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|
||
<div class="search-links-wrapper content-page-layout">
|
||
<div class="search-links">
|
||
<a href="/advanced/"
|
||
class="search-input-link adv-search-link"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="adv_search">Advanced</a>
|
||
|
||
|
||
<a href="/clipboard/"
|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26642243%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26642243%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</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="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 26642243 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 26642243"/>
|
||
<input type="hidden" name="email-subject-hash" value="20675a6341d300f5e9eacb1c9b785c92036643e633b7632b82180b54cf628854"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" 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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
|
||
|
||
<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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
|
||
|
||
<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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1">
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</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="26642243">
|
||
<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://doi.org/10.1038/ng.3459"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3094&itool=Abstract-def&log$=linkouticon&uid=26642243&db=pubmed&nlmid=9216904"
|
||
title="See full text options at Nature Publishing Group"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Nature Publishing Group"
|
||
data-ga-label="26642243"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="Nature Publishing Group full text link"><span class="text">
|
||
|
||
Nature Publishing Group
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/26642243/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=26642243&db=pubmed&nlmid=9216904"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="26642243"
|
||
><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="/26642243/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/26642243/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="26642243" 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%2F26642243%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="34WLi0dePoGD8FFEikzeR0XPFxTg6UhHkRGQVQGApZt726LuVDcgl8ttdBBsZvP1"><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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
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-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
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="collections_button"
|
||
data-ga-action="click"
|
||
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="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
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Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease
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6
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3
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3
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8
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9
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7
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4
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10
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11
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12
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1
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1
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1
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1
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1
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13
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14
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15
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16
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7
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4
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3
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16
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6
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1
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18
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1
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1
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<li data-affiliation-id="full-view-affiliation-4"
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<li data-affiliation-id="full-view-affiliation-5"
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<li data-affiliation-id="full-view-affiliation-8"
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Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease
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data-ga-label="Claudia Ouyang">Claudia Ouyang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chen+C&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
|
||
data-ga-label="Celeste Chen">Celeste Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chin+DT&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
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||
data-ga-label="David T Chin">David T Chin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Zaal+K&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
|
||
data-ga-label="Kristien Zaal">Kristien Zaal</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Light Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chandrasekharappa+SC&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
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||
data-ga-label="Settara C Chandrasekharappa">Settara C Chandrasekharappa</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
|
||
9
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hanson+EP&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
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||
data-ga-label="Eric P Hanson">Eric P Hanson</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Yu+Z&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Zhen Yu">Zhen Yu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Laboratory of Cardiovascular Regenerative Medicine, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff">
|
||
4
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Mullikin+JC&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
|
||
data-ga-label="James C Mullikin">James C Mullikin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="National Institute of Health Intramural Sequencing Center, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
|
||
10
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hasni+SA&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Sarfaraz A Hasni">Sarfaraz A Hasni</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systemic Autoimmune Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-11" ref="linksrc=author_aff">
|
||
11
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Wertz+IE&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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data-ga-action="author_link"
|
||
data-ga-label="Ingrid E Wertz">Ingrid E Wertz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Molecular Oncology, Genentech, Inc., San Francisco, California, USA." href="#short-view-affiliation-12" ref="linksrc=author_aff">
|
||
12
