2651 lines
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Entry
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- #271150 - SPINAL MUSCULAR ATROPHY, TYPE IV; SMA4
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- OMIM
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<p>
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<span class="h4">#271150</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/271150"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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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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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=SPINAL MUSCULAR ATROPHY, TYPE IV" 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=633&Typ=Pat" title="Proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Proximal spinal muscular a… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11567&Typ=Pat" title="Proximal spinal muscular atrophy type 4" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Proximal spinal muscular a… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1352/" 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/6737" 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/spinal-muscular-atrophy" 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=271150[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=70" title="Proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Proximal spinal muscular a…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83420" title="Proximal spinal muscular atrophy type 4" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Proximal spinal muscular a…</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0050529" 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/271150" 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://omia.org/OMIA000939/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050529" 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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<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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<a id="title" class="mim-anchor"></a>
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<a id="number" 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>ICD10CM:</strong> G12.1<br />
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<strong>ORPHA:</strong> 70, 83420<br />
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<strong>DO:</strong> 0050529<br />
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">ICD+</a>
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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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271150
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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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SPINAL MUSCULAR ATROPHY, TYPE IV; SMA4
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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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<a id="alternativeTitles" class="mim-anchor"></a>
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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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<div>
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<h4>
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<span class="mim-font">
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SPINAL MUSCULAR ATROPHY, ADULT FORM<br />
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SPINAL MUSCULAR ATROPHY, PROXIMAL, ADULT, AUTOSOMAL RECESSIVE
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</span>
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</h4>
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<br />
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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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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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<a href="/geneMap/5/232?start=-3&limit=10&highlight=232">
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5q13.2
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<span class="mim-font">
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Spinal muscular atrophy-4
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<span class="mim-font">
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<a href="/entry/271150"> 271150 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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SMN1
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<span class="mim-font">
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<a href="/entry/600354"> 600354 </a>
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<a href="/clinicalSynopsis/271150" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<span class="sr-only">Toggle Dropdown</span>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/271150" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/271150" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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<div style="margin-left: 2em;">
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- 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 />
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<span class="h5 mim-font">
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<strong> MUSCLE, SOFT TISSUES </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Hypertrophy of calves (in 3 of 6 patients) <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><br />
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</span>
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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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<div style="margin-left: 2em;">
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Muscle weakness, proximal, symmetric (lower limbs more affected than upper limbs) due to motor neuronopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854665&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854665</a>]</span><br /> -
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Muscle atrophy, proximal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850794</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007126</a>]</span><br /> -
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Tongue fasciculations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249878001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239548&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239548</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001308" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001308</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001308" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001308</a>]</span><br /> -
