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<title>
Entry
- #256030 - NEMALINE MYOPATHY 2; NEM2
- OMIM
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<span class="h4">#256030</span>
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<strong>Table of Contents</strong>
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<li role="presentation">
<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
<a href="/clinicalSynopsis/256030"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
<a href="/phenotypicSeries/PS161800"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#history">History</a>
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<a href="#animalModel">Animal Model</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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<div><a href="https://clinicaltrials.gov/search?cond=(NEMALINE MYOPATHY) OR (NEB)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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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=17906&Typ=Pat" title="Severe congenital nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Severe congenital nemaline…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17907&Typ=Pat" title="Intermediate nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Intermediate nemaline myop…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17908&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Typical nemaline myopathy&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17909&Typ=Pat" title="Childhood-onset nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Childhood-onset nemaline m…&nbsp;</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5124" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=256030[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 style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171430" title="Severe congenital nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Severe congenital nemaline…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171433" title="Intermediate nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Intermediate nemaline myop…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Typical nemaline myopathy</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171439" title="Childhood-onset nemaline myopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Childhood-onset nemaline m…</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/91a06564-e392-41f6-b53e-5016c4c1b6b4/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:256030" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ORPHA:</strong> 171430, 171433, 171436, 171439<br />
<strong>DO:</strong> 0110928<br />
">ICD+</a>
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<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
256030
</span>
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<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
NEMALINE MYOPATHY 2; NEM2
</span>
</h3>
</div>
<div>
<br />
</div>
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<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/688?start=-3&limit=10&highlight=688">
2q23.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Nemaline myopathy 2, autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/256030"> 256030 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
NEB
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161650"> 161650 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="/clinicalSynopsis/256030" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/256030" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </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>
<div>
<p />
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Myopathic facies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26432009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26432009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0332615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332615</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span><br /> -
Facial muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95666008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95666008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R29.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R29.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.83</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/781.94" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.94</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007209</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- High-arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Neck flexor muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843637&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843637</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003722" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003722</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003722" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003722</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Respiratory insufficiency due to muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806467</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002747</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002747</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Chest deformities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238983&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238983</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor feeding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</a>, <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br /> -
Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Joint contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7890003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7890003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/718.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.4</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/718.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034392" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034392</a>]</span><br /> -
Joint deformities (may develop over time) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850588</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hyperlordosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61960001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61960001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249710008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249710008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187290008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187290008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024003&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024003</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003307</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003307</a>]</span><br /> -
Scoliosis (onset around puberty) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850590&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850590</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br /> -
Rigid spine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858025&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858025</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia, neonatal <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205294008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2267233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2267233</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span><br /> -
Muscle weakness, generalized <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/728.87" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">728.87</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0746674&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0746674</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003324</a>]</span><br /> -
Bulbar muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398432008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398432008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1301959&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1301959</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001283" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001283</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001283" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001283</a>]</span><br /> -
Facial muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95666008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95666008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R29.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R29.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.83</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/781.94" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.94</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007209</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span><br /> -
Neck muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</a>]</span><br /> -
Proximal limb muscle weakness (initially) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850580&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850580</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249939004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span><br /> -
Distal limb muscle weakness (occurs later) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864972</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249942005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span><br /> -
Distal limb muscle weakness (initially, in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249942005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427065&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427065</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span><br /> -
'Waddling' gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271706000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271706000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231712&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231712</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002515</a>]</span><br /> -
Inability to run <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854490</a>]</span><br /> -
Inability to walk on heels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866141&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866141</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009027</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009027</a>]</span><br /> -
Frequent falls <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0850703&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0850703</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002359" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002359</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002359" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002359</a>]</span><br /> -
Myopathic changes early in disease seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278556&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278556</a>]</span><br /> -
Neurogenic changes later in disease seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278557&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278557</a>]</span><br /> -
Nemaline bodies (rods) seen on Gomori trichrome staining <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5677934&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5677934</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003798" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003798</a>]</span><br /> -
Nemaline bodies are usually subsarcolemmal or sarcoplasmic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850583</a>]</span><br /> -
Nemaline bodies are rarely intranuclear <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850584</a>]</span><br /> -
Nonspecific myopathic changes without dystrophic or inflammatory changes seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805774&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805774</a>]</span><br /> -
Cores with lack of oxidative activity and mitochondrial depletion may also be found and extend along length of fiber <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278559&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278559</a>]</span><br /> -
Type 1 muscle fiber predominance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854387&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854387</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003803" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003803</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003803" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003803</a>]</span><br /> -
Decreased muscle density on imaging <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850585&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850585</a>]</span><br /> -
Increased fatty infiltration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850586&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850586</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed motor development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br /> -
Absent gag reflex <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5258001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5258001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234784</a>]</span><br /> -
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
Slow gross motor activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850571&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850571</a>]</span><br /> -
Normal fine motor activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850572</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Normal or mildly increased serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864981</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Extraocular muscles are not involved<br /> -
Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
Highly variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866862</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
Slowly progressive or nonprogressive course<br /> -
Many adults with typical form remain ambulatory<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the nebulin gene (NEB, <a href="/entry/161650#0001">161650.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Nemaline myopathy
- <a href="/phenotypicSeries/PS161800">PS161800</a>
- 13 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1184?start=-3&limit=10&highlight=1184"> 1q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609284"> Congenital myopathy 4B, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609284"> 609284 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> TPM3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> 191030 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1785?start=-3&limit=10&highlight=1785"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161800"> Congenital myopathy 2A, typical, autosomal dominant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161800"> 161800 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> ACTA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> 102610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/688?start=-3&limit=10&highlight=688"> 2q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/256030"> Nemaline myopathy 2, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/256030"> 256030 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161650"> NEB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161650"> 161650 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/758?start=-3&limit=10&highlight=758"> 2q31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615731"> Nemaline myopathy 9 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615731"> 615731 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607701"> KLHL41 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607701"> 607701 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/208?start=-3&limit=10&highlight=208"> 3p22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615348"> Nemaline myopathy 8, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615348"> 615348 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615340"> KLHL40 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615340"> 615340 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/452?start=-3&limit=10&highlight=452"> 3p14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616165"> Nemaline myopathy 10 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616165"> 616165 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616112"> LMOD3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616112"> 616112 </a>