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ombrello+AK&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Amanda K Ombrello">Amanda K Ombrello</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Stone+DL&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Deborah L Stone">Deborah L Stone</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hoffmann+P&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Patrycja Hoffmann">Patrycja Hoffmann</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Jones+A&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Anne Jones">Anne Jones</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Barham+BK&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Beverly K Barham">Beverly K Barham</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Leavis+HL&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Helen L Leavis">Helen L Leavis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands." href="#short-view-affiliation-13" ref="linksrc=author_aff">
|
||
13
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=van+Royen-Kerkof+A&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Annet van Royen-Kerkof">Annet van Royen-Kerkof</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, the Netherlands." href="#short-view-affiliation-14" ref="linksrc=author_aff">
|
||
14
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Sibley+C&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Cailin Sibley">Cailin Sibley</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, Oregon, USA." href="#short-view-affiliation-15" ref="linksrc=author_aff">
|
||
15
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Batu+ED&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ezgi D Batu">Ezgi D Batu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey." href="#short-view-affiliation-16" ref="linksrc=author_aff">
|
||
16
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=G%C3%BCl+A&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ahmet Gül">Ahmet Gül</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Internal Medicine, Istanbul University, Istanbul, Turkey." href="#short-view-affiliation-17" ref="linksrc=author_aff">
|
||
17
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Siegel+RM&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Richard M Siegel">Richard M Siegel</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Boehm+M&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Manfred Boehm">Manfred Boehm</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Laboratory of Cardiovascular Regenerative Medicine, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff">
|
||
4
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Milner+JD&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Joshua D Milner">Joshua D Milner</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Genetics and Pathogenesis of Allergy Section, National Institute of Allergy and Infectious Diseases, Laboratory of Allergic Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ozen+S&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Seza Ozen">Seza Ozen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey." href="#short-view-affiliation-16" ref="linksrc=author_aff">
|
||
16
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Gadina+M&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Massimo Gadina">Massimo Gadina</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA." href="#short-view-affiliation-6" ref="linksrc=author_aff">
|
||
6
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chae+J&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="JaeJin Chae">JaeJin Chae</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Laxer+RM&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ronald M Laxer">Ronald M Laxer</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada." href="#short-view-affiliation-18" ref="linksrc=author_aff">
|
||
18
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Kastner+DL&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Daniel L Kastner">Daniel L Kastner</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Aksentijevich+I&cauthor_id=26642243"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ivona Aksentijevich">Ivona Aksentijevich</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup></span>
|
||
</div>
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="affiliations">
|
||
<h3 class="title">
|
||
Affiliations
|
||
</h3>
|
||
<ul class="item-list">
|
||
|
||
<li data-affiliation-id="short-view-affiliation-1"
|
||
id="short-view-affiliation-1"
|
||
><sup class="key">1</sup> Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-2"
|
||
id="short-view-affiliation-2"
|
||
><sup class="key">2</sup> Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-3"
|
||
id="short-view-affiliation-3"
|
||
><sup class="key">3</sup> Genetics and Pathogenesis of Allergy Section, National Institute of Allergy and Infectious Diseases, Laboratory of Allergic Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-4"
|
||
id="short-view-affiliation-4"
|
||
><sup class="key">4</sup> Laboratory of Cardiovascular Regenerative Medicine, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-5"
|
||
id="short-view-affiliation-5"
|
||
><sup class="key">5</sup> FMF Arthritis Vasculitis and Orphan Disease Research Center (FAVOR), Gulhane Military Medical Academy, Ankara, Turkey.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-6"
|
||
id="short-view-affiliation-6"
|
||
><sup class="key">6</sup> Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-7"
|
||
id="short-view-affiliation-7"
|
||
><sup class="key">7</sup> Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-8"
|
||
id="short-view-affiliation-8"
|
||
><sup class="key">8</sup> Light Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-9"
|
||
id="short-view-affiliation-9"
|
||
><sup class="key">9</sup> Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-10"
|
||
id="short-view-affiliation-10"
|
||
><sup class="key">10</sup> National Institute of Health Intramural Sequencing Center, National Human Genome Research Institute, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-11"
|
||
id="short-view-affiliation-11"
|
||
><sup class="key">11</sup> Systemic Autoimmune Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-12"
|
||
id="short-view-affiliation-12"
|
||
><sup class="key">12</sup> Department of Molecular Oncology, Genentech, Inc., San Francisco, California, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-13"
|
||
id="short-view-affiliation-13"
|
||
><sup class="key">13</sup> Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-14"
|
||
id="short-view-affiliation-14"
|
||
><sup class="key">14</sup> Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.</li>
|
||
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<li data-affiliation-id="short-view-affiliation-15"
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><sup class="key">15</sup> Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, Oregon, USA.</li>
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<li data-affiliation-id="short-view-affiliation-16"
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><sup class="key">16</sup> Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.</li>
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<li data-affiliation-id="short-view-affiliation-17"
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><sup class="key">17</sup> Department of Internal Medicine, Istanbul University, Istanbul, Turkey.</li>
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<li data-affiliation-id="short-view-affiliation-18"
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><sup class="key">18</sup> Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.</li>
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Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB-mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.
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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"><bold>Competing financial interests</bold></p>