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Hand tremor <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239842&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239842</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002378</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002378</a>]</span><br /> -
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EMG shows neurogenic abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846832&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846832</a>]</span><br /> -
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Degeneration of spinal cord anterior horn cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843505&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843505</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002398" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002398</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002398" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002398</a>]</span><br /> -
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Areflexia in lower limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856694&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856694</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002522" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002522</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002522" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002522</a>]</span><br />
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</span>
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</div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Mean age at onset 35 years (range 20-60)<br /> -
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Slow disease progression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854494</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span><br /> -
|
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Allelic disorder to spinal muscular atrophy type I (<a href="/entry/253300">253300</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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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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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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- Caused by mutations in the survival of motor neuron 1 gene (SMN1, <a href="/entry/600354#0011">600354.0011</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">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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<div>
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<br />
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<div>
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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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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because autosomal recessive adult-onset spinal muscular atrophy type IV (SMA4) is caused by mutation or deletion in the SMN1 gene (<a href="/entry/600354">600354</a>) on chromosome 5q13.</p><p>Allelic disorders with overlapping phenotypes of differing severity and age at onset include SMA type I (<a href="/entry/253300">253300</a>), SMA type II (<a href="/entry/253550">253550</a>), and SMA type III (<a href="/entry/253400">253400</a>).</p>
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<br />
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<div>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Clinical Features</strong>
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<p><a href="#9" class="mim-tip-reference" title="Pearn, J. H., Hudgson, P., Walton, J. N. <strong>A clinical and genetic study of spinal muscular atrophy of adult onset.</strong> Brain 101: 591-606, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/737522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">737522</a>] [<a href="https://doi.org/10.1093/brain/101.4.591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="737522">Pearn et al. (1978)</a> described 9 patients from 6 families with adult-onset spinal muscular atrophy. The median age at onset was 35 years, and the mean age at initial medical presentation was 37 years. The condition was relatively benign, with symmetrical proximal muscle involvement and preservation of the distal musculature. Family studies suggested autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=737522" 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="#1" class="mim-tip-reference" title="Brahe, C., Servidei, S., Zappata, S., Ricci, E., Tonali, P., Neri, G. <strong>Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy.</strong> Lancet 346: 741-742, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7658877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7658877</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)91507-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7658877">Brahe et al. (1995)</a> reported 6 patients from 4 families with autosomal recessive adult-onset SMA. Age at onset ranged from 20 to 32 years, and symptoms included tongue fasciculations, hand tremor, symmetrical weakness of the proximal muscles that was more severe in the lower limbs, and atrophy of the quadriceps muscle. Three patients had bilateral hypertrophy of the calves. One patient was very mildly affected; 3 patients had done military service, apparently without problems. In a letter, <a href="#13" class="mim-tip-reference" title="Zerres, K., Rudnik-Schoneborn, S., Forkert, R., Wirth, B. <strong>Genetic basis of adult-onset spinal muscular atrophy. (Letter)</strong> Lancet 346: 1162 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7475624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7475624</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)91835-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7475624">Zerres et al. (1995)</a> noted that they defined SMA type IV as onset after age 30; patients with onset before age 30 years who retained the ability to walk were defined as having SMA type III. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7658877+7475624" 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="Clermont, O., Burlet, P., Lefebvre, S., Burglen, L., Munnich, A., Melki, J. <strong>SMN gene deletions in adult-onset spinal muscular atrophy. (Letter)</strong> Lancet 346: 1712-1713, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8551862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8551862</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)92881-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8551862">Clermont et al. (1995)</a> reported a 73-year-old woman who developed type IV SMA at age 47, with proximal muscle weakness, muscular atrophy, and patellar areflexia. Three of her 5 children had SMA type II, and all died before age 15 years. Molecular analysis showed that the mother had deletion of SMN exons 7 and 8 on both chromosomes, but no DNA from the children was available. <a href="#3" class="mim-tip-reference" title="Clermont, O., Burlet, P., Lefebvre, S., Burglen, L., Munnich, A., Melki, J. <strong>SMN gene deletions in adult-onset spinal muscular atrophy. (Letter)</strong> Lancet 346: 1712-1713, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8551862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8551862</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)92881-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8551862">Clermont et al. (1995)</a> concluded that adult and childhood SMA are allelic disorders, emphasizing the continuum of clinical phenotypes caused by SMN gene mutations and deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8551862" 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="#5" class="mim-tip-reference" title="Habets, L. E., Bartels, B., Asselman, F.-L., Hooijmans, M. T., van den Berg, S., Nederveen, A. J., van der Pol, W. L., Jeneson, J. A. L. <strong>Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.</strong> Brain 145: 1422-1435, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34788410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34788410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34788410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awab411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34788410">Habets et al. (2022)</a> evaluated the bioenergetic and structural characteristics of the biceps and triceps muscles in 14 patients with SMA type III and 1 patient with SMA type IV. MRIs demonstrated fatty infiltration in both triceps and biceps, which was greater in the triceps, and atrophy of the triceps muscles. Maximal voluntary contraction of force was reduced in both triceps and biceps muscles, and blood lactate increases after exercise were lower in patients compared to controls. 31P magnetic resonance spectroscopy studies identified white-to-red shift of muscle fiber types and slow metabolic recovery after exercise in white myofibers due to ATP synthetic dysfunction. <a href="#5" class="mim-tip-reference" title="Habets, L. E., Bartels, B., Asselman, F.-L., Hooijmans, M. T., van den Berg, S., Nederveen, A. J., van der Pol, W. L., Jeneson, J. A. L. <strong>Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.</strong> Brain 145: 1422-1435, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34788410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34788410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34788410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awab411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34788410">Habets et al. (2022)</a> concluded that these findings demonstrated the disproportionate vulnerability of white myofibers to SMN protein depletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34788410" 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="Weihl, C. C., Connolly, A. M., Pestronk, A. <strong>Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy.</strong> Neurology 67: 500-501, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16775228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16775228</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231139.26253.d0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16775228">Weihl et al. (2006)</a> reported increased quantitative muscle strength and subjective function in 7 adult patients with SMA3/SMA4 who were treated with oral valproate for a mean duration of 8 months. Most patients reported improvement within a few months of beginning treatment. The authors noted that previous studies (see <a href="#2" class="mim-tip-reference" title="Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B. <strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong> Hum. Molec. Genet. 12: 2481-2489, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915451</a>] [<a href="https://doi.org/10.1093/hmg/ddg256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12915451">Brichta et al., 2003</a>) had suggested that inhibitors of histone deacetylase, such as valproate, may increase SMN2 (<a href="/entry/601627">601627</a>) gene transcription and result in increased production of full-length SMN protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12915451+16775228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 6 patients with SMA4, <a href="#1" class="mim-tip-reference" title="Brahe, C., Servidei, S., Zappata, S., Ricci, E., Tonali, P., Neri, G. <strong>Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy.</strong> Lancet 346: 741-742, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7658877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7658877</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)91507-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7658877">Brahe et al. (1995)</a> identified deletion of exons 7 and 8 of the SMN1 gene, indicating that autosomal recessive adult SMA is allelic to the childhood forms of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7658877" 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="Mazzei, R., Gambardella, A., Conforti, F. L., Magariello, A., Patitucci, A., Gabriele, A. L., Sprovieri, T., Labate, A., Valentino, P., Bono, F., Bonavita, S., Zappia, M., Muglia, M., Quattrone, A. <strong>Gene conversion events in adult-onset spinal muscular atrophy.</strong> Acta Neurol. Scand. 109: 151-154, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14705979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14705979</a>] [<a href="https://doi.org/10.1034/j.1600-0404.2003.00181.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14705979">Mazzei et al. (2004)</a> found evidence for a gene conversion event in SMN1 in 3 patients with SMA4, supporting the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later age at disease onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14705979" 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>Modifying Factors</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Wirth, B., Brichta, L., Schrank, B., Lochmuller, H., Blick, S., Baasner, A., Heller, R. <strong>Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number.</strong> Hum. Genet. 