</span>
</td>
</tr>
<tr>
<td>
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<a href="/entry/609285"> Congenital myopathy 23 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<a href="/entry/190990"> TPM2 </a>
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<a href="/entry/617336"> Congenital myopathy 24 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<a href="/entry/610687"> Nemaline myopathy 7, autosomal recessive </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<a href="/entry/609273"> Nemaline myopathy 6, autosomal dominant </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<a href="/entry/613727"> 613727 </a>
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<a href="/entry/605355"> Nemaline myopathy 5A, autosomal recessive, severe infantile </a>
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<span class="mim-font">
<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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<a href="/entry/191041"> 191041 </a>
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<a href="/entry/620389"> Nemaline myopathy 5C, autosomal dominant </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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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<a href="/entry/620389"> 620389 </a>
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<a href="/entry/191041"> TNNT1 </a>
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<a href="/entry/191041"> 191041 </a>
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<a href="/geneMap/19/1155?start=-3&limit=10&highlight=1155"> 19q13.42 </a>
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<a href="/entry/620386"> Nemaline myopathy 5B, autosomal recessive, childhood-onset </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
<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">
<a href="/entry/620386"> 620386 </a>
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<span class="mim-font">
<a href="/entry/191041"> TNNT1 </a>
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<span class="mim-font">
<a href="/entry/191041"> 191041 </a>
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<p>A number sign (#) is used with this entry because of evidence that nemaline myopathy-2 (NEM2) is caused by homozygous or compound heterozygous mutation in the nebulin gene (NEB; <a href="/entry/161650">161650</a>) on chromosome 2q23.</p><p>Biallelic mutation in the NEB gene can also cause arthrogryposis multiplex congenita-6 (AMC6; <a href="/entry/619334">619334</a>), which is much more severe and usually results in early death.</p>
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<p>Nemaline myopathy-2 (NEM2) is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by <a href="#15" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. &lt;strong&gt;Mutation update: the spectra of nebulin variants and associated myopathies.&lt;/strong&gt; Hum. Mutat. 35: 1418-1426, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25205138/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25205138&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25205138[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25205138">Lehtokari et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" 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>Genetic Heterogeneity of Nemaline Myopathy</em></strong>
</p>
<div class="mim-changed mim-change"><p>See also NEM1 (<a href="/entry/255310">255310</a>), caused by mutation in the tropomyosin-3 gene (TPM3; <a href="/entry/191030">191030</a>) on chromosome 1q21; NEM3 (<a href="/entry/161800">161800</a>), caused by mutation in the alpha-actin-1 gene (ACTA1; <a href="/entry/102610">102610</a>) on chromosome 1q42; NEM4 (<a href="/entry/609285">609285</a>), caused by mutation in the beta-tropomyosin gene (TPM2; <a href="/entry/190990">190990</a>) on chromosome 9p13; NEM5A (<a href="/entry/605355">605355</a>), also known as Amish nemaline myopathy, NEM5B (<a href="/entry/620386">620386</a>), and NEM5C (<a href="/entry/620389">620389</a>), all caused by mutation in the troponin T1 gene (TNNT1; <a href="/entry/191041">191041</a>) on chromosome 19q13; NEM6 (<a href="/entry/609273">609273</a>), caused by mutation in the KBTBD13 gene (<a href="/entry/613727">613727</a>) on chromosome 15q22; NEM7 (<a href="/entry/610687">610687</a>), caused by mutation in the cofilin-2 gene (CFL2; <a href="/entry/601443">601443</a>) on chromosome 14q13; NEM8 (<a href="/entry/615348">615348</a>), caused by mutation in the KLHL40 gene (<a href="/entry/615340">615340</a>), on chromosome 3p22; NEM9 (<a href="/entry/615731">615731</a>), caused by mutation in the KLHL41 gene (<a href="/entry/607701">607701</a>) on chromosome 2q31; NEM10 (<a href="/entry/616165">616165</a>), caused by mutation in the LMOD3 gene (<a href="/entry/616112">616112</a>) on chromosome 3p14; and NEM11 (<a href="/entry/617336">617336</a>), caused by mutation in the MYPN gene (<a href="/entry/608517">608517</a>) on chromosome 10q21. Several of the genes encode components of skeletal muscle sarcomeric thin filaments (<a href="#28" class="mim-tip-reference" title="Sanoudou, D., Beggs, A. H. &lt;strong&gt;Clinical and genetic heterogeneity in nemaline myopathy--a disease of skeletal muscle thin filaments.&lt;/strong&gt; Trends Molec. Med. 7: 362-368, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11516997/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11516997&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s1471-4914(01)02089-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11516997">Sanoudou and Beggs, 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11516997" 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></div>
<p>Mutations in the NEB gene are the most common cause of nemaline myopathy (<a href="#16" class="mim-tip-reference" title="Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C. &lt;strong&gt;Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.&lt;/strong&gt; Hum. Mutat. 27: 946-956, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16917880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16917880&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20370&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16917880">Lehtokari et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917880" 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="#36" class="mim-tip-reference" title="Wallgren-Pettersson, C., Pelin, K., Hilpela, P., Donner, K., Porfirio, B., Graziano, C., Swoboda, K. J., Fardeau, M., Urtizberea, J. A., Muntoni, F., Sewry, C., Dubowitz, V., and 10 others. &lt;strong&gt;Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy.&lt;/strong&gt; Neuromusc. Disord. 9: 564-572, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10619714/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10619714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(99)00061-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10619714">Wallgren-Pettersson et al. (1999)</a> reported 41 unrelated families with NEM2 suggested by linkage analysis. All were consistent with autosomal recessive inheritance. <a href="#36" class="mim-tip-reference" title="Wallgren-Pettersson, C., Pelin, K., Hilpela, P., Donner, K., Porfirio, B., Graziano, C., Swoboda, K. J., Fardeau, M., Urtizberea, J. A., Muntoni, F., Sewry, C., Dubowitz, V., and 10 others. &lt;strong&gt;Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy.&lt;/strong&gt; Neuromusc. Disord. 9: 564-572, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10619714/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10619714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(99)00061-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10619714">Wallgren-Pettersson et al. (1999)</a> noted that phenotypic classification of nemaline myopathy is difficult because the disease spectrum forms a continuum; however, the authors described 2 main forms associated with NEB mutations: 'typical,' consistent with NEM2, and 'severe,' consistent with AMC6. Typical patients had generalized hypotonia at birth, with particular involvement of the bulbar, neck flexor, and respiratory muscles. Proximal limb muscles were weaker initially, but distal limb muscle weakness eventually occurred. The extraocular muscles were spared. The facies was myopathic with a high-arched palate. The spine was hyperlordotic, sometimes rigid, and scoliosis sometimes developed at puberty. Deep tendon reflexes were decreased or absent, and the gag reflex was often absent. Chest deformities were common, but there was no cardiac involvement. Imaging showed decreased muscle density with increased fatty infiltration. Serum creatine kinase was normal or mildly elevated. Muscle biopsies characteristically showed nemaline bodies and type 1 fiber predominance. Although myopathic changes were observed, there were no dystrophic or inflammatory changes. Despite delayed motor development and waddling gait, many patients with typical disease remained ambulatory as adults. Intelligence was normal. A subset of patients had severe disease characterized by absence of spontaneous movements or respiration at birth, congenital contractures, and early death; see AMC6 (<a href="/entry/619334">619334</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10619714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Romero, N. B., Lehtokari, V.-L., Quijano-Roy, S., Monnier, N., Claeys, K. G., Carlier, R. Y., Pellegrini, N., Orlikowski, D., Barois, A., Laing, N. G., Lunardi, J., Fardeau, N., Pelin, K., Wallgren-Pettersson, C. &lt;strong&gt;Core-rod myopathy caused by mutations in the nebulin gene.&lt;/strong&gt; Neurology 73: 1159-1161, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19805734/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19805734&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181bacf45&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19805734">Romero et al. (2009)</a> reported a 27-year-old man with NEM2 confirmed by genetic analysis. He presented at birth with generalized hypotonia, poor spontaneous movements, and restrictive respiratory insufficiency requiring mechanical ventilation. He showed diffuse muscle weakness with axial predominance, never acquired independent ambulation, and developed multiple joint contractures. As an adult, he was quadriplegic with mild facial weakness. No cardiac symptoms were observed. Muscle biopsy showed numerous fibers with distinctive rods and well-delineated cores in type 1 fibers. Electron microscopy showed rods with characteristic striation and cores with some sarcomeric disorganization and depletion of mitochondria. The histologic findings indicated that cores, in addition to rods, may be found in patients with NEM2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19805734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, <a href="#15" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. &lt;strong&gt;Mutation update: the spectra of nebulin variants and associated myopathies.&lt;/strong&gt; Hum. Mutat. 35: 1418-1426, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25205138/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25205138&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25205138[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25205138">Lehtokari et al. (2014)</a> noted that the most common associated phenotype was nemaline myopathy (90% of families). Within this broad category, there was a range of severity. In addition, some families with NEB mutations had more diverse manifestations, including early-onset distal myopathy without nemaline bodies (4 families), a distal form of nemaline myopathy (3 families), core-rod myopathy with generalized muscle weakness (3 families), a childhood-onset distal myopathy with rods and cores (3 families), and fetal akinesia/lethal multiple pterygium syndrome (AMC6) (3 families). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" 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>Distal Myopathy</em></strong></p><p>
<a href="#35" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. &lt;strong&gt;Distal myopathy caused by homozygous missense mutations in the nebulin gene.&lt;/strong&gt; Brain 130: 1465-1476, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17525139/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17525139&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/awm094&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> reported 7 patients from 4 unrelated Finnish families with NEM2 presenting as distal myopathy with foot drop between the first and third decades after normal early motor development. Muscle weakness predominantly affected the ankle dorsiflexors, finger extensors, and neck flexors, resulting in walking difficulties and increased falls in some patients. The patients were unable to walk on their heels. Additional variable features included high-arched palate, slight facial weakness, dysarthria, pseudohypertrophy of the calves, and mild atrophy of proximal muscles of the upper and lower limbs. Radiographic imaging showed fatty replacement of the muscles of the anterior compartment of the lower legs. None of the patients had breathing problems or dysphagia, and serum creatine kinase was not elevated. Muscle biopsy showed myopathic changes with marked fiber size variability, fibrosis, and large hypertrophic fibers with increased internal nuclei. Rare nemaline rods or bodies were observed, although these were often apparent only on electron microscopy or with special staining. The patients were initially thought to have tibial muscular dystrophy (TMD; <a href="/entry/600334">600334</a>), but molecular analysis excluded that diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17525139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of NEM2 in the families reported by <a href="#15" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. &lt;strong&gt;Mutation update: the spectra of nebulin variants and associated myopathies.&lt;/strong&gt; Hum. Mutat. 35: 1418-1426, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25205138/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25205138&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25205138[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25205138">Lehtokari et al. (2014)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" 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="#33" class="mim-tip-reference" title="Wallgren-Pettersson, C., Avela, K., Marchand, S., Kolehmainen, J., Tahvanainen, E., Hansen, F. J., Muntoni, F., Dubowitz, V., de Visser, M., Van Langen, I. M., Laing, N. G., Faure, S., de la Chapelle, A. &lt;strong&gt;A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis.&lt;/strong&gt; Neuromusc. Disord. 5: 441-443, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8580725/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8580725&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0960-8966(95)00022-f&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8580725">Wallgren-Pettersson et al. (1995)</a> used genetic linkage analysis from 7 European families with autosomal recessive nemaline myopathy to map a candidate disease locus, designated NEM2, to a 13-cM region on chromosome 2q21.2-q22 between markers D2S150 and D2S142 (maximum lod score of 5.34 at marker D2S151). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8580725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By radiation hybrid mapping, <a href="#25" class="mim-tip-reference" title="Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. &lt;strong&gt;Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.&lt;/strong&gt; Europ. J. Hum. Genet. 5: 229-234, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9359044/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9359044&lt;/a&gt;]" pmid="9359044">Pelin et al. (1997)</a> mapped the nebulin gene to a position close to the microsatellite marker D2S2236 on 2q22. They also mapped the titin gene (<a href="/entry/188840">188840</a>) to the vicinity of markers D2S384 and D2S364 on 2q24.3. <a href="#25" class="mim-tip-reference" title="Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. &lt;strong&gt;Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.&lt;/strong&gt; Europ. J. Hum. Genet. 5: 229-234, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9359044/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9359044&lt;/a&gt;]" pmid="9359044">Pelin et al. (1997)</a> concluded that of these 2 giant muscle proteins, the gene for nebulin resides within the candidate region for NEM2, whereas the titin gene is located outside this region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9359044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<p>In patients with autosomal recessive typical nemaline myopathy-2 (NEM2), <a href="#24" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. &lt;strong&gt;Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.&lt;/strong&gt; Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10051637/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10051637&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.96.5.2305&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10051637">Pelin et al. (1999)</a> identified pathogenic mutations in the NEB gene (<a href="/entry/161650#0001">161650.0001</a>-<a href="/entry/161650#0006">161650.0006</a>). The mutations were frameshift, nonsense, and splice site. <a href="#34" class="mim-tip-reference" title="Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K. &lt;strong&gt;Mutations in the nebulin gene can cause severe congenital nemaline myopathy.&lt;/strong&gt; Neuromusc. Disord. 12: 674-679, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12207937/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12207937&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(02)00065-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12207937">Wallgren-Pettersson et al. (2002)</a> noted that the phenotype of 2 French sibs (family 3) reported by <a href="#24" class="mim-tip-reference" title="Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C. &lt;strong&gt;Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.&lt;/strong&gt; Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10051637/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10051637&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.96.5.2305&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10051637">Pelin et al. (1999)</a> was more consistent with AMC6 than NEM2 (see <a href="/entry/161650#0003">161650.0003</a> and <a href="/entry/161650#0004">161650.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12207937+10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy, <a href="#1" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. &lt;strong&gt;Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.&lt;/strong&gt; Hum. Genet. 115: 185-190, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15221447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15221447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-004-1140-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15221447">Anderson et al. (2004)</a> identified a 2,502-bp deletion in the NEB gene (<a href="/entry/161650#0007">161650.0007</a>), resulting in removal of exon 55. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using denaturing high-performance liquid chromatography (DHPLC), <a href="#16" class="mim-tip-reference" title="Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C. &lt;strong&gt;Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.&lt;/strong&gt; Hum. Mutat. 27: 946-956, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16917880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16917880&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20370&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16917880">Lehtokari et al. (2006)</a> identified 45 novel mutations in the NEB gene in affected members of 44 unrelated families with nemaline myopathy. Mutations were identified in patients representing all clinical categories of disease severity. The majority (55%) of mutations were frameshift or nonsense mutations resulting in premature termination of the protein. Mutations were distributed throughout the gene, with no obvious hotspots. <a href="#16" class="mim-tip-reference" title="Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C. &lt;strong&gt;Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.&lt;/strong&gt; Hum. Mutat. 27: 946-956, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16917880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16917880&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20370&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16917880">Lehtokari et al. (2006)</a> concluded that mutations in the NEB gene are the most common cause of nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 patients from 4 unrelated Finnish families, 2 of whom were consanguineous, with NEM2 manifest as distal myopathy with onset in childhood or adulthood, <a href="#35" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. &lt;strong&gt;Distal myopathy caused by homozygous missense mutations in the nebulin gene.&lt;/strong&gt; Brain 130: 1465-1476, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17525139/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17525139&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/awm094&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> identified homozygous missense mutations in the NEB gene (T5681P, <a href="/entry/161650#0008">161650.0008</a> and S4665I, <a href="/entry/161650#0009">161650.0009</a>). The mutations segregated with the disorder in the families from whom DNA was available. Functional studies of the mutation were not performed, but <a href="#35" class="mim-tip-reference" title="Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B. &lt;strong&gt;Distal myopathy caused by homozygous missense mutations in the nebulin gene.&lt;/strong&gt; Brain 130: 1465-1476, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17525139/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17525139&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/awm094&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17525139">Wallgren-Pettersson et al. (2007)</a> noted that both missense mutations had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more severe typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17525139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, <a href="#15" class="mim-tip-reference" title="Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C. &lt;strong&gt;Mutation update: the spectra of nebulin variants and associated myopathies.&lt;/strong&gt; Hum. Mutat. 35: 1418-1426, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25205138/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25205138&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25205138[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25205138">Lehtokari et al. (2014)</a> found that the most common types of mutations were splice-site mutations (34%), followed by frameshift (32%), nonsense (23%), and finally missense (7%). The vast majority of patients had compound heterozygous mutations. There were no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25205138" 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>Associations Pending Confirmation</em></strong></p><p>
For discussion of a possible association between nemaline myopathy and variation in the RYR3 gene, see <a href="/entry/180903#0001">180903.0001</a> and <a href="/entry/180903#0002">180903.0002</a>.</p>
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<p><a href="#22" class="mim-tip-reference" title="Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H. &lt;strong&gt;Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.&lt;/strong&gt; Hum. Molec. Genet. 18: 2359-2369, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19346529/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19346529&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp168&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19346529">Ottenheijm et al. (2009)</a> studied the muscular phenotype of nemaline myopathy (NM) patients with a well-defined nebulin mutation (NM-NEB), resulting in deletion of exon 55 from the transcript (<a href="/entry/161650#0007">161650.0007</a>). SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. <a href="#22" class="mim-tip-reference" title="Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H. &lt;strong&gt;Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.&lt;/strong&gt; Hum. Molec. Genet. 18: 2359-2369, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19346529/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19346529&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp168&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19346529">Ottenheijm et al. (2009)</a> hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19346529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. &lt;strong&gt;Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.&lt;/strong&gt; Hum. Genet. 115: 185-190, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15221447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15221447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-004-1140-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15221447">Anderson et al. (2004)</a> screened for 2,503-bp deletion (ex55 del) in a random sample of 4,090 Ashkenazi Jewish individuals, revealing a carrier frequency of 1 in 108. <a href="#14" class="mim-tip-reference" title="Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C. &lt;strong&gt;The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.&lt;/strong&gt; Neuromusc. Disord. 19: 179-181, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19232495/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19232495&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.12.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19232495">Lehtokari et al. (2009)</a> identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by <a href="#1" class="mim-tip-reference" title="Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y. &lt;strong&gt;Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.&lt;/strong&gt; Hum. Genet. 115: 185-190, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15221447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15221447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-004-1140-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15221447">Anderson et al. (2004)</a>. Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15221447+19232495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The condition described by <a href="#8" class="mim-tip-reference" title="Gibson, A. &lt;strong&gt;Muscular infantilism.&lt;/strong&gt; Arch. Intern. Med. 27: 338-350, 1921."None>Gibson (1921)</a> as 'muscular infantilism' in a family spanning 3 generations may have been nemaline myopathy.</p><p><a href="#31" class="mim-tip-reference" title="Shy, G. M., Engel, W. K., Somers, J. E., Wanko, T. &lt;strong&gt;Nemaline Myopathy: a new congenital myopathy.&lt;/strong&gt; Brain 86: 793-810, 1963.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14090530/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14090530&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/86.4.793&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14090530">Shy et al. (1963)</a> reported a slowly progressive 'new congenital myopathy' in 2 sibs. One patient was a 4-year-old girl. Muscle biopsy showed subsarcolemmal aggregates of abnormal rod-shaped or thread-like structures. Electron microscopy showed that the rod-like bodies were composed of abnormal fibrillar material. The parents showed minor abnormalities, which were interpreted as possible heterozygous effects. At the same time, <a href="#3" class="mim-tip-reference" title="Conen, P. E., Murphy, E. G., Donohue, W. L. &lt;strong&gt;Light and electron microscopic studies of &quot;myogranules&quot; in a child with hypotonia and muscle weakness.&lt;/strong&gt; Can. Med. Assoc. J. 89: 983-986, 1963.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14076166/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14076166&lt;/a&gt;]" pmid="14076166">Conen et al. (1963)</a> reported a child with hypotonia and muscle weakness who had 'myogranules' on skeletal muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14090530+14076166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The mother and daughter described by <a href="#7" class="mim-tip-reference" title="Ford, F. R. &lt;strong&gt;Diseases of the Nervous System in Infancy, Childhood and Adolescence. (4th ed.).&lt;/strong&gt; Springfield, Ill.: Charles C Thomas (pub.) 1961. Pp. 1259-1260."None>Ford (1961)</a> as cases of 'congenital universal muscular hypoplasia of Krabbe' (<a href="/entry/159100">159100</a>) were shown by <a href="#11" class="mim-tip-reference" title="Hopkins, I. J., Lindsey, J. R., Ford, F. R. &lt;strong&gt;Nemaline myopathy. A long-term clinicopathologic study of affected mother and daughter.&lt;/strong&gt; Brain 89: 299-310, 1966.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5939042/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5939042&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/89.2.299&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5939042">Hopkins et al. (1966)</a> to have nemaline myopathy. <a href="#5" class="mim-tip-reference" title="Engel, W. K., Wanko, T., Fenichel, G. M. &lt;strong&gt;Nemaline myopathy; a second case.&lt;/strong&gt; Arch. Neurol. 11: 22-39, 1964.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14147679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14147679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1964.00460190026003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14147679">Engel et al. (1964)</a> reported a 16-year-old girl with nemaline myopathy and suggested that she had slow progression of the disease through late childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14147679+5939042" 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="#26" class="mim-tip-reference" title="Price, H. M., Gordon, G. B., Pearson, C. M., Munsat, T. L., Blumberg, J. M. &lt;strong&gt;New evidence for excessive accumulation of Z-band material in nemaline myopathy.