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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">The authors declare no competing financial interests</p>
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<p> Figure 1. TNFAIP3 mutations cause a dominantly… </p>
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<p> Figure 1. TNFAIP3 mutations cause a dominantly inherited systemic inflammatory disease </p>
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<div class="figure-caption-contents"><p> ( <b> a </b> ) Pedigrees… </p></div>
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Figure 1. TNFAIP3 mutations cause a dominantly inherited systemic inflammatory disease
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<div class="figure-caption-contents">(<b>a</b>) Pedigrees of 5 families with heterozygous mutations in the <i>TNFAIP3</i> gene. WT indicates wild-type <i>TNFAIP3</i> alleles; M1, M2, M3, M4 and M5 indicate mutant alleles. The individuals selected for exome sequencing are marked with asterisk. NA: an affected sister of P6 had similar symptoms but was not available for this study. (<b>b</b>) Clinical manifestations in patients: chorioretinal scarring and macular fibrosis secondary to retinal vasculitis causing a significant visual impairment (upper panel), recurrent oral ulcers (middle panel), axillary dermal abscesses and a pathergy-positive response (bottom panel). (<b>c</b>) Schematic of TNFAIP3/A20 protein domains. Deubiquitinating (DUB) activity of A20 is mediated by the ovarian tumor (OTU) domain. ZFs mediate A20 ubiquitin ligase activity and binding to K63-linked ubiquitin chains. The locations of the mutations are indicated with red arrows. These mutations are predicted to affect A20 protein interactions, dimerization and its enzymatic activities. (<b>d-e</b>) Reduced of TNFAIP3/A20 expression in patients’ PBMCs and fibroblasts. (d) Whole cell lysates were prepared from PBMCs isolated from three patients from Family 1, a healthy donor (C1), and purified control lymphocytes (Lym). Immunoblotting was performed against the N-terminus of A20. (e) Whole cell lysates from a healthy donor (C2) and patient P6 cultured fibroblast cells were either blotted with A20 N-terminal specific antibody (lane 3 and 4) or immunoprecipitated with one A20 N-terminal antibody and subsequently blotted with another A20 N-terminal antibody (lane 5 and 6). 293T lysates transfected with either FLAG-tagged wild-type (WT) A20 (lane 1) or A20 mutant L227* (lane 2) served as controls.</div>
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<p> Figure 2. Enhanced NFκB signaling in transiently… </p>
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<p> Figure 2. Enhanced NFκB signaling in transiently transfected HEK293T cells and patients’ cells </p>
|
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Figure 2. Enhanced NFκB signaling in transiently transfected HEK293T cells and patients’ cells
|
||
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|
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|
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|
||
<div class="figure-caption-contents">(<b>a</b>) The TNFAIP3/A20 mutants do not antagonize the inhibitory effects of wild type TNFAIP3/A20 on TNF-induced NFκB activation. HEK293T cells were transiently transfected with a NFκB reporter plasmid, Renilla luciferase control vector, and expression plasmids for either GFP-tagged wild-type or mutant A20. Plasmid expressing IκBα served as a positive control. Results are plotted as luc/ren to compensate for differences in transfection efficiency. One representative result of three independent experiments is shown. Values are expressed as mean of duplicates ± S.E.M. Protein expression of the transfected plasmids was confirmed by western blotting of cell lysates. (<b>b</b>) Stimulated cells from A20-deficient patients show increased IκBα degradation and increased IKKα/β and MAPK activities. PBMCs from patient P6 were stimulated with TNF for the time period indicated in the graph. Whole cell lysates were immunoblotted against respective target proteins. Healthy individuals and an unrelated patient with SLE served as controls. (<b>c</b>) Fibroblasts derived from A20-deficient patients show increased levels of phospho-IκBα, phospho-IKKα/β and MAPK activity. Whole cell lysates from TNF-stimulated fibroblasts were immunoblotted against respective target proteins. (<b>d</b>) Cytosolic and nuclear fractions were prepared from patient P9 and immunoblotted with antibodies against p65, A20, and β-actin, respectively. (<b>e</b>) Quantified nuclear NFκB p65 immunofluorescence staining in patients’ and controls’ fibroblasts under no-stimulation (left panel) and stimulation (right panel). Patient fibroblasts are significantly more activated than control fibroblasts (P<0.0001, Mann Whitney test). Data points represent mean ± S.E.M from analysis of quadruplicates of each individual. Data from patients (n = 4) and controls (n = 2) were pooled respectively.</div>
|
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<p> Figure 3. Impaired TNFR signaling and deubiquitinase… </p>
|
||
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<p> Figure 3. Impaired TNFR signaling and deubiquitinase function of mutant TNFAIP3/A20 </p>
|
||
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|
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Figure 3. Impaired TNFR signaling and deubiquitinase function of mutant TNFAIP3/A20
|
||
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|
||
|
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|
||
<div class="figure-caption-contents">(<b>a</b>) Reduced recruitment of mutant A20 to the TNFR signaling complex. PBMCs from patient P4 and a healthy control were stimulated with TNF for the indicated times. Whole cell lysates were immunoprecipitated with antibodies against TNFR1, TRAF2, or RIP1, blotted with antibodies against N-terminal A20 and re-blotted with antibodies against TNFR1, TRAF2, RIP1 and Ubc13. (<b>b</b>-<b>d</b>) The A20 mutants lose their ability to deubiquitinate K63-ubiquitin chains but do not antagonize the deubiquitinase function of WT A20. 293T cells were transiently transfected with expression plasmids for A20 target proteins RIP1 with Myc tag (<b>b</b>), NEMO (<b>c</b>) and TRAF6 (<b>d</b>), together with plasmids for HA-K63Ub and either GFP-tagged WT or mutant A20. Cells were harvested 48 hrs later and an equal amount of whole cell lysates was immunoprecipitated with antibodies against respective target proteins. High-molecular weight (MW) Ub-aggregates (top panel) were indicated by immunoblotting of precipitates with a HA-specific antibody. As controls for transfection efficiency, cell lysates were also blotted with antibodies against each target protein (middle panel) or antibodies against the N-terminus of A20 or GFP tag (bottom panel). (<b>e-f</b>) TNF-stimulated patient PBMCs or fibroblasts showed increased levels and increased molecular weight of the K63-ubiquitinated NEMO protein as a result of insufficient A20 deubiquitinase activity. Primary cells from patients and healthy controls were stimulated for the indicated times. Whole cell lysates were subjected to immunoprecipitation with antibodies against K63-linked ubiquitin and subsequently blotted with antibodies against NEMO and Ub. Cell lysates were also blotted with antibodies against the target protein and β-actin as internal controls.</div>
|
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<p> Figure 4. Patients’ immune cells have a… </p>
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<p> Figure 4. Patients’ immune cells have a strong inflammatory signature </p>
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<div class="figure-caption-contents"><p> Cytokine profiles comparing A20-deