain MRI showed brainstem atrophy, marked cerebellar vermis hypoplasia and cysts, and cortical brain atrophy. One patient had cerebellar polymicrogyria. Vuillaumier-Barrot et al. (2009) commented that few patients outside of Japan had been reported with this disorder. </p><p>Tunc et al. (2009) reported a female infant with FCMD, born of consanguineous Turkish parents, who had severe hypotonia and abnormal limb movements. Just after birth, she showed rhythmic and jerky movements of all 4 limbs, both spontaneously and in response to stimulus, but these were associated with a normal EEG. The findings were consistent with hyperekplexia (see HKPX1, 149400). Brain imaging showed absent corpus callosum, lissencephaly, pachygyria, ventricular dilatation, subcortical white matter abnormalities, and brainstem and cerebellar hypoplasia. She died at day 15. </p><p>Xiong et al. (2009) reported a Chinese boy with FCMD. He showed hypotonia from birth, achieved head control at age 2 years, and sat unsupported at age 4 years, but was unable to slide on his buttocks. He developed progressive knee and ankle contractures after age 1 year. He had facial muscle and generalized muscle weakness with severe muscle atrophy, but hypertrophy of the calf muscle. Brain MRI showed patchy periventricular hyperintensities, frontal lobe polymicrogyria, cerebellar cysts, and cerebellar and brainstem hypoplasia. He had an IQ of 52 and spoke only a few words. Muscle biopsy showed prominent dystrophic features and decreased alpha-dystroglycan staining. Genetic analysis identified compound heterozygosity for 2 mutations in the fukutin gene: the common Japanese founder allele (607440.0001) 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>FKTN-Related Walker-Warburg Syndrome</em></strong></p><p>
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Silan et al. (2003) reported a Turkish patient with a severe congenital muscular dystrophy phenotype most closely resembling Walker-Warburg syndrome. 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. </p><p>Beltran-Valero de Bernabe et al. (2003) reported a Turkish patient with Walker-Warburg syndrome. Born to second-degree consanguineous parents, the patient had macrocephaly, anterior chamber abnormalities, severe hypotonia, and severe brain malformations, including hydrocephalus, agyria/pachygyria, absent corpus callosum and cerebellar vermis, and white matter hyperlucencies. The patient died at 4.5 months of age. </p><p>Godfrey et al. (2007) identified 1 patient with FKTN-related WWS among a larger study of 92 probands with muscular dystrophy and evidence of 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. As part of the larger study, Godfrey et al. (2007) defined WWS as prenatal onset or onset of birth of absence of motor development and severe structural brain abnormalities, including complete agyria or severe lissencephaly, marked hydrocephalus, severe cerebellar involvement, and complete or partial absence of the corpus callosum. Common eye abnormalities included congenital cataracts, microphthalmia, and buphthalmos. Death usually occurred before 1 year of age. Genetic analysis identified a homozygous truncating mutation in the FKTN gene (R307X; 607440.0018). </p><p>Cotarelo et al. (2008) described a Spanish female infant, born of nonconsanguineous parents, who was diagnosed with Walker-Warburg syndrome and died on day 5 of life after suffering respiratory apnea and bradycardia. She had a dysmorphic face with low-set malformed ears, left preauricular tag, thoracic hemivertebrae, and cardiac defects. Brain CT scan showed overriding cranial bones, severe left microphthalmia, monolobar holoprosencephaly, and internal and external hydrocephalus. Cortex and white matter could not be differentiated, and no details could be observed in the posterior fossa. At autopsy, the medial aspect of the brain showed an interhemispheric cyst, incomplete cleavage of the thalamus and corpora quadrigemina, an absent corpus callosum, and rhombencephalic hypoplasia. Punctate hemorrhages were seen in the parenchyma, and ventriculitis was identified. An atrial septal defect (foramen ovale), double subaortic ventricular defect, hypoplastic left ventricle outlet, stenotic pulmonary valve, and infundibular transposition of the great vessels with no innominate vein were also found. The eyes were malformed and exhibited retinal dysplasia. </p>
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<strong>Inheritance</strong>
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<p>The involvement of multiple sibs of both sexes and parental consanguinity reported by Fukuyama et al. (1960) supported autosomal recessive inheritance.</p>
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<strong>Mapping</strong>
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<p>Toda et al. (1993) performed genetic linkage analysis with polymorphic microsatellite markers in 21 FCMD families, 13 of which had consanguineous marriages. Significant lod scores were found with 3 loci on 9q31-q33. Multipoint analysis placed the FCMD gene in the interval between D9S58 and D9S59, with a maximum location score of 39.0. Homozygosity mapping supported the assignment. In a nonconsanguineous sibship in which 1 sib was thought to have FCMD and another sib was thought to have WWS, Toda et al. (1995) found linkage to the FCMD locus on chromosome 9q31-q33, suggesting that they may be allelic disorders, or at least caused by the same gene in this family. </p><p>Toda et al. (1996) refined the map location of FCMD to a 5-cM region between D9S127 and D9S2111. They reported that there is linkage disequilibrium between FCMD and markers in 9q31. Haplotype analysis using the markers D9S2105, D9S2107, and D9S172 indicated that most FCMD-bearing chromosomes in Japanese pedigrees were derived from a single ancestral founder. On the basis of haplotype analysis, Toda et al. (1996) concluded that the FCMD gene most likely lies on 9q31 within a less than 100-kb region containing the D9S2107 marker. They suggested that the muscle-specific receptor tyrosine kinase gene (MUSK; 601296) reported by Valenzuela et al. (1995) is a candidate FCMD gene since its map location overlaps with that of FCMD. Miyake et al. (1997) described YAC and cosmid contigs encompassing the FCMD candidate region on 9q31. </p><p>FCMD is characterized clinically by a peak motor function that, at best, usually allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the ability to walk unassisted. Looking for genetic heterogeneity in FCMD, Kondo-Iida et al. (1997) performed linkage analysis in 10 families with ambulant cases using DNA markers flanking the FCMD locus. Linkage and linkage disequilibrium were found, suggesting homogeneity. The authors further conducted haplotype analysis in a family in which 1 sib was ambulant, whereas the other was not. They found that the sibs had the same haplotype at 9 marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, Kondo-Iida et al. (1997) concluded that, genetically, ambulant cases are part of the FCMD spectrum. </p>
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<strong>Molecular Genetics</strong>
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<p>Kobayashi et al. (1998) described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. They reported that there is a retrotransposal insertion (607440.0001) of tandemly repeated sequences in the FKTN gene in all FCMD chromosomes carrying the founder haplotype (87%). The authors stated that FCMD is the first human disease known to be caused by an ancient retrotransposal integration. Two independent point mutations (607440.0002 and 607440.0003) in patients with FCMD confirmed that mutation in this gene is responsible for FCMD. </p><p>Kondo-Iida et al. (1999) performed a systematic analysis of the FKTN gene in 107 unrelated patients and identified 4 novel nonfounder mutations in 5 of them: 1 missense, 1 nonsense, 1 L1 insertion (607440.0004), and one 1-bp insertion (607440.0005). </p><p>Silan et al. (2003) identified a homozygous truncating mutation in the FKTN gene (607440.0006) in a Turkish patient with WWS. The first-cousin parents and an unaffected brother were heterozygous for the mutation. 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 FCMD due to the mutation in the FKTN gene, the authors noted that classification of the disease in this patient could be difficult because the phenotype was slightly different and more closely resembled Walker-Warburg syndrome. </p><p>In a Turkish patient with WWS, Beltran-Valero de Bernabe et al. (2003) identified a homozygous nonsense mutation in the FKTN gene (607440.0007). The authors noted that the phenotype in this patient was more consistent with WWS than with FCMD, and established a genotype/phenotype correlation for fukutin mutations that cause complete loss of protein function. </p><p>In a Spanish infant with WWS, Cotarelo et al. (2008) identified compound heterozygosity for 2 mutations in the FKTN gene (607440.0012 and 607440.0013). In cell lines from unrelated Ashkenazi Jewish parents and their son, who was diagnosed with WWS, Cotarelo et al. (2008) identified a 1-bp insertion in the FKTN gene (607440.0005) that had previously been identified in compound heterozygosity in patients with FCMD and a less severe form of muscular dystrophy (611588). The son was homozygous for the insertion, and the unaffected parents were heterozygous carriers. </p>