&lt;/strong&gt; Proc. Nat. Acad. Sci. 54: 1398-1406, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5218258/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5218258&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.54.5.1398&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5218258">Price et al. (1965)</a> reported 3 cases. An 8.5-year-old white girl had generalized muscle weakness and hypotonia since birth. She walked with difficulty at age 17 months, and had difficulty arising from the floor. Her face was elongated, with decreased expression and a high-arched palate. She had proximal girdle muscle weakness and hypo- or areflexia. Two sibs were similarly affected. Two African American girls, aged 11 and 12 years, had diffuse muscle weakness from birth. Motor milestones were delayed. Both girls had elongated, dysmorphic, expressionless facies, jaw weakness, and very high-arched palate. One child was limited to a wheelchair, and the other walked only with great difficulty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5218258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Pearson, C. M., Coleman, R. F., Fowler, W. M., Mommaerts, W. F., Munsat, T. L., Peter, J. B. &lt;strong&gt;Skeletal muscle. Basic and clinical aspects and illustrative new diseases.&lt;/strong&gt; Ann. Intern. Med. 67: 614-650, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5342815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5342815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.7326/0003-4819-67-3-614&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5342815">Pearson et al. (1967)</a> described 3 affected sibs out of 8. The mother, although clinically normal, had minor histologic alterations of skeletal muscle. In 3 affected brothers born of unaffected parents, <a href="#4" class="mim-tip-reference" title="Danowski, T. S., Fisher, E. R., Wald, N., Wester, J. W., Zawadzki, Z. A. &lt;strong&gt;Rod myopathy: beta globulin peak and increased complement.&lt;/strong&gt; Metabolism 22: 597-604, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4121348/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4121348&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0026-0495(73)90073-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4121348">Danowski et al. (1973)</a> found a distinct beta globulin peak upon serum protein electrophoresis. This sharp beta peak was caused by an increase in the C3 component of serum complement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4121348+5342815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Jenis, E. H., Lindquist, R. R., Lister, R. C. &lt;strong&gt;New congenital myopathy with crystalline intranuclear inclusions.&lt;/strong&gt; Arch. Neurol. 20: 281-287, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5766493/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5766493&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1969.00480090069011&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5766493">Jenis et al. (1969)</a> described a white girl, born of unrelated parents, who showed extreme muscular weakness and hypotonia from birth and died of respiratory insufficiency at 2 months of age. Intranuclear and sarcoplasmic rod inclusions were found in muscle cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5766493" 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>Meier et al. (<a href="#19" class="mim-tip-reference" title="Meier, C., Gertsch, M., Zimmerman, A., Voellmy, W., Geissbuhler, J. &lt;strong&gt;Nemaline myopathy presenting as cardiomyopathy. (Letter)&lt;/strong&gt; New Eng. J. Med. 308: 1536-1537, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6855830/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6855830&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/nejm198306233082515&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6855830">1983</a>, <a href="#20" class="mim-tip-reference" title="Meier, C., Voellmy, W., Gertsch, M., Zimmermann, A., Geissbuhler, J. &lt;strong&gt;Nemaline myopathy appearing in adults as cardiomyopathy: a clinicopathologic study.&lt;/strong&gt; Arch. Neurol. 41: 443-445, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6703949/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6703949&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1984.04050160109025&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6703949">1984</a>) described nemaline myopathy as the cause of fatal cardiomyopathy in a 29-year-old woman. She had a leptosomal habitus but no neuromuscular abnormalities. Quadriceps biopsy showed type 1 fiber predominance and nemaline rods in about 50% of muscle fibers by trichrome staining and electron microscopy. Autopsy showed nemaline bodies in the myocardium, including the conducting tissue. The patient's mother and 1 of her sisters suffered sudden unexplained death at ages 47 and 37, respectively; sections of the sister's myocardium showed nemaline bodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6703949+6855830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Arts, W. F., Bethlem, J., Dingemans, K. P., Eriksson, A. W. &lt;strong&gt;Investigations on the inheritance of nemaline myopathy.&lt;/strong&gt; Arch. Neurol. 35: 72-77, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/623532/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;623532&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1978.00500260010002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="623532">Arts et al. (1978)</a> suggested the existence of both dominant and recessive forms of nemaline or rod myopathy. The 2 forms could not be distinguished on clinical or histopathologic grounds. The authors found in 2 families that both parents of each index patient had rods and an increased number of fibers with central nuclei, a presumed heterozygous manifestation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=623532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Kondo, K., Yuasa, T. &lt;strong&gt;Genetics of congenital nemaline myopathy.&lt;/strong&gt; Muscle Nerve 3: 308-315, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6997732/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6997732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mus.880030407&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6997732">Kondo and Yuasa (1980)</a> reviewed all reported cases of congenital nemaline myopathy and concluded that autosomal dominant inheritance was the only acceptable genetic hypothesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6997732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="McMenamin, J. B., Curry, B., Taylor, G. P., Becker, L. E., Murphy, E. G. &lt;strong&gt;Fatal nemaline myopathy in infancy.&lt;/strong&gt; Can. J. Neurol. Sci. 11: 305-309, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6733612/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6733612&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1017/s0317167100045583&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6733612">McMenamin et al. (1984)</a> reported 2 infants with fatal nemaline myopathy. One presented at birth with severe hypotonia, respiratory failure, and contractures, and died shortly after the neonatal period. The other patient presented at age 2 months with hypotonia, and died of respiratory failure at age 7 months. Pathologic findings in both cases showed numerous rod bodies in the diaphragm and limb muscles. No abnormalities were seen in the central or peripheral nervous systems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6733612" 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="#29" class="mim-tip-reference" title="Schmalbruch, H., Kamieniecka, Z., Arroe, M. &lt;strong&gt;Early fatal nemaline myopathy: case report and review.&lt;/strong&gt; Dev. Med. Child Neurol. 29: 800-804, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2826279/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2826279&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-8749.1987.tb08828.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2826279">Schmalbruch et al. (1987)</a> described the early fatal form of nemaline myopathy in 1 case and reviewed 13 reported cases. All died within the first year of life. Three affected sibs were reported by <a href="#21" class="mim-tip-reference" title="Neustein, H. B. &lt;strong&gt;Nemaline myopathy: a family study with three autopsied cases.&lt;/strong&gt; Arch. Path. 96: 192-195, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4124693/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4124693&lt;/a&gt;]" pmid="4124693">Neustein (1973)</a> and 2 affected sibs were reported by <a href="#9" class="mim-tip-reference" title="Gillies, C., Raye, J., Vasan, U., Hart, W. E., Goldblatt, P. J. &lt;strong&gt;Nemaline rod myopathy: a possible cause of rapidly fatal infantile hypotonia.&lt;/strong&gt; Arch. Path. Lab. Med. 103: 1-5, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/581546/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;581546&lt;/a&gt;]" pmid="581546">Gillies et al. (1979)</a>. <a href="#10" class="mim-tip-reference" title="Harati, Y., Niakan, E., Bloom, K., Casar, G. &lt;strong&gt;Adult onset of nemaline myopathy presenting as diaphragmatic paralysis.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 50: 108-110, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3819745/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3819745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.50.1.108&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3819745">Harati et al. (1987)</a> reported a case of nemaline myopathy presenting in adulthood as diaphragmatic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2826279+4124693+3819745+581546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Harati, Y., Niakan, E., Bloom, K., Casar, G. &lt;strong&gt;Adult onset of nemaline myopathy presenting as diaphragmatic paralysis.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 50: 108-110, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3819745/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3819745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.50.1.108&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3819745">Harati et al. (1987)</a> reported a case of nemaline myopathy presenting in adulthood as diaphragmatic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3819745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Wallgren-Pettersson, C. &lt;strong&gt;Congenital nemaline myopathy: a clinical follow-up study of twelve patients.&lt;/strong&gt; J. Neurol. Sci. 89: 1-14, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2926439/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2926439&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(89)90002-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2926439">Wallgren-Pettersson (1989)</a> reported follow-up of 12 patients with congenital nemaline myopathy. Ten showed clinical deterioration and 2 showed improvement. Muscle weakness was most severe in the facial muscles, flexors of the neck and trunk, dorsiflexors of the feet, and extensors of the toes. Distal limb muscles and limb-girdle muscles were more severely affected than proximal limb muscles. There were no signs of central nervous system involvement. Prognosis was influenced mainly by the presence of scoliosis and restricted respiratory capacity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2926439" 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="#17" class="mim-tip-reference" title="Maayan, C., Springer, C., Armon, Y., Bar-Yishay, E., Shapira, Y., Godfrey, S. &lt;strong&gt;Nemaline myopathy as a cause of sleep hypoventilation.&lt;/strong&gt; Pediatrics 77: 390-395, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3081871/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3081871&lt;/a&gt;]" pmid="3081871">Maayan et al. (1986)</a> described sleep hypoventilation in a brother and sister, aged 14.5 and 11.5 years, respectively, with nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3081871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Falga-Tirado, C., Perez-Peman, P., Ordi-Ros, J., Bofill, J. M., Balcells, E. &lt;strong&gt;Adult onset of nemaline myopathy presenting as respiratory insufficiency.&lt;/strong&gt; Respiration 62: 353-354, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8552868/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8552868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000196479&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8552868">Falga-Tirado et al. (1995)</a> reported a case of adult-onset nemaline myopathy presenting as respiratory insufficiency without generalized muscle weakness. Serum muscle enzymes were normal, but biceps muscle biopsy showed abundant nemaline bodies. Diaphragmatic movement appeared to be normal by ultrasound of the chest and esophageal tonometry. The patient was successfully treated with nasal intermittent pressure ventilation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8552868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Vendittelli, F., Manciet-Labarchede, C., Gilbert-Dussardier, B. &lt;strong&gt;Nemaline myopathy in the neonate: two case reports.&lt;/strong&gt; Europ. J. Pediat. 155: 502-505, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8789770/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8789770&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01955190&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8789770">Vendittelli et al. (1996)</a> described a severe form of nemaline myopathy associated with early death in the neonate. Decreased fetal movement was noted during pregnancy in each case. One infant was born with joint contractures of the hands and feet, severe hypotonia, and edema of the hands and feet. Chest radiographs showed lung hypoplasia, thin ribs, and an elevated diaphragm. He died at the age of 6 days from respiratory failure. The second patient, a girl, was born from a pregnancy characterized by hydramnios hand persistent breech presentation. She showed respiratory failure, hypotonia, and inability to swallow, and died from respiratory failure at the age of 68 days. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8789770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Animal Model</strong>
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<p>In a review, <a href="#30" class="mim-tip-reference" title="Shelton, G. D., Engvall, E. &lt;strong&gt;Canine and feline models of human inherited muscle diseases.&lt;/strong&gt; Neuromusc. Disord. 15: 127-138, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15694134/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15694134&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2004.10.019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15694134">Shelton and Engvall (2005)</a> stated that models of nemaline rod myopathy had been described in Border Collie and Schipperke dogs and a family of cats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15694134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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<ol>
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<a id="1" class="mim-anchor"></a>
<a id="Anderson2004" class="mim-anchor"></a>
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<p class="mim-text-font">
Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y.
<strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong>
Hum. Genet. 115: 185-190, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s00439-004-1140-8" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Arts1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Arts, W. F., Bethlem, J., Dingemans, K. P., Eriksson, A. W.