119: 422-428, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16508748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16508748</a>] [<a href="https://doi.org/10.1007/s00439-006-0156-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16508748">Wirth et al. (2006)</a> analyzed SMN2 copy number in 115 patients with SMA3 or SMA4 who had confirmed homozygous absence of SMN1 and found that 62% of SMA3 patients with age of onset less than 3 years had 2 or 3 SMN2 copies, whereas 65% of SMA3 patients with age of onset greater than 3 years had 4 to 5 SMN2 copies. Of the 4 adult-onset (SMA4) patients, 3 had 4 SMN2 copies and 1 had 6 copies. <a href="#12" class="mim-tip-reference" title="Wirth, B., Brichta, L., Schrank, B., Lochmuller, H., Blick, S., Baasner, A., Heller, R. <strong>Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number.</strong> Hum. Genet. 119: 422-428, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16508748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16508748</a>] [<a href="https://doi.org/10.1007/s00439-006-0156-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16508748">Wirth et al. (2006)</a> concluded that SMN2 may have a disease-modifying role in SMA, with a greater SMN2 copy number associated with later onset and better prognosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16508748" 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>Heterogeneity</em></strong></p><p>
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<a href="#6" class="mim-tip-reference" title="Hahnen, E., Forkert, R., Marke, C., Rudnik-Schoneborn, S., Schonling, J., Zerres, K., Wirth, B. <strong>Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals.</strong> Hum. Molec. Genet. 4: 1927-1933, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595417</a>] [<a href="https://doi.org/10.1093/hmg/4.10.1927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8595417">Hahnen et al. (1995)</a> reported 4 patients with onset of SMA after age 30 who showed no homozygous deletion of exons 7 and 8 of the SMN1 gene, suggesting genetic heterogeneity. However, the 4 patients with presumed SMA IV had no family history, and spontaneous autosomal dominant mutation at a different locus could not be excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8595417" 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>Although human SMN1 and SMN2 both encode the SMN protein, the SMN2 gene is unable to compensate for the loss of SMN1 protein in SMA patients. A translationally silent T at nucleotide +6 of SMN2 exon 7 instead of SMN1's C causes the final RNA product to be improperly regulated, with the majority of SMN2 pre-mRNA transcripts lacking exon 7. While humans have both SMN1 and SMN2 genes, mice and other mammals have only a single Smn gene. Using mouse and human SMN minigenes and homologous recombination, <a href="#4" class="mim-tip-reference" title="Gladman, J. T., Bebee, T. W., Edwards, C., Wang, X., Sahenk, Z., Rich, M. M., Chandler, D. S. <strong>A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype.</strong> Hum. Molec. Genet. 19: 4239-4252, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705738[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/ddq343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20705738">Gladman et al. (2010)</a> created a mouse model of SMA by inserting the SMN2 C-to-T nucleotide alteration into the endogenous mouse Smn gene. The C-to-T mutation was sufficient to induce exon 7 skipping in the mouse minigene as in the human SMN2. When the mouse Smn gene was humanized to carry the C-to-T mutation, keeping it under the control of the endogenous promoter, and in the natural genomic context, the resulting mice exhibited exon 7 skipping and mild adult-onset SMA characterized by muscle weakness, decreased activity, and an alteration of muscle fiber size. <a href="#4" class="mim-tip-reference" title="Gladman, J. T., Bebee, T. W., Edwards, C., Wang, X., Sahenk, Z., Rich, M. M., Chandler, D. S. <strong>A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype.</strong> Hum. Molec. Genet. 19: 4239-4252, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705738[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/ddq343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20705738">Gladman et al. (2010)</a> proposed that the Smn C-to-T mouse is a model for the adult-onset form of SMA (type III/IV) known as Kugelberg-Welander disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20705738" 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="#Mapelli1970" class="mim-tip-reference" title="Mapelli, G., Ramelli, E. <strong>Familial progressive spinal amyotrophy with limb root distribution and onset in adult life (neurogenic pseudomyopathy of Wohlfart-Kugelberg-Welander). In: Waston, J. N.; Canal, N.; Scorlato, G. (eds.): Muscle Diseases.</strong> Amsterdam: Excerpta Medica (pub.) 1970.">Mapelli and Ramelli (1970)</a>; <a href="#Tsukagoshi1965" class="mim-tip-reference" title="Tsukagoshi, H., Nakanishi, T., Kondo, K., Tsubaki, T. <strong>Hereditary proximal neurogenic muscular atrophy in adults.</strong> Arch. Neurol. 12: 597-603, 1965.">Tsukagoshi et al. (1965)</a>
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[<a href="https://doi.org/10.1016/s0140-6736(95)91507-9" target="_blank">Full Text</a>]
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<a id="Brichta2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B.
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<strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong>
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Hum. Molec. Genet. 12: 2481-2489, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915451" 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/ddg256" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Clermont1995" class="mim-anchor"></a>
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<p class="mim-text-font">
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Clermont, O., Burlet, P., Lefebvre, S., Burglen, L., Munnich, A., Melki, J.
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<strong>SMN gene deletions in adult-onset spinal muscular atrophy. (Letter)</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8551862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8551862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8551862" 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/s0140-6736(95)92881-2" target="_blank">Full Text</a>]
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<a id="Gladman2010" class="mim-anchor"></a>
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<div class="">
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Gladman, J. T., Bebee, T. W., Edwards, C., Wang, X., Sahenk, Z., Rich, M. M., Chandler, D. S.
