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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21665002">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(11)00203-5"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21665002&amp;db=pubmed&amp;nlmid=0370475"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="21665002"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21665002/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21665002&amp;db=pubmed&amp;nlmid=0370475"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21665002"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21665002/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21665002/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21665002" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21665002%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="luyyZ7Mq3LOBm8GJKcSLXXSy2wB11jHKChiDCXfMDmB5gzMznvvNr5ocAAjdUUf4"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
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<h1 class="heading-title">
A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis
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><sup class="key">6</sup> Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; MRC Centre for Neuromuscular Disorders, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.</li>
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><sup class="key">7</sup> Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; RJAH Orthopaedic Hospital, Oswestry, SY107AG, UK.</li>
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><sup class="key">8</sup> Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, 1130033, Japan.</li>
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><sup class="key">9</sup> The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.</li>
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><sup class="key">10</sup> Department of Pediatrics, Child Neurology Unit, Hacettepe Children&#x27;s Hospital, 06100, Ankara, Turkey.</li>
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><sup class="key">11</sup> National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan. Electronic address: nishino@ncnp.go.jp.</li>
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A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis
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<span class="authors-list-item "><span class="full-name">Satomi Mitsuhashi</span><span class="citation-separator">&nbsp;et al.</span></span>
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<span class="authors-list-item "><a class="full-name"
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data-ga-label="Satomi Mitsuhashi">Satomi Mitsuhashi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan." href="#short-view-affiliation-1" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Aya Ohkuma">Aya Ohkuma</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Beril Talim">Beril Talim</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pathology Unit, Hacettepe Children&#x27;s Hospital, Ankara, 06100, Turkey." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Minako Karahashi">Minako Karahashi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="School of Pharmaceutical Sciences, Kitasato University, Tokyo, 1088641, Japan." href="#short-view-affiliation-3" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Tomoko Koumura">Tomoko Koumura</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="School of Pharmaceutical Sciences, Kitasato University, Tokyo, 1088641, Japan." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Chieko Aoyama">Chieko Aoyama</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Biochemistry, Dokkyo Medical University School of Medicine, Mibu, 3210293, Japan." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Mana Kurihara">Mana Kurihara</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, The Kanagawa Rehabilitation Center, Kanagawa, 2430121, Japan." href="#short-view-affiliation-5" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ros Quinlivan">Ros Quinlivan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; MRC Centre for Neuromuscular Disorders, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK." href="#short-view-affiliation-6" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Caroline Sewry">Caroline Sewry</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; RJAH Orthopaedic Hospital, Oswestry, SY107AG, UK." href="#short-view-affiliation-7" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Hiroaki Mitsuhashi">Hiroaki Mitsuhashi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Burcu Koksal">Burcu Koksal</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pathology Unit, Hacettepe Children&#x27;s Hospital, Ankara, 06100, Turkey." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Gulsev Kale">Gulsev Kale</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pathology Unit, Hacettepe Children&#x27;s Hospital, Ankara, 06100, Turkey." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Kazutaka Ikeda">Kazutaka Ikeda</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, 1130033, Japan." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ryo Taguchi">Ryo Taguchi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, 1130033, Japan." href="#short-view-affiliation-8" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Satoru Noguchi">Satoru Noguchi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Roger B Sher">Roger B Sher</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Jackson Laboratory, Bar Harbor, Maine, 04609, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Gregory A Cox">Gregory A Cox</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Jackson Laboratory, Bar Harbor, Maine, 04609, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Haluk Topaloglu">Haluk Topaloglu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Child Neurology Unit, Hacettepe Children&#x27;s Hospital, 06100, Ankara, Turkey." href="#short-view-affiliation-10" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Ichizo Nishino">Ichizo Nishino</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan. Electronic address: nishino@ncnp.go.jp." href="#short-view-affiliation-11" ref="linksrc=author_aff">
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><sup class="key">1</sup> National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan.</li>
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><sup class="key">2</sup> Department of Pediatrics, Pathology Unit, Hacettepe Children&#x27;s Hospital, Ankara, 06100, Turkey.</li>
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><sup class="key">3</sup> School of Pharmaceutical Sciences, Kitasato University, Tokyo, 1088641, Japan.</li>
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><sup class="key">4</sup> Department of Biochemistry, Dokkyo Medical University School of Medicine, Mibu, 3210293, Japan.</li>
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><sup class="key">5</sup> Department of Pediatrics, The Kanagawa Rehabilitation Center, Kanagawa, 2430121, Japan.</li>
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><sup class="key">6</sup> Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; MRC Centre for Neuromuscular Disorders, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.</li>
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><sup class="key">7</sup> Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK; RJAH Orthopaedic Hospital, Oswestry, SY107AG, UK.</li>
<li data-affiliation-id="short-view-affiliation-8"
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><sup class="key">8</sup> Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, 1130033, Japan.</li>
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><sup class="key">9</sup> The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.</li>
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><sup class="key">10</sup> Department of Pediatrics, Child Neurology Unit, Hacettepe Children&#x27;s Hospital, 06100, Ankara, Turkey.</li>
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><sup class="key">11</sup> National Institute of Neuroscience, Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Tokyo 1878502, Japan. Electronic address: nishino@ncnp.go.jp.</li>
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Congenital muscular dystrophy is a heterogeneous group of inherited muscle diseases characterized clinically by muscle weakness and hypotonia in early infancy. A number of genes harboring causative mutations have been identified, but several cases of congenital muscular dystrophy remain molecularly unresolved. We examined 15 individuals with a congenital muscular dystrophy characterized by early-onset muscle wasting, mental retardation, and peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center on muscle biopsy, and we have identified homozygous or compound heterozygous mutations in the gene encoding choline kinase beta (CHKB). This is the first enzymatic step in a biosynthetic pathway for phosphatidylcholine, the most abundant phospholipid in eukaryotes. In muscle of three affected individuals with nonsense mutations, choline kinase activities were undetectable, and phosphatidylcholine levels were decreased. We identified the human disease caused by disruption of a phospholipid de novo biosynthetic pathway, demonstrating the pivotal role of phosphatidylcholine in muscle and brain.
