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<label for="email-from" class="action-panel-label">
From:
</label>
<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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx">
<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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx">
<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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx">
<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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx">
<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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx">
<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="39643435">
<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://jmg.bmj.com/lookup/pmidlookup?view=long&amp;pmid=39643435"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3051&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=39643435&amp;db=pubmed&amp;nlmid=2985087R"
title="See full text options at HighWire"
data-ga-category="full_text"
data-ga-action="HighWire"
data-ga-label="39643435"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-bmjjournals_final.gif" alt="HighWire full text link"><span class="text">
HighWire
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/39643435/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=39643435&amp;db=pubmed&amp;nlmid=2985087R"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="39643435"
><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="/39643435/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/39643435/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="39643435" 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%2F39643435%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="2RsfnNodWMwdkramZBvwGOXaFhqhAYZdjEck0DRzwnjHeSgcCU8yaWtOdl8ttzxx"><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"
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2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bivona+S&amp;cauthor_id=39643435"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Stephanie Bivona">Stephanie Bivona</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA." 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"
href="/?term=Peart+L&amp;cauthor_id=39643435"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="LéShon Peart">LéShon Peart</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA." 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"
href="/?term=Gultekin+SH&amp;cauthor_id=39643435"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Sakir Humayun Gultekin">Sakir Humayun Gultekin</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a></sup><span class="semicolon">;&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Undiagnosed+Diseases+Network%5BCorporate+Author%5D"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Undiagnosed Diseases Network">Undiagnosed Diseases Network</a><span class="semicolon">;&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bademci+G&amp;cauthor_id=39643435"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Guney Bademci">Guney Bademci</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA." 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"
href="/?term=Tekin+M&amp;cauthor_id=39643435"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Mustafa Tekin">Mustafa Tekin</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA mtekin@med.miami.edu." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="semicolon">;&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Undiagnosed+Diseases+Network+NIH%5BCorporate+Author%5D"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Undiagnosed Diseases Network NIH">Undiagnosed Diseases Network NIH</a></span>
</div>
</div>
<div class="collaborations">
<h3 class="title">
Collaborators
</h3>
<ul class="group-list">
<li>
<div class="authors-list">
<span class="authors-list-item "><a class="full-name"
href="/?term=Acosta+MT"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Maria T Acosta">Maria T Acosta</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Adams+DR"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="David R Adams">David R Adams</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Afzali+B"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Ben Afzali">Ben Afzali</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Al-Beshri+A"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Ali Al-Beshri">Ali Al-Beshri</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Allworth+A"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Aimee Allworth">Aimee Allworth</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Alvarez+RL"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Raquel L Alvarez">Raquel L Alvarez</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Alvey+J"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Justin Alvey">Justin Alvey</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Andrews+A"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Ashley Andrews">Ashley Andrews</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Ashley+EA"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Euan A Ashley">Euan A Ashley</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bacino+CA"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Carlos A Bacino">Carlos A Bacino</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bademci+G"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Guney Bademci">Guney Bademci</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Balasubramanyam+A"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Ashok Balasubramanyam">Ashok Balasubramanyam</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Baldridge+D"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Dustin Baldridge">Dustin Baldridge</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bale+J"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Jim Bale">Jim Bale</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bamshad+M"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Michael Bamshad">Michael Bamshad</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Barbouth+D"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Deborah Barbouth">Deborah Barbouth</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bayrak-Toydemir+P"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Pinar Bayrak-Toydemir">Pinar Bayrak-Toydemir</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Beck+A"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Anita Beck">Anita Beck</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Beggs+AH"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Alan H Beggs">Alan H Beggs</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Behrens+E"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Edward Behrens">Edward Behrens</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bejerano+G"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Gill Bejerano">Gill Bejerano</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bellen+HJ"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Hugo J Bellen">Hugo J Bellen</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bennett+J"
ref="linksrc=author_name_link"
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data-ga-label="Jimmy Bennett">Jimmy Bennett</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bernstein+JA"
ref="linksrc=author_name_link"
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data-ga-label="Jonathan A Bernstein">Jonathan A Bernstein</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Berry+GT"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Gerard T Berry">Gerard T Berry</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bican+A"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Anna Bican">Anna Bican</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bivona+S"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Stephanie Bivona">Stephanie Bivona</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Blue+E"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Elizabeth Blue">Elizabeth Blue</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bohnsack+J"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="John Bohnsack">John Bohnsack</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Bonner+D"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Devon Bonner">Devon Bonner</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Borja+N"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Nicholas Borja">Nicholas Borja</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Botto+L"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Lorenzo Botto">Lorenzo Botto</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Briere+LC"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Lauren C Briere">Lauren C Briere</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Burke+EA"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Elizabeth A Burke">Elizabeth A Burke</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Burrage+LC"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Lindsay C Burrage">Lindsay C Burrage</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Butte+MJ"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Manish J Butte">Manish J Butte</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Byers+P"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Peter Byers">Peter Byers</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Byrd+WE"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="William E Byrd">William E Byrd</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Callaway+K"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Kaitlin Callaway">Kaitlin Callaway</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Carey+J"