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<strong>A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype.</strong>
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Hum. Molec. Genet. 19: 4239-4252, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705738[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=20705738" 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/ddq343" target="_blank">Full Text</a>]
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<a id="Habets2022" class="mim-anchor"></a>
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Habets, L. E., Bartels, B., Asselman, F.-L., Hooijmans, M. T., van den Berg, S., Nederveen, A. J., van der Pol, W. L., Jeneson, J. A. L.
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<strong>Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.</strong>
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Brain 145: 1422-1435, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34788410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34788410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34788410[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=34788410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awab411" target="_blank">Full Text</a>]
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<a id="Hahnen1995" class="mim-anchor"></a>
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Hahnen, E., Forkert, R., Marke, C., Rudnik-Schoneborn, S., Schonling, J., Zerres, K., Wirth, B.
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<strong>Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals.</strong>
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Hum. Molec. Genet. 4: 1927-1933, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595417</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8595417" 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/4.10.1927" target="_blank">Full Text</a>]
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Mapelli, G., Ramelli, E.
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<strong>Familial progressive spinal amyotrophy with limb root distribution and onset in adult life (neurogenic pseudomyopathy of Wohlfart-Kugelberg-Welander). In: Waston, J. N.; Canal, N.; Scorlato, G. (eds.): Muscle Diseases.</strong>
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Amsterdam: Excerpta Medica (pub.) 1970.
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Mazzei, R., Gambardella, A., Conforti, F. L., Magariello, A., Patitucci, A., Gabriele, A. L., Sprovieri, T., Labate, A., Valentino, P., Bono, F., Bonavita, S., Zappia, M., Muglia, M., Quattrone, A.
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<strong>Gene conversion events in adult-onset spinal muscular atrophy.</strong>
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Acta Neurol. Scand. 109: 151-154, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14705979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14705979</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14705979" 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/10.1034/j.1600-0404.2003.00181.x" target="_blank">Full Text</a>]
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<a id="Pearn1978" class="mim-anchor"></a>
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Pearn, J. H., Hudgson, P., Walton, J. N.
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<strong>A clinical and genetic study of spinal muscular atrophy of adult onset.</strong>
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Brain 101: 591-606, 1978.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/737522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">737522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=737522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/101.4.591" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Tsukagoshi1965" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tsukagoshi, H., Nakanishi, T., Kondo, K., Tsubaki, T.
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<strong>Hereditary proximal neurogenic muscular atrophy in adults.</strong>
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Arch. Neurol. 12: 597-603, 1965.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14295959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14295959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14295959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.1965.00460300045005" target="_blank">Full Text</a>]
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<a id="Weihl2006" class="mim-anchor"></a>
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Weihl, C. C., Connolly, A. M., Pestronk, A.
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<strong>Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy.</strong>
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Neurology 67: 500-501, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16775228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16775228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16775228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000231139.26253.d0" target="_blank">Full Text</a>]
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<a id="Wirth2006" class="mim-anchor"></a>
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Wirth, B., Brichta, L., Schrank, B., Lochmuller, H., Blick, S., Baasner, A., Heller, R.
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<strong>Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number.</strong>
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Hum. Genet. 119: 422-428, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16508748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16508748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16508748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-006-0156-7" target="_blank">Full Text</a>]
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<a id="Zerres1995" class="mim-anchor"></a>
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Zerres, K., Rudnik-Schoneborn, S., Forkert, R., Wirth, B.