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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. Their results provided strong evidence that loss of function of fukutin is the major cause of FCMD, and appeared to shed some light on the mechanism responsible for the broad clinical spectrum seen in this disorder. </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 having 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 severely affected patients 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. </p><p>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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<p>Kobayashi et al. (1998) reported that the retroposon sequence insertion (607440.0001) was found in 125 (87%) of 144 FCMD chromosomes, whereas it was found in only 1 of 176 chromosomes in unrelated normal individuals; the frequency of 1 in 88 individuals corresponded well to that of FCMD carriers in the Japanese population. </p><p>Watanabe et al. (2005) developed a rapid PCR-based diagnostic method for detecting the FCMD retroposon insertion mutation using 3 primers simultaneously. 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 Japan. </p>
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<p>Takada et al. (1984) rejected the suggestion that the myopathy is secondary to the CNS changes for several reasons, including the finding that the morphologic changes are dystrophic in nature. They postulated a pleiotropic gene accounting for the lesions in both skeletal muscles and the nervous system. As reviewed by Beggs et al. (1992), a few patients with the clinical diagnosis of FCMD have been shown to have abnormalities of dystrophin (300377) on skeletal muscle biopsy. Epidemiologic data suggested that only 1 in about 3,500 males with autosomal recessive FCMD should have abnormal dystrophin; however, abnormal dystrophin was observed in 3 of 23 FCMD males. As an explanation, Beggs et al. (1992) suggested that dystrophin and the FCMD gene product interact and that the early onset and greater severity of the phenotype in these patients, relative to Duchenne muscular dystrophy, was due to their being heterozygous for the FCMD mutation in addition to being hemizygous for DMD. This combined genotype was predicted to occur in 1 in about 175,000 Japanese males. The model might explain some of the clinical and pathologic variability seen in FCMD and could have potential implications for understanding the inheritance of other autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products. The sex ratio in such instances might display a deviation from 1:1. </p><p>Kobayashi et al. (1998) could not demonstrate fukutin in skeletal muscle using polyclonal and monoclonal antibodies. In transfected COS-7 cells, they found evidence of colocalization 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. A major manifestation of FCMD is micropolygyria (type II lissencephaly), in which neuronal lamination of normal 6-layered cortex is lacking because of a defect in the migration of neurons. Other genes implicated in cortical dysgenesis disorders that appear to function in the migration and assembly of neurons during cortical histogenesis include DCX (300121), LIS1 (601545), and RELN (600514). </p><p>Matsumura et al. (1993) reported that dystrophin-associated proteins such as alpha-dystroglycan (DAG1; 128239) have abnormally low expression in FCMD. DAG1 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 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. Michele et al. (2002) demonstrated in both MEB disease and FCMD patients that alpha-dystroglycan is expressed at the muscle membrane, but similar hypoglycosylation in the diseases directly abolishes binding activity of dystroglycan for the ligands laminin (see 156225), neurexin (see 600565), and agrin (103320). </p><p>Taniguchi et al. (2006) performed histologic examination and cDNA microarray analysis of skeletal muscle biopsy specimens from 4 patients with FCMD and 1 with MDC1A (607855) at various ages during childhood. Histologic examination showed dystrophic features, fiber size variation, prominent interstitial tissue, and adipose tissue proliferation. Inflammation, necrosis, and regeneration of muscle fibers were less apparent, especially compared to biopsies from patients with DMD. FCMD and MDC1A samples showed increased expression of extracellular matrix genes, such as COL3A1 (120180), THBS4 (600715), and OSF2 (POSTN; 608777), whereas there was downregulation of genes encoding mature muscle components, including MYH7 (160760), TCAP (604488), DES (125660), and MYH1 (160730). Upregulation of gene expression occurred predominantly in muscle fibers and only slightly in fibroblasts. In contrast, a previous microarray analysis of DMD muscle (Noguchi et al., 2003) reported upregulation of genes encoding muscle components, reflecting enhanced active muscle fiber regeneration following degeneration in DMD. Taniguchi et al. (2006) suggested that the primary pathologic feature of FCMD and MDC1A is interstitial fibrosis without muscle degeneration and regeneration, which distinguishes these disorders from DMD. </p><p>By gene expression profiling of skeletal muscle from patients with