<strong>Investigations on the inheritance of nemaline myopathy.</strong>
Arch. Neurol. 35: 72-77, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/623532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">623532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=623532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1978.00500260010002" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
<a id="Conen1963" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Conen, P. E., Murphy, E. G., Donohue, W. L.
<strong>Light and electron microscopic studies of "myogranules" in a child with hypotonia and muscle weakness.</strong>
Can. Med. Assoc. J. 89: 983-986, 1963.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14076166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14076166</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14076166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Danowski1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danowski, T. S., Fisher, E. R., Wald, N., Wester, J. W., Zawadzki, Z. A.
<strong>Rod myopathy: beta globulin peak and increased complement.</strong>
Metabolism 22: 597-604, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4121348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4121348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4121348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0026-0495(73)90073-5" target="_blank">Full Text</a>]
</p>
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<li>
<a id="5" class="mim-anchor"></a>
<a id="Engel1964" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Engel, W. K., Wanko, T., Fenichel, G. M.
<strong>Nemaline myopathy; a second case.</strong>
Arch. Neurol. 11: 22-39, 1964.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14147679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14147679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14147679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1964.00460190026003" target="_blank">Full Text</a>]
</p>
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</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Falga-Tirado1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Falga-Tirado, C., Perez-Peman, P., Ordi-Ros, J., Bofill, J. M., Balcells, E.
<strong>Adult onset of nemaline myopathy presenting as respiratory insufficiency.</strong>
Respiration 62: 353-354, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8552868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8552868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8552868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000196479" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="Ford1961" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ford, F. R.
<strong>Diseases of the Nervous System in Infancy, Childhood and Adolescence. (4th ed.).</strong>
Springfield, Ill.: Charles C Thomas (pub.) 1961. Pp. 1259-1260.
</p>
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<a id="8" class="mim-anchor"></a>
<a id="Gibson1921" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibson, A.
<strong>Muscular infantilism.</strong>
Arch. Intern. Med. 27: 338-350, 1921.
</p>
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</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Gillies1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gillies, C., Raye, J., Vasan, U., Hart, W. E., Goldblatt, P. J.
<strong>Nemaline rod myopathy: a possible cause of rapidly fatal infantile hypotonia.</strong>
Arch. Path. Lab. Med. 103: 1-5, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/581546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">581546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=581546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="10" class="mim-anchor"></a>
<a id="Harati1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Harati, Y., Niakan, E., Bloom, K., Casar, G.
<strong>Adult onset of nemaline myopathy presenting as diaphragmatic paralysis.</strong>
J. Neurol. Neurosurg. Psychiat. 50: 108-110, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3819745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3819745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3819745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jnnp.50.1.108" target="_blank">Full Text</a>]
</p>
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<a id="11" class="mim-anchor"></a>
<a id="Hopkins1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hopkins, I. J., Lindsey, J. R., Ford, F. R.
<strong>Nemaline myopathy. A long-term clinicopathologic study of affected mother and daughter.</strong>
Brain 89: 299-310, 1966.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5939042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5939042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5939042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/89.2.299" target="_blank">Full Text</a>]
</p>
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<li>
<a id="12" class="mim-anchor"></a>
<a id="Jenis1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jenis, E. H., Lindquist, R. R., Lister, R. C.
<strong>New congenital myopathy with crystalline intranuclear inclusions.</strong>
Arch. Neurol. 20: 281-287, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5766493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5766493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5766493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1969.00480090069011" target="_blank">Full Text</a>]
</p>
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<a id="13" class="mim-anchor"></a>
<a id="Kondo1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kondo, K., Yuasa, T.
<strong>Genetics of congenital nemaline myopathy.</strong>
Muscle Nerve 3: 308-315, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6997732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6997732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6997732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/mus.880030407" target="_blank">Full Text</a>]
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<a id="Lehtokari2009" class="mim-anchor"></a>
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<p class="mim-text-font">
Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C.
<strong>The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.</strong>
Neuromusc. Disord. 19: 179-181, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19232495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19232495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19232495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.nmd.2008.12.001" target="_blank">Full Text</a>]
</p>
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<a id="15" class="mim-anchor"></a>
<a id="Lehtokari2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C.
<strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong>
Hum. Mutat. 35: 1418-1426, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25205138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25205138</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25205138[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=25205138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.22693" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
<a id="Lehtokari2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C.
<strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
Hum. Mutat. 27: 946-956, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917880</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.20370" target="_blank">Full Text</a>]
</p>
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<a id="17" class="mim-anchor"></a>
<a id="Maayan1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maayan, C., Springer, C., Armon, Y., Bar-Yishay, E., Shapira, Y., Godfrey, S.
<strong>Nemaline myopathy as a cause of sleep hypoventilation.</strong>
Pediatrics 77: 390-395, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3081871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3081871</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3081871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="18" class="mim-anchor"></a>
<a id="McMenamin1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McMenamin, J. B., Curry, B., Taylor, G. P., Becker, L. E., Murphy, E. G.
<strong>Fatal nemaline myopathy in infancy.</strong>
Can. J. Neurol. Sci. 11: 305-309, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6733612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6733612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6733612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1017/s0317167100045583" target="_blank">Full Text</a>]
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<a id="Meier1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Meier, C., Gertsch, M., Zimmerman, A., Voellmy, W., Geissbuhler, J.
<strong>Nemaline myopathy presenting as cardiomyopathy. (Letter)</strong>
New Eng. J. Med. 308: 1536-1537, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6855830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6855830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6855830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/nejm198306233082515" target="_blank">Full Text</a>]
</p>
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<a id="20" class="mim-anchor"></a>
<a id="Meier1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Meier, C., Voellmy, W., Gertsch, M., Zimmermann, A., Geissbuhler, J.
<strong>Nemaline myopathy appearing in adults as cardiomyopathy: a clinicopathologic study.</strong>
Arch. Neurol. 41: 443-445, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6703949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6703949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6703949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1984.04050160109025" target="_blank">Full Text</a>]
</p>
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<a id="21" class="mim-anchor"></a>
<a id="Neustein1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neustein, H. B.
<strong>Nemaline myopathy: a family study with three autopsied cases.</strong>
Arch. Path. 96: 192-195, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4124693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4124693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4124693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
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<li>
<a id="22" class="mim-anchor"></a>
<a id="Ottenheijm2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H.
<strong>Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.</strong>
Hum. Molec. Genet. 18: 2359-2369, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19346529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19346529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19346529[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=19346529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddp168" target="_blank">Full Text</a>]
</p>
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<a id="23" class="mim-anchor"></a>
<a id="Pearson1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pearson, C. M., Coleman, R. F., Fowler, W. M., Mommaerts, W. F., Munsat, T. L., Peter, J. B.
<strong>Skeletal muscle. Basic and clinical aspects and illustrative new diseases.</strong>
Ann. Intern. Med. 67: 614-650, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5342815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5342815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5342815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.7326/0003-4819-67-3-614" target="_blank">Full Text</a>]
</p>
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<a id="Pelin1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
<strong>Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
Proc. Nat. Acad. Sci. 96: 2305-2310, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051637[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=10051637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.96.5.2305" target="_blank">Full Text</a>]
</p>
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<a id="Pelin1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
<strong>Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.</strong>
Europ. J. Hum. Genet. 5: 229-234, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9359044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9359044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9359044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<li>
<a id="26" class="mim-anchor"></a>
<a id="Price1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Price, H. M., Gordon, G. B., Pearson, C. M., Munsat, T. L., Blumberg, J. M.
<strong>New evidence for excessive accumulation of Z-band material in nemaline myopathy.</strong>
Proc. Nat. Acad. Sci. 54: 1398-1406, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5218258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5218258</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5218258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.54.5.1398" target="_blank">Full Text</a>]
</p>
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<a id="Romero2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Romero, N. B., Lehtokari, V.-L., Quijano-Roy, S., Monnier, N., Claeys, K. G., Carlier, R. Y., Pellegrini, N., Orlikowski, D., Barois, A., Laing, N. G., Lunardi, J., Fardeau, N., Pelin, K., Wallgren-Pettersson, C.
<strong>Core-rod myopathy caused by mutations in the nebulin gene.</strong>
Neurology 73: 1159-1161, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805734</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19805734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e3181bacf45" target="_blank">Full Text</a>]
</p>
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<a id="Sanoudou2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sanoudou, D., Beggs, A. H.
<strong>Clinical and genetic heterogeneity in nemaline myopathy--a disease of skeletal muscle thin filaments.</strong>
Trends Molec. Med. 7: 362-368, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11516997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11516997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11516997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s1471-4914(01)02089-5" target="_blank">Full Text</a>]
</p>
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<a id="29" class="mim-anchor"></a>
<a id="Schmalbruch1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schmalbruch, H., Kamieniecka, Z., Arroe, M.
<strong>Early fatal nemaline myopathy: case report and review.</strong>
Dev. Med. Child Neurol. 29: 800-804, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2826279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2826279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2826279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1469-8749.1987.tb08828.x" target="_blank">Full Text</a>]
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<a id="Shelton2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shelton, G. D., Engvall, E.
<strong>Canine and feline models of human inherited muscle diseases.</strong>
Neuromusc. Disord. 15: 127-138, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15694134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15694134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15694134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.nmd.2004.10.019" target="_blank">Full Text</a>]
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<a id="Shy1963" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shy, G. M., Engel, W. K., Somers, J. E., Wanko, T.
<strong>Nemaline Myopathy: a new congenital myopathy.</strong>
Brain 86: 793-810, 1963.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14090530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14090530</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14090530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/86.4.793" target="_blank">Full Text</a>]
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<a id="Vendittelli1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Vendittelli, F., Manciet-Labarchede, C., Gilbert-Dussardier, B.