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<strong>Genetic basis of adult-onset spinal muscular atrophy. (Letter)</strong>
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Lancet 346: 1162 only, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7475624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7475624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7475624" 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/s0140-6736(95)91835-3" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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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Hilary J. Vernon - updated : 08/25/2022
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 06/26/2017<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Cassandra L. Kniffin - reorganized : 3/31/2004
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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alopez : 06/26/2017<br>carol : 03/25/2017<br>wwang : 08/21/2007<br>ckniffin : 8/3/2007<br>wwang : 8/15/2006<br>terry : 8/11/2006<br>carol : 3/31/2004<br>ckniffin : 3/29/2004<br>warfield : 4/20/1994<br>mimadm : 3/12/1994<br>carol : 1/15/1993<br>supermim : 3/17/1992<br>carol : 7/24/1991<br>supermim : 3/20/1990
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<strong>#</strong> 271150
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SPINAL MUSCULAR ATROPHY, TYPE IV; SMA4
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SPINAL MUSCULAR ATROPHY, ADULT FORM<br />
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SPINAL MUSCULAR ATROPHY, PROXIMAL, ADULT, AUTOSOMAL RECESSIVE
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<strong>ICD10CM:</strong> G12.1;
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<strong>ORPHA:</strong> 70, 83420;
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<strong>DO:</strong> 0050529;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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 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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5q13.2
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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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Spinal muscular atrophy-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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271150
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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SMN1
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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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600354
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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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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because autosomal recessive adult-onset spinal muscular atrophy type IV (SMA4) is caused by mutation or deletion in the SMN1 gene (600354) on chromosome 5q13.</p><p>Allelic disorders with overlapping phenotypes of differing severity and age at onset include SMA type I (253300), SMA type II (253550), and SMA type III (253400).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Pearn et al. (1978) described 9 patients from 6 families with adult-onset spinal muscular atrophy. The median age at onset was 35 years, and the mean age at initial medical presentation was 37 years. The condition was relatively benign, with symmetrical proximal muscle involvement and preservation of the distal musculature. Family studies suggested autosomal recessive inheritance. </p><p>Brahe et al. (1995) reported 6 patients from 4 families with autosomal recessive adult-onset SMA. Age at onset ranged from 20 to 32 years, and symptoms included tongue fasciculations, hand tremor, symmetrical weakness of the proximal muscles that was more severe in the lower limbs, and atrophy of the quadriceps muscle. Three patients had bilateral hypertrophy of the calves. One patient was very mildly affected; 3 patients had done military service, apparently without problems. In a letter, Zerres et al. (1995) noted that they defined SMA type IV as onset after age 30; patients with onset before age 30 years who retained the ability to walk were defined as having SMA type III. </p><p>Clermont et al. (1995) reported a 73-year-old woman who developed type IV SMA at age 47, with proximal muscle weakness, muscular atrophy, and patellar areflexia. Three of her 5 children had SMA type II, and all died before age 15 years. Molecular analysis showed that the mother had deletion of SMN exons 7 and 8 on both chromosomes, but no DNA from the children was available. Clermont et al. (1995) concluded that adult and childhood SMA are allelic disorders, emphasizing the continuum of clinical phenotypes caused by SMN gene mutations and deletions. </p><p>Habets et al. (2022) evaluated the bioenergetic and structural characteristics of the biceps and triceps muscles in 14 patients with SMA type III and 1 patient with SMA type IV. MRIs demonstrated fatty infiltration in both triceps and biceps, which was greater in the triceps, and atrophy of the triceps muscles. Maximal voluntary contraction of force was reduced in both triceps and biceps muscles, and blood lactate increases after exercise were lower in patients compared to controls. 31P magnetic resonance spectroscopy studies identified white-to-red shift of muscle fiber types and slow metabolic recovery after exercise in white myofibers due to ATP synthetic dysfunction. Habets et al. (2022) concluded that these findings demonstrated the disproportionate vulnerability of white myofibers to SMN protein depletion. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Weihl et al. (2006) reported increased quantitative muscle strength and subjective function in 7 adult patients with SMA3/SMA4 who were treated with oral valproate for a mean duration of 8 months. Most patients reported improvement within a few months of beginning treatment. The authors noted that previous studies (see Brichta et al., 2003) had suggested that inhibitors of histone deacetylase, such as valproate, may increase SMN2 (601627) gene transcription and result in increased production of full-length SMN protein. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 6 patients with SMA4, Brahe et al. (1995) identified deletion of exons 7 and 8 of the SMN1 gene, indicating that autosomal recessive adult SMA is allelic to the childhood forms of SMA. </p><p>Mazzei et al. (2004) found evidence for a gene conversion event in SMN1 in 3 patients with SMA4, supporting the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later age at disease onset. </p><p><strong><em>Modifying Factors</em></strong></p><p>
|
|
Wirth et al. (2006) analyzed SMN2 copy number in 115 patients with SMA3 or SMA4 who had confirmed homozygous absence of SMN1 and found that 62% of SMA3 patients with age of onset less than 3 years had 2 or 3 SMN2 copies, whereas 65% of SMA3 patients with age of onset greater than 3 years had 4 to 5 SMN2 copies. Of the 4 adult-onset (SMA4) patients, 3 had 4 SMN2 copies and 1 had 6 copies. Wirth et al. (2006) concluded that SMN2 may have a disease-modifying role in SMA, with a greater SMN2 copy number associated with later onset and better prognosis. </p><p><strong><em>Heterogeneity</em></strong></p><p>
|
|
Hahnen et al. (1995) reported 4 patients with onset of SMA after age 30 who showed no homozygous deletion of exons 7 and 8 of the SMN1 gene, suggesting genetic heterogeneity. However, the 4 patients with presumed SMA IV had no family history, and spontaneous autosomal dominant mutation at a different locus could not be excluded. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Although human SMN1 and SMN2 both encode the SMN protein, the SMN2 gene is unable to compensate for the loss of SMN1 protein in SMA patients. A translationally silent T at nucleotide +6 of SMN2 exon 7 instead of SMN1's C causes the final RNA product to be improperly regulated, with the majority of SMN2 pre-mRNA transcripts lacking exon 7. While humans have both SMN1 and SMN2 genes, mice and other mammals have only a single Smn gene. Using mouse and human SMN minigenes and homologous recombination, Gladman et al. (2010) created a mouse model of SMA by inserting the SMN2 C-to-T nucleotide alteration into the endogenous mouse Smn gene. The C-to-T mutation was sufficient to induce exon 7 skipping in the mouse minigene as in the human SMN2. When the mouse Smn gene was humanized to carry the C-to-T mutation, keeping it under the control of the endogenous promoter, and in the natural genomic context, the resulting mice exhibited exon 7 skipping and mild adult-onset SMA characterized by muscle weakness, decreased activity, and an alteration of muscle fiber size. Gladman et al. (2010) proposed that the Smn C-to-T mouse is a model for the adult-onset form of SMA (type III/IV) known as Kugelberg-Welander disease. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Mapelli and Ramelli (1970); Tsukagoshi et al. (1965)
|
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</span>
|
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<div>
|
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<br />
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|
</div>
|
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
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<div>
|
|
<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Brahe, C., Servidei, S., Zappata, S., Ricci, E., Tonali, P., Neri, G.
|
|
<strong>Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy.</strong>
|
|
Lancet 346: 741-742, 1995.
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|
[PubMed: 7658877]
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[Full Text: https://doi.org/10.1016/s0140-6736(95)91507-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B.
|
|
<strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 12: 2481-2489, 2003.
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[PubMed: 12915451]
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[Full Text: https://doi.org/10.1093/hmg/ddg256]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Clermont, O., Burlet, P., Lefebvre, S., Burglen, L., Munnich, A., Melki, J.
|
|
<strong>SMN gene deletions in adult-onset spinal muscular atrophy. (Letter)</strong>
|
|
Lancet 346: 1712-1713, 1995.
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[PubMed: 8551862]
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[Full Text: https://doi.org/10.1016/s0140-6736(95)92881-2]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gladman, J. T., Bebee, T. W., Edwards, C., Wang, X., Sahenk, Z., Rich, M. M., Chandler, D. S.
|
|
<strong>A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype.</strong>
|
|
Hum. Molec. Genet. 19: 4239-4252, 2010.
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[PubMed: 20705738]
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[Full Text: https://doi.org/10.1093/hmg/ddq343]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Habets, L. E., Bartels, B., Asselman, F.-L., Hooijmans, M. T., van den Berg, S., Nederveen, A. J., van der Pol, W. L., Jeneson, J. A. L.
|
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<strong>Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.</strong>
|
|
Brain 145: 1422-1435, 2022.
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[PubMed: 34788410]
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[Full Text: https://doi.org/10.1093/brain/awab411]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Hahnen, E., Forkert, R., Marke, C., Rudnik-Schoneborn, S., Schonling, J., Zerres, K., Wirth, B.
|
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<strong>Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals.</strong>
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Hum. Molec. Genet. 4: 1927-1933, 1995.
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[PubMed: 8595417]
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[Full Text: https://doi.org/10.1093/hmg/4.10.1927]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Mapelli, G., Ramelli, E.
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<strong>Familial progressive spinal amyotrophy with limb root distribution and onset in adult life (neurogenic pseudomyopathy of Wohlfart-Kugelberg-Welander). In: Waston, J. N.; Canal, N.; Scorlato, G. (eds.): Muscle Diseases.</strong>
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Amsterdam: Excerpta Medica (pub.) 1970.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mazzei, R., Gambardella, A., Conforti, F. L., Magariello, A., Patitucci, A., Gabriele, A. L., Sprovieri, T., Labate, A., Valentino, P., Bono, F., Bonavita, S., Zappia, M., Muglia, M., Quattrone, A.
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<strong>Gene conversion events in adult-onset spinal muscular atrophy.</strong>
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Acta Neurol. Scand. 109: 151-154, 2004.
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[PubMed: 14705979]
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[Full Text: https://doi.org/10.1034/j.1600-0404.2003.00181.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Pearn, J. H., Hudgson, P., Walton, J. N.
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<strong>A clinical and genetic study of spinal muscular atrophy of adult onset.</strong>
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Brain 101: 591-606, 1978.
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[PubMed: 737522]
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[Full Text: https://doi.org/10.1093/brain/101.4.591]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Tsukagoshi, H., Nakanishi, T., Kondo, K., Tsubaki, T.
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<strong>Hereditary proximal neurogenic muscular atrophy in adults.</strong>
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Arch. Neurol. 12: 597-603, 1965.
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[PubMed: 14295959]
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[Full Text: https://doi.org/10.1001/archneur.1965.00460300045005]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Weihl, C. C., Connolly, A. M., Pestronk, A.
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<strong>Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy.</strong>
|
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Neurology 67: 500-501, 2006.
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[PubMed: 16775228]
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[Full Text: https://doi.org/10.1212/01.wnl.0000231139.26253.d0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Wirth, B., Brichta, L., Schrank, B., Lochmuller, H., Blick, S., Baasner, A., Heller, R.
|
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<strong>Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number.</strong>
|
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Hum. Genet. 119: 422-428, 2006.
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[PubMed: 16508748]
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[Full Text: https://doi.org/10.1007/s00439-006-0156-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Zerres, K., Rudnik-Schoneborn, S., Forkert, R., Wirth, B.
|
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<strong>Genetic basis of adult-onset spinal muscular atrophy. (Letter)</strong>
|
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Lancet 346: 1162 only, 1995.
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[PubMed: 7475624]
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[Full Text: https://doi.org/10.1016/s0140-6736(95)91835-3]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Hilary J. Vernon - updated : 08/25/2022<br>George E. Tiller - updated : 06/26/2017<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Cassandra L. Kniffin - reorganized : 3/31/2004
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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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<br />
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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</div>
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<div>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Edit History:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/25/2022<br>alopez : 06/26/2017<br>carol : 03/25/2017<br>wwang : 08/21/2007<br>ckniffin : 8/3/2007<br>wwang : 8/15/2006<br>terry : 8/11/2006<br>carol : 3/31/2004<br>ckniffin : 3/29/2004<br>warfield : 4/20/1994<br>mimadm : 3/12/1994<br>carol : 1/15/1993<br>supermim : 3/17/1992<br>carol : 7/24/1991<br>supermim : 3/20/1990
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