FCMD, Taniguchi et al. (2006) found a pattern suggesting maturational arrest of muscle fibers, with a decrease in developmentally regulated genes, such as the mature myosin heavy chain components MYH1 (160730), MYH2 (160740), and MYH7, and myogenic factors MRF4 (159991) and MYOD1 (159970), as well as upregulated MYOG (159980). RT-PCR analysis showed upregulation of the fetal cholinergic receptor isoform CHRNG (100730). Histologic studies showed an increase in type 2C muscle fibers, which are mainly seen in fetal muscle or regenerating fibers. The results indicated an unbalanced differentiation process. Histologic and electron microscopic analysis of FCMD samples showed aberrant neuromuscular junctions (NMJs), with fewer synaptic folds and secondary clefts than normal, also consistent with maturational arrest. These NMJs also showed functional impairment. Importantly, these changes were also different from that observed in DMD. Overall, the findings suggested that FCMD is not a classic muscular dystrophy, but rather is also characterized by an arrest of development and differentiation of both muscle fibers and the NMJ. Taniguchi et al. (2006) hypothesized that hypoglycosylated DAG1 interferes with proper DAG1 aggregation in critical regions during muscle development. </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. 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 in model mice, rescuing normal fukutin mRNA expression and protein production. Antisense oligonucleotide treatment also restored fukutin functions, including O-glycosylation of alpha-dystroglycan and laminin 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 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>
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<p>Michele et al. (2002) showed that the posttranslational biochemical and functional disruption of alpha-dystroglycan in humans is recapitulated in the muscle and central nervous system of mutant myodystrophy (myd) mice, which have a mutation in the Large gene (603590). They demonstrated that myd mice have abnormal neuronal migration in the cerebral cortex, cerebellum, and hippocampus, and show disruption of the basal lamina. In addition, dystroglycan in myd mice targets proteins to functional sites in brain through its interactions with extracellular matrix proteins. Michele et al. (2002) suggested that at least 3 mammalian genes function within a convergent posttranslational processing pathway during the biosynthesis of dystroglycan and that abnormal dystroglycan-ligand interactions underlie the pathogenic mechanism of muscular dystrophy with brain abnormalities. </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 (see 156225)-binding levels to be 50% of normal. In contrast, intact alpha-dystroglycan was undetectable in the dystrophic Large(myd) mouse, 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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<strong>See Also:</strong>
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<span class="mim-text-font">
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Murakami et al. (1975)
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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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Am. J. Med. Genet. 138A: 344-348, 2005.
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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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Yoshioka, M., Kuroki, S.
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<strong>Clinical spectrum and genetic studies of Fukuyama congenital muscular dystrophy.</strong>
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Am. J. Med. Genet. 53: 245-250, 1994.
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[PubMed: 7856660]
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[Full Text: https://doi.org/10.1002/ajmg.1320530309]
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Ada Hamosh - updated : 1/10/2012<br>Cassandra L. Kniffin - updated : 2/10/2011<br>Cassandra L. Kniffin - updated : 11/17/2010<br>Cassandra L. Kniffin - updated : 12/4/2009<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 7/12/2006<br>Cassandra L. Kniffin - updated : 3/9/2006<br>Cassandra L. Kniffin - updated : 5/7/2003<br>Victor A. McKusick - updated : 12/23/2002<br>Ada Hamosh - updated : 9/11/2002<br>George E. Tiller - updated : 3/5/2001<br>Victor A. McKusick - updated : 12/18/2000<br>Victor A. McKusick - updated : 5/22/2000<br>Victor A. McKusick - updated : 11/19/1999<br>Victor A. McKusick - updated : 8/12/1998<br>Victor A. McKusick - updated : 5/16/1997<br>Victor A. McKusick - updated : 3/16/1997<br>Moyra Smith - updated : 1/31/1997<br>Orest Hurko - updated : 9/27/1995
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Victor A. McKusick : 6/4/1986
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