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<div class="figure-caption-contents"><p> Muscle Pathology of the Affected… </p></div>
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<div class="figure-caption-contents"><p> Muscle Pathology of the Affected Individuals Cross-sections of muscle fiber from a human… </p></div>
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<div class="figure-caption-contents">Muscle Pathology of the Affected Individuals Cross-sections of muscle fiber from a human control and individual 4. (A) On H&E staining, nonspecific dystrophic features with necrotic and regenerating fibers, internalized nuclei, and endomysial fibrosis are seen. The scale bar represents 25 μm. (B) On cytochrome c oxidase staining, enlarged mitochondria at the periphery and central areas devoid of mitochondria were seen. The scale bar represents 20 μm. (C) On NADH-TR staining, the intermyofibrillar network was preserved even in the central areas that are devoid of mitochondria, suggesting the presence of myofibrils and only absence of mitochondria. The scale bar represents 20 μm. (D) Electron microscopy confirmed enlarged mitochondria. The scale bar represents 1 μm.</div>
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<div class="figure-caption-contents">Choline Kinase Activity and Phospholipid Analyses (A) In muscle tissue from individuals 2, 3, and 4, CHK activity cannot be detected (n = 3). Data represent the mean of three individuals. (B) PC and PE content in frozen biopsied muscle tissues from individuals 2, 3, and 4 and hindlimb muscles from 8-week-old <i>rmd</i> mice (n = 4) and control littermates (n = 5) were analyzed by thin-layer chromatography followed by phosphorus analysis. PC and the PC/PE ratio are significantly decreased in affected individuals and <i>rmd</i> mice (n = 3 for humans, n = 4 for <i>rmd</i> mice, n = 5 for littermates). (C) Fatty acid composition of PC molecular species in muscles and isolated mitochondria from hindlimb muscles of <i>rmd</i> mice are determined by electrospray ionization mass spectrometry (ESI-MS). We observed that 34:1-PC (16:0-18:1), 36:4-PC (16:0-20:4), and 38:6-PC (16:0-22:6) species are significantly decreased, whereas 36:2-PC (18:0-18:2) is increased in <i>rmd</i> muscle. Similarly, in isolated mitochondria from hindlimb muscle, 36:4-PC (16:0-20:4) and 38:6-PC (16:0-22:6) species are decreased, whereas 36:2-PC (18:0-18:2) is increased. In muscle and isolated mitochondria, the 38:6-PC molecular species is profoundly decreased (n = 6 for muscle, n = 5 for isolated mitochondria). Mitochondria from skeletal muscles of whole hindlimbs of <i>rmd</i> mice were isolated by the differential centrifugation method. Fresh muscle was minced and homogenized with a motor-driven Teflon pestle homogenizer with ice-cold mitochondrial isolation buffer (10 mM Tris-HCl [pH 7.2], 320 mM sucrose, 1mM EDTA, 1mM DTT, 1 mM PMSF, 1 mg/ml BSA, and protease inhibitor cocktail [Roche]) and centrifuged at 1,500 × <i>g</i> for 5 min. The supernatant fraction was centrifuged at 15,000 × <i>g</i> for 20 min, the pellet was resuspended in mitochondrial isolation buffer, and the centrifugation/resuspension was repeated twice more. All data are presented as means ± standard deviation (SD). Means were compared by analysis with a two-tailed t test via R software version 2.11.0.</div>
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