<strong>Nemaline myopathy in the neonate: two case reports.</strong>
Europ. J. Pediat. 155: 502-505, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8789770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8789770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8789770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01955190" target="_blank">Full Text</a>]
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<a id="Wallgren-Pettersson1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wallgren-Pettersson, C., Avela, K., Marchand, S., Kolehmainen, J., Tahvanainen, E., Hansen, F. J., Muntoni, F., Dubowitz, V., de Visser, M., Van Langen, I. M., Laing, N. G., Faure, S., de la Chapelle, A.
<strong>A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis.</strong>
Neuromusc. Disord. 5: 441-443, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8580725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8580725</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8580725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0960-8966(95)00022-f" target="_blank">Full Text</a>]
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<a id="Wallgren-Pettersson2002" class="mim-anchor"></a>
<div class="">
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Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K.
<strong>Mutations in the nebulin gene can cause severe congenital nemaline myopathy.</strong>
Neuromusc. Disord. 12: 674-679, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12207937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12207937</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12207937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0960-8966(02)00065-2" target="_blank">Full Text</a>]
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<a id="Wallgren-Pettersson2007" class="mim-anchor"></a>
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Wallgren-Pettersson, C., Lehtokari, V.-L., Kalimo, H., Paetau, A., Nuutinen, E., Hackman, P., Sewry, C., Pelin, K., Udd, B.
<strong>Distal myopathy caused by homozygous missense mutations in the nebulin gene.</strong>
Brain 130: 1465-1476, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17525139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17525139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17525139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/awm094" target="_blank">Full Text</a>]
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<a id="Wallgren-Pettersson1999" class="mim-anchor"></a>
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<p class="mim-text-font">
Wallgren-Pettersson, C., Pelin, K., Hilpela, P., Donner, K., Porfirio, B., Graziano, C., Swoboda, K. J., Fardeau, M., Urtizberea, J. A., Muntoni, F., Sewry, C., Dubowitz, V., and 10 others.
<strong>Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy.</strong>
Neuromusc. Disord. 9: 564-572, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10619714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10619714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10619714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0960-8966(99)00061-9" target="_blank">Full Text</a>]
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<a id="Wallgren-Pettersson1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wallgren-Pettersson, C.
<strong>Congenital nemaline myopathy: a clinical follow-up study of twelve patients.</strong>
J. Neurol. Sci. 89: 1-14, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2926439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2926439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2926439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(89)90002-6" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 05/21/2021
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Cassandra L. Kniffin - updated : 03/27/2018<br>Cassandra L. Kniffin - updated : 4/18/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 10/16/2009<br>Cassandra L. Kniffin - updated : 9/19/2006<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Cassandra L. Kniffin - updated : 4/4/2005<br>Victor A. McKusick - updated : 4/28/1999<br>Victor A. McKusick - updated : 10/30/1997<br>Orest Hurko - updated : 8/15/1995
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Victor A. McKusick : 6/4/1986
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<strong>#</strong> 256030
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NEMALINE MYOPATHY 2; NEM2
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<strong>ORPHA:</strong> 171430, 171433, 171436, 171439; &nbsp;
<strong>DO:</strong> 0110928; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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2q23.3
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Nemaline myopathy 2, autosomal recessive
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256030
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Autosomal recessive
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3
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NEB
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161650
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that nemaline myopathy-2 (NEM2) is caused by homozygous or compound heterozygous mutation in the nebulin gene (NEB; 161650) on chromosome 2q23.</p><p>Biallelic mutation in the NEB gene can also cause arthrogryposis multiplex congenita-6 (AMC6; 619334), which is much more severe and usually results in early death.</p>
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<strong>Description</strong>
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<p>Nemaline myopathy-2 (NEM2) is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by Lehtokari et al., 2014). </p><p><strong><em>Genetic Heterogeneity of Nemaline Myopathy</em></strong></p><p>
See also NEM1 (255310), caused by mutation in the tropomyosin-3 gene (TPM3; 191030) on chromosome 1q21; NEM3 (161800), caused by mutation in the alpha-actin-1 gene (ACTA1; 102610) on chromosome 1q42; NEM4 (609285), caused by mutation in the beta-tropomyosin gene (TPM2; 190990) on chromosome 9p13; NEM5A (605355), also known as Amish nemaline myopathy, NEM5B (620386), and NEM5C (620389), all caused by mutation in the troponin T1 gene (TNNT1; 191041) on chromosome 19q13; NEM6 (609273), caused by mutation in the KBTBD13 gene (613727) on chromosome 15q22; NEM7 (610687), caused by mutation in the cofilin-2 gene (CFL2; 601443) on chromosome 14q13; NEM8 (615348), caused by mutation in the KLHL40 gene (615340), on chromosome 3p22; NEM9 (615731), caused by mutation in the KLHL41 gene (607701) on chromosome 2q31; NEM10 (616165), caused by mutation in the LMOD3 gene (616112) on chromosome 3p14; and NEM11 (617336), caused by mutation in the MYPN gene (608517) on chromosome 10q21. Several of the genes encode components of skeletal muscle sarcomeric thin filaments (Sanoudou and Beggs, 2001). </p><p>Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006). </p>
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<strong>Clinical Features</strong>
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<p>Wallgren-Pettersson et al. (1999) reported 41 unrelated families with NEM2 suggested by linkage analysis. All were consistent with autosomal recessive inheritance. Wallgren-Pettersson et al. (1999) noted that phenotypic classification of nemaline myopathy is difficult because the disease spectrum forms a continuum; however, the authors described 2 main forms associated with NEB mutations: 'typical,' consistent with NEM2, and 'severe,' consistent with AMC6. Typical patients had generalized hypotonia at birth, with particular involvement of the bulbar, neck flexor, and respiratory muscles. Proximal limb muscles were weaker initially, but distal limb muscle weakness eventually occurred. The extraocular muscles were spared. The facies was myopathic with a high-arched palate. The spine was hyperlordotic, sometimes rigid, and scoliosis sometimes developed at puberty. Deep tendon reflexes were decreased or absent, and the gag reflex was often absent. Chest deformities were common, but there was no cardiac involvement. Imaging showed decreased muscle density with increased fatty infiltration. Serum creatine kinase was normal or mildly elevated. Muscle biopsies characteristically showed nemaline bodies and type 1 fiber predominance. Although myopathic changes were observed, there were no dystrophic or inflammatory changes. Despite delayed motor development and waddling gait, many patients with typical disease remained ambulatory as adults. Intelligence was normal. A subset of patients had severe disease characterized by absence of spontaneous movements or respiration at birth, congenital contractures, and early death; see AMC6 (619334). </p><p>Romero et al. (2009) reported a 27-year-old man with NEM2 confirmed by genetic analysis. He presented at birth with generalized hypotonia, poor spontaneous movements, and restrictive respiratory insufficiency requiring mechanical ventilation. He showed diffuse muscle weakness with axial predominance, never acquired independent ambulation, and developed multiple joint contractures. As an adult, he was quadriplegic with mild facial weakness. No cardiac symptoms were observed. Muscle biopsy showed numerous fibers with distinctive rods and well-delineated cores in type 1 fibers. Electron microscopy showed rods with characteristic striation and cores with some sarcomeric disorganization and depletion of mitochondria. The histologic findings indicated that cores, in addition to rods, may be found in patients with NEM2. </p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, Lehtokari et al. (2014) noted that the most common associated phenotype was nemaline myopathy (90% of families). Within this broad category, there was a range of severity. In addition, some families with NEB mutations had more diverse manifestations, including early-onset distal myopathy without nemaline bodies (4 families), a distal form of nemaline myopathy (3 families), core-rod myopathy with generalized muscle weakness (3 families), a childhood-onset distal myopathy with rods and cores (3 families), and fetal akinesia/lethal multiple pterygium syndrome (AMC6) (3 families). </p><p><strong><em>Distal Myopathy</em></strong></p><p>
Wallgren-Pettersson et al. (2007) reported 7 patients from 4 unrelated Finnish families with NEM2 presenting as distal myopathy with foot drop between the first and third decades after normal early motor development. Muscle weakness predominantly affected the ankle dorsiflexors, finger extensors, and neck flexors, resulting in walking difficulties and increased falls in some patients. The patients were unable to walk on their heels. Additional variable features included high-arched palate, slight facial weakness, dysarthria, pseudohypertrophy of the calves, and mild atrophy of proximal muscles of the upper and lower limbs. Radiographic imaging showed fatty replacement of the muscles of the anterior compartment of the lower legs. None of the patients had breathing problems or dysphagia, and serum creatine kinase was not elevated. Muscle biopsy showed myopathic changes with marked fiber size variability, fibrosis, and large hypertrophic fibers with increased internal nuclei. Rare nemaline rods or bodies were observed, although these were often apparent only on electron microscopy or with special staining. The patients were initially thought to have tibial muscular dystrophy (TMD; 600334), but molecular analysis excluded that diagnosis. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of NEM2 in the families reported by Lehtokari et al. (2014) was consistent with autosomal recessive inheritance. </p>
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<strong>Mapping</strong>
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<p>Wallgren-Pettersson et al. (1995) used genetic linkage analysis from 7 European families with autosomal recessive nemaline myopathy to map a candidate disease locus, designated NEM2, to a 13-cM region on chromosome 2q21.2-q22 between markers D2S150 and D2S142 (maximum lod score of 5.34 at marker D2S151). </p><p>By radiation hybrid mapping, Pelin et al. (1997) mapped the nebulin gene to a position close to the microsatellite marker D2S2236 on 2q22. They also mapped the titin gene (188840) to the vicinity of markers D2S384 and D2S364 on 2q24.3. Pelin et al. (1997) concluded that of these 2 giant muscle proteins, the gene for nebulin resides within the candidate region for NEM2, whereas the titin gene is located outside this region. </p>
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<strong>Molecular Genetics</strong>
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<p>In patients with autosomal recessive typical nemaline myopathy-2 (NEM2), Pelin et al. (1999) identified pathogenic mutations in the NEB gene (161650.0001-161650.0006). The mutations were frameshift, nonsense, and splice site. Wallgren-Pettersson et al. (2002) noted that the phenotype of 2 French sibs (family 3) reported by Pelin et al. (1999) was more consistent with AMC6 than NEM2 (see 161650.0003 and 161650.0004). </p><p>In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy, Anderson et al. (2004) identified a 2,502-bp deletion in the NEB gene (161650.0007), resulting in removal of exon 55. </p><p>Using denaturing high-performance liquid chromatography (DHPLC), Lehtokari et al. (2006) identified 45 novel mutations in the NEB gene in affected members of 44 unrelated families with nemaline myopathy. Mutations were identified in patients representing all clinical categories of disease severity. The majority (55%) of mutations were frameshift or nonsense mutations resulting in premature termination of the protein. Mutations were distributed throughout the gene, with no obvious hotspots. Lehtokari et al. (2006) concluded that mutations in the NEB gene are the most common cause of nemaline myopathy. </p><p>In 7 patients from 4 unrelated Finnish families, 2 of whom were consanguineous, with NEM2 manifest as distal myopathy with onset in childhood or adulthood, Wallgren-Pettersson et al. (2007) identified homozygous missense mutations in the NEB gene (T5681P, 161650.0008 and S4665I, 161650.0009). The mutations segregated with the disorder in the families from whom DNA was available. Functional studies of the mutation were not performed, but Wallgren-Pettersson et al. (2007) noted that both missense mutations had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more severe typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype. </p><p>In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, Lehtokari et al. (2014) found that the most common types of mutations were splice-site mutations (34%), followed by frameshift (32%), nonsense (23%), and finally missense (7%). The vast majority of patients had compound heterozygous mutations. There were no apparent genotype/phenotype correlations. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
For discussion of a possible association between nemaline myopathy and variation in the RYR3 gene, see 180903.0001 and 180903.0002.</p>
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<strong>Pathogenesis</strong>
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<p>Ottenheijm et al. (2009) studied the muscular phenotype of nemaline myopathy (NM) patients with a well-defined nebulin mutation (NM-NEB), resulting in deletion of exon 55 from the transcript (161650.0007). SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. Ottenheijm et al. (2009) hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations. </p>
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<strong>Population Genetics</strong>
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<p>Anderson et al. (2004) screened for 2,503-bp deletion (ex55 del) in a random sample of 4,090 Ashkenazi Jewish individuals, revealing a carrier frequency of 1 in 108. Lehtokari et al. (2009) identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by Anderson et al. (2004). Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect. </p>
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<strong>History</strong>
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<p>The condition described by Gibson (1921) as 'muscular infantilism' in a family spanning 3 generations may have been nemaline myopathy.</p><p>Shy et al. (1963) reported a slowly progressive 'new congenital myopathy' in 2 sibs. One patient was a 4-year-old girl. Muscle biopsy showed subsarcolemmal aggregates of abnormal rod-shaped or thread-like structures. Electron microscopy showed that the rod-like bodies were composed of abnormal fibrillar material. The parents showed minor abnormalities, which were interpreted as possible heterozygous effects. At the same time, Conen et al. (1963) reported a child with hypotonia and muscle weakness who had 'myogranules' on skeletal muscle biopsy. </p><p>The mother and daughter described by Ford (1961) as cases of 'congenital universal muscular hypoplasia of Krabbe' (159100) were shown by Hopkins et al. (1966) to have nemaline myopathy. Engel et al. (1964) reported a 16-year-old girl with nemaline myopathy and suggested that she had slow progression of the disease through late childhood. </p><p>Price et al. (1965) reported 3 cases. An 8.5-year-old white girl had generalized muscle weakness and hypotonia since birth. She walked with difficulty at age 17 months, and had difficulty arising from the floor. Her face was elongated, with decreased expression and a high-arched palate. She had proximal girdle muscle weakness and hypo- or areflexia. Two sibs were similarly affected. Two African American girls, aged 11 and 12 years, had diffuse muscle weakness from birth. Motor milestones were delayed. Both girls had elongated, dysmorphic, expressionless facies, jaw weakness, and very high-arched palate. One child was limited to a wheelchair, and the other walked only with great difficulty. </p><p>Pearson et al. (1967) described 3 affected sibs out of 8. The mother, although clinically normal, had minor histologic alterations of skeletal muscle. In 3 affected brothers born of unaffected parents, Danowski et al. (1973) found a distinct beta globulin peak upon serum protein electrophoresis. This sharp beta peak was caused by an increase in the C3 component of serum complement. </p><p>Jenis et al. (1969) described a white girl, born of unrelated parents, who showed extreme muscular weakness and hypotonia from birth and died of respiratory insufficiency at 2 months of age. Intranuclear and sarcoplasmic rod inclusions were found in muscle cells. </p><p>Meier et al. (1983, 1984) described nemaline myopathy as the cause of fatal cardiomyopathy in a 29-year-old woman. She had a leptosomal habitus but no neuromuscular abnormalities. Quadriceps biopsy showed type 1 fiber predominance and nemaline rods in about 50% of muscle fibers by trichrome staining and electron microscopy. Autopsy showed nemaline bodies in the myocardium, including the conducting tissue. The patient's mother and 1 of her sisters suffered sudden unexplained death at ages 47 and 37, respectively; sections of the sister's myocardium showed nemaline bodies. </p><p>Arts et al. (1978) suggested the existence of both dominant and recessive forms of nemaline or rod myopathy. The 2 forms could not be distinguished on clinical or histopathologic grounds. The authors found in 2 families that both parents of each index patient had rods and an increased number of fibers with central nuclei, a presumed heterozygous manifestation. </p><p>Kondo and Yuasa (1980) reviewed all reported cases of congenital nemaline myopathy and concluded that autosomal dominant inheritance was the only acceptable genetic hypothesis. </p><p>McMenamin et al. (1984) reported 2 infants with fatal nemaline myopathy. One presented at birth with severe hypotonia, respiratory failure, and contractures, and died shortly after the neonatal period. The other patient presented at age 2 months with hypotonia, and died of respiratory failure at age 7 months. Pathologic findings in both cases showed numerous rod bodies in the diaphragm and limb muscles. No abnormalities were seen in the central or peripheral nervous systems. </p><p>Schmalbruch et al. (1987) described the early fatal form of nemaline myopathy in 1 case and reviewed 13 reported cases. All died within the first year of life. Three affected sibs were reported by Neustein (1973) and 2 affected sibs were reported by Gillies et al. (1979). Harati et al. (1987) reported a case of nemaline myopathy presenting in adulthood as diaphragmatic paralysis. </p><p>Harati et al. (1987) reported a case of nemaline myopathy presenting in adulthood as diaphragmatic paralysis. </p><p>Wallgren-Pettersson (1989) reported follow-up of 12 patients with congenital nemaline myopathy. Ten showed clinical deterioration and 2 showed improvement. Muscle weakness was most severe in the facial muscles, flexors of the neck and trunk, dorsiflexors of the feet, and extensors of the toes. Distal limb muscles and limb-girdle muscles were more severely affected than proximal limb muscles. There were no signs of central nervous system involvement. Prognosis was influenced mainly by the presence of scoliosis and restricted respiratory capacity. </p><p>Maayan et al. (1986) described sleep hypoventilation in a brother and sister, aged 14.5 and 11.5 years, respectively, with nemaline myopathy. </p><p>Falga-Tirado et al. (1995) reported a case of adult-onset nemaline myopathy presenting as respiratory insufficiency without generalized muscle weakness. Serum muscle enzymes were normal, but biceps muscle biopsy showed abundant nemaline bodies. Diaphragmatic movement appeared to be normal by ultrasound of the chest and esophageal tonometry. The patient was successfully treated with nasal intermittent pressure ventilation. </p><p>Vendittelli et al. (1996) described a severe form of nemaline myopathy associated with early death in the neonate. Decreased fetal movement was noted during pregnancy in each case. One infant was born with joint contractures of the hands and feet, severe hypotonia, and edema of the hands and feet. Chest radiographs showed lung hypoplasia, thin ribs, and an elevated diaphragm. He died at the age of 6 days from respiratory failure. The second patient, a girl, was born from a pregnancy characterized by hydramnios hand persistent breech presentation. She showed respiratory failure, hypotonia, and inability to swallow, and died from respiratory failure at the age of 68 days. </p>
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<strong>Animal Model</strong>
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<p>In a review, Shelton and Engvall (2005) stated that models of nemaline rod myopathy had been described in Border Collie and Schipperke dogs and a family of cats. </p>
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<h4>
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<strong>REFERENCES</strong>
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<ol>
<li>
<p class="mim-text-font">
Anderson, S. L., Ekstein, J., Donnelly, M. C., Keefe, E. M., Toto, N. R., LeVoci, L. A., Rubin, B. Y.
<strong>Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene.</strong>
Hum. Genet. 115: 185-190, 2004.
[PubMed: 15221447]
[Full Text: https://doi.org/10.1007/s00439-004-1140-8]
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<li>
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Arts, W. F., Bethlem, J., Dingemans, K. P., Eriksson, A. W.
<strong>Investigations on the inheritance of nemaline myopathy.</strong>
Arch. Neurol. 35: 72-77, 1978.
[PubMed: 623532]
[Full Text: https://doi.org/10.1001/archneur.1978.00500260010002]
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</li>
<li>
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Conen, P. E., Murphy, E. G., Donohue, W. L.
<strong>Light and electron microscopic studies of &quot;myogranules&quot; in a child with hypotonia and muscle weakness.</strong>
Can. Med. Assoc. J. 89: 983-986, 1963.
[PubMed: 14076166]
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</li>
<li>
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Danowski, T. S., Fisher, E. R., Wald, N., Wester, J. W., Zawadzki, Z. A.
<strong>Rod myopathy: beta globulin peak and increased complement.</strong>
Metabolism 22: 597-604, 1973.