ref="linksrc=author_name_link"
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data-ga-label="John Carey">John Carey</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Carvalho+G"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="George Carvalho">George Carvalho</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Cassini+T"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Thomas Cassini">Thomas Cassini</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Chanprasert+S"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Sirisak Chanprasert">Sirisak Chanprasert</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Chao+HT"
ref="linksrc=author_name_link"
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data-ga-label="Hsiao-Tuan Chao">Hsiao-Tuan Chao</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Chinn+I"
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data-ga-label="Ivan Chinn">Ivan Chinn</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Clark+GD"
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data-ga-label="Gary D Clark">Gary D Clark</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Coakley+TR"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Terra R Coakley">Terra R Coakley</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Cobban+LA"
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data-ga-label="Laurel A Cobban">Laurel A Cobban</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Cogan+JD"
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data-ga-label="Joy D Cogan">Joy D Cogan</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Coggins+M"
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data-ga-label="Matthew Coggins">Matthew Coggins</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Sessions+Cole+F"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="F Sessions Cole">F Sessions Cole</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Corner+B"
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data-ga-label="Brian Corner">Brian Corner</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Corona+RI"
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data-ga-label="Rosario I Corona">Rosario I Corona</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Craigen+WJ"
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data-ga-label="William J Craigen">William J Craigen</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Crouse+AB"
ref="linksrc=author_name_link"
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data-ga-label="Andrew B Crouse">Andrew B Crouse</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Cuddapah+V"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Vishnu Cuddapah">Vishnu Cuddapah</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Cunningham+M"
ref="linksrc=author_name_link"
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data-ga-label="Michael Cunningham">Michael Cunningham</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=D%27Souza+P"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Precilla D&#x27;Souza">Precilla D&#x27;Souza</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Dai+H"
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data-ga-label="Hongzheng Dai">Hongzheng Dai</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Darr+K"
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data-ga-label="Kahlen Darr">Kahlen Darr</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Dasari+S"
ref="linksrc=author_name_link"
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data-ga-label="Surendra Dasari">Surendra Dasari</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Davis+J"
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data-ga-label="Joie Davis">Joie Davis</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Delgado+M"
ref="linksrc=author_name_link"
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data-ga-label="Margaret Delgado">Margaret Delgado</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Dell%27Angelica+EC"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Esteban C Dell&#x27;Angelica">Esteban C Dell&#x27;Angelica</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Dipple+K"
ref="linksrc=author_name_link"
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data-ga-label="Katrina Dipple">Katrina Dipple</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Doherty+D"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Daniel Doherty">Daniel Doherty</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Dorrani+N"
ref="linksrc=author_name_link"
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data-ga-action="author_link"
data-ga-label="Naghmeh Dorrani">Naghmeh Dorrani</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Douglas+J"
ref="linksrc=author_name_link"
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data-ga-label="Jessica Douglas">Jessica Douglas</a><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Douine+ED"
ref="linksrc=author_name_link"
data-ga-category="search"
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><sup class="key">1</sup> Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.</li>
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><sup class="key">2</sup> John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.</li>
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><sup class="key">4</sup> Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA mtekin@med.miami.edu.</li>
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<p>
<i>KIF21A</i> encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant in <i>KIF21A</i> p.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts. She presented with progressive peripheral neuropathy, hypoplasia of the corpus callosum and strabismus in the absence of CFEOM. Protein modelling predicts that the KIF21A variant leads to significant alterations in its structure as well as binding with TUBB3. Co-immunoprecipitation data was consistent with decreased binding of KIF21A p.Leu664Pro to TUBB3 in vitro compared with reference. Taken together, we delineate a <i>KIF21A</i>-related phenotype defined by progressive peripheral neuropathy, brain anomalies, developmental delay and comitant strabismus potentially stemming from the disruption of the interaction between KIF21A and TUBB3.
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Keywords:
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Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Eye Diseases; Human Genetics; Nervous System Diseases.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Competing interests: None declared.</p>
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<div class="figure-caption-contents"><b> A. </b> Illustration of KIF21A with…</div>
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<div class="figure-caption-contents"><b> A. </b> Illustration of KIF21A with leucine at amino acid 664 (Leu664) compared to…</div>
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FIGURE 1.
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<div class="figure-caption-contents"><b>A.</b> Illustration of KIF21A with leucine at amino acid 664 (Leu664) compared to proline at amino acid 664 (Pro664) with predicted salt bridges formed between Leu664 and Leu660, Ile661, Leu756, with a comparison of Pro664 demonstrating a reduction in ionic interactions amongst these residues. <b>B.</b> Predictive modeling of this effect on TUBB3 interaction through comparison of predicted salt bridges formed between KIF21A and TUBB3 originating at KIF21A residues Glu1089, Arg1423, Lys881, and Lys847 (left), with the Pro664 disrupting most of these and producing ionic interactions with TUBB3 at KIF21A residues Lys847, Arg850, Arg851, Lys903, Lys901 and Lys1220 (right). TUBB3 residues depicted in magenta, KIF21A residues in purple. <b>C.</b> Co-immunoprecipitation assay with western blot image demonstrating the presence of TUBB3 protein co-eluted alongside KIF21A protein at 55 kD (*). c-Myc refers to the pure c-Myc peptide used as a kit efficiency control; Con denotes HEK293 cells only; Ref is the reference KIF21A; Var is the KIF21A p.Pro644. <b>D.</b> Relative abundance of eluted TUBB3 compared between KIF21A reference and KIF21A p.Leu664Pro, with bars representing standard error of the mean, ** representing p ≤ 0.01, no. transfections = 3.</div>
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<div id="supplementary-concepts" class="supplementary-concepts keywords-section">
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Supplementary concepts
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