[PubMed: 4121348]
[Full Text: https://doi.org/10.1016/0026-0495(73)90073-5]
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</li>
<li>
<p class="mim-text-font">
Engel, W. K., Wanko, T., Fenichel, G. M.
<strong>Nemaline myopathy; a second case.</strong>
Arch. Neurol. 11: 22-39, 1964.
[PubMed: 14147679]
[Full Text: https://doi.org/10.1001/archneur.1964.00460190026003]
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<li>
<p class="mim-text-font">
Falga-Tirado, C., Perez-Peman, P., Ordi-Ros, J., Bofill, J. M., Balcells, E.
<strong>Adult onset of nemaline myopathy presenting as respiratory insufficiency.</strong>
Respiration 62: 353-354, 1995.
[PubMed: 8552868]
[Full Text: https://doi.org/10.1159/000196479]
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<li>
<p class="mim-text-font">
Ford, F. R.
<strong>Diseases of the Nervous System in Infancy, Childhood and Adolescence. (4th ed.).</strong>
Springfield, Ill.: Charles C Thomas (pub.) 1961. Pp. 1259-1260.
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<li>
<p class="mim-text-font">
Gibson, A.
<strong>Muscular infantilism.</strong>
Arch. Intern. Med. 27: 338-350, 1921.
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<li>
<p class="mim-text-font">
Gillies, C., Raye, J., Vasan, U., Hart, W. E., Goldblatt, P. J.
<strong>Nemaline rod myopathy: a possible cause of rapidly fatal infantile hypotonia.</strong>
Arch. Path. Lab. Med. 103: 1-5, 1979.
[PubMed: 581546]
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<li>
<p class="mim-text-font">
Harati, Y., Niakan, E., Bloom, K., Casar, G.
<strong>Adult onset of nemaline myopathy presenting as diaphragmatic paralysis.</strong>
J. Neurol. Neurosurg. Psychiat. 50: 108-110, 1987.
[PubMed: 3819745]
[Full Text: https://doi.org/10.1136/jnnp.50.1.108]
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<li>
<p class="mim-text-font">
Hopkins, I. J., Lindsey, J. R., Ford, F. R.
<strong>Nemaline myopathy. A long-term clinicopathologic study of affected mother and daughter.</strong>
Brain 89: 299-310, 1966.
[PubMed: 5939042]
[Full Text: https://doi.org/10.1093/brain/89.2.299]
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<li>
<p class="mim-text-font">
Jenis, E. H., Lindquist, R. R., Lister, R. C.
<strong>New congenital myopathy with crystalline intranuclear inclusions.</strong>
Arch. Neurol. 20: 281-287, 1969.
[PubMed: 5766493]
[Full Text: https://doi.org/10.1001/archneur.1969.00480090069011]
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<li>
<p class="mim-text-font">
Kondo, K., Yuasa, T.
<strong>Genetics of congenital nemaline myopathy.</strong>
Muscle Nerve 3: 308-315, 1980.
[PubMed: 6997732]
[Full Text: https://doi.org/10.1002/mus.880030407]
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<li>
<p class="mim-text-font">
Lehtokari, V.-L., Greenleaf, R. S., DeChene, E. T., Kellinsalmi, M., Pelin, K., Laing, N. G., Beggs, A. H., Wallgren-Pettersson, C.
<strong>The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.</strong>
Neuromusc. Disord. 19: 179-181, 2009.
[PubMed: 19232495]
[Full Text: https://doi.org/10.1016/j.nmd.2008.12.001]
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</li>
<li>
<p class="mim-text-font">
Lehtokari, V.-L., Kiiski, K., Sandaradura, S. A., Laporte, J., Repo, P., Frey, J. A., Donner, K., Marttila, M., Saunders, C., Barth, P. G., den Dunnen, J. T., Beggs, A. H., Clarke, N. F., North, K. N., Laing, N. G., Romero, N. B., Winder, T. L., Pelin, K., Wallgren-Pettersson, C.
<strong>Mutation update: the spectra of nebulin variants and associated myopathies.</strong>
Hum. Mutat. 35: 1418-1426, 2014.
[PubMed: 25205138]
[Full Text: https://doi.org/10.1002/humu.22693]
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<li>
<p class="mim-text-font">
Lehtokari, V.-L., Pelin, K., Sandbacka, M., Ranta, S., Donner, K., Muntoni, F., Sewry, C., Angelini, C., Bushby, K., Van den Bergh, P., Iannaccone, S., Laing, N. G., Wallgren-Pettersson, C.
<strong>Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.</strong>
Hum. Mutat. 27: 946-956, 2006.
[PubMed: 16917880]
[Full Text: https://doi.org/10.1002/humu.20370]
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</li>
<li>
<p class="mim-text-font">
Maayan, C., Springer, C., Armon, Y., Bar-Yishay, E., Shapira, Y., Godfrey, S.
<strong>Nemaline myopathy as a cause of sleep hypoventilation.</strong>
Pediatrics 77: 390-395, 1986.
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McMenamin, J. B., Curry, B., Taylor, G. P., Becker, L. E., Murphy, E. G.
<strong>Fatal nemaline myopathy in infancy.</strong>
Can. J. Neurol. Sci. 11: 305-309, 1984.
[PubMed: 6733612]
[Full Text: https://doi.org/10.1017/s0317167100045583]
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Meier, C., Gertsch, M., Zimmerman, A., Voellmy, W., Geissbuhler, J.
<strong>Nemaline myopathy presenting as cardiomyopathy. (Letter)</strong>
New Eng. J. Med. 308: 1536-1537, 1983.
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[Full Text: https://doi.org/10.1056/nejm198306233082515]
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Meier, C., Voellmy, W., Gertsch, M., Zimmermann, A., Geissbuhler, J.
<strong>Nemaline myopathy appearing in adults as cardiomyopathy: a clinicopathologic study.</strong>
Arch. Neurol. 41: 443-445, 1984.
[PubMed: 6703949]
[Full Text: https://doi.org/10.1001/archneur.1984.04050160109025]
</p>
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Neustein, H. B.
<strong>Nemaline myopathy: a family study with three autopsied cases.</strong>
Arch. Path. 96: 192-195, 1973.
[PubMed: 4124693]
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Ottenheijm, C. A. C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H.
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[Full Text: https://doi.org/10.1093/hmg/ddp168]
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Pearson, C. M., Coleman, R. F., Fowler, W. M., Mommaerts, W. F., Munsat, T. L., Peter, J. B.
<strong>Skeletal muscle. Basic and clinical aspects and illustrative new diseases.</strong>
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Pelin, K., Hilpela, P., Donner, K., Sewry, C., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M.-L., Centner, T., Hanefeld, F., Odent, S., Fardeau, M., Urtizberea, J. A., Muntoni, F., Dubowitz, V., Beggs, A. H., Laing, N. G., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
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[Full Text: https://doi.org/10.1073/pnas.96.5.2305]
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Pelin, K., Ridanpaa, M., Donner, K., Wilton, S., Krishnarajah, J., Laing, N., Kolmerer, B., Millevoi, S., Labeit, S., de la Chapelle, A., Wallgren-Pettersson, C.
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Europ. J. Hum. Genet. 5: 229-234, 1997.
[PubMed: 9359044]
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Price, H. M., Gordon, G. B., Pearson, C. M., Munsat, T. L., Blumberg, J. M.
<strong>New evidence for excessive accumulation of Z-band material in nemaline myopathy.</strong>
Proc. Nat. Acad. Sci. 54: 1398-1406, 1965.
[PubMed: 5218258]
[Full Text: https://doi.org/10.1073/pnas.54.5.1398]
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Romero, N. B., Lehtokari, V.-L., Quijano-Roy, S., Monnier, N., Claeys, K. G., Carlier, R. Y., Pellegrini, N., Orlikowski, D., Barois, A., Laing, N. G., Lunardi, J., Fardeau, N., Pelin, K., Wallgren-Pettersson, C.
<strong>Core-rod myopathy caused by mutations in the nebulin gene.</strong>
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181bacf45]
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Sanoudou, D., Beggs, A. H.
<strong>Clinical and genetic heterogeneity in nemaline myopathy--a disease of skeletal muscle thin filaments.</strong>
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Schmalbruch, H., Kamieniecka, Z., Arroe, M.
<strong>Early fatal nemaline myopathy: case report and review.</strong>
Dev. Med. Child Neurol. 29: 800-804, 1987.
[PubMed: 2826279]
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Shy, G. M., Engel, W. K., Somers, J. E., Wanko, T.
<strong>Nemaline Myopathy: a new congenital myopathy.</strong>
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[PubMed: 14090530]
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Vendittelli, F., Manciet-Labarchede, C., Gilbert-Dussardier, B.
<strong>Nemaline myopathy in the neonate: two case reports.</strong>
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[PubMed: 8580725]
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Wallgren-Pettersson, C., Donner, K., Sewry, C., Bijlsma, E., Lammens, M., Bushby, K., Giovannucci Uzielli, M. L., Lapi, E., Odent, S., Akcoren, Z., Topaloglu, H., Pelin, K.
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Wallgren-Pettersson, C.
<strong>Congenital nemaline myopathy: a clinical follow-up study of twelve patients.</strong>
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[PubMed: 2926439]
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Cassandra L. Kniffin - updated : 05/21/2021<br>Cassandra L. Kniffin - updated : 03/27/2018<br>Cassandra L. Kniffin - updated : 4/18/2011<br>George E. Tiller - updated : 3/30/2010<br>Cassandra L. Kniffin - updated : 10/16/2009<br>Cassandra L. Kniffin - updated : 9/19/2006<br>Marla J. F. O&#x27;Neill - updated : 4/18/2005<br>Cassandra L. Kniffin - updated : 4/4/2005<br>Victor A. McKusick - updated : 4/28/1999<br>Victor A. McKusick - updated : 10/30/1997<br>Orest Hurko - updated : 8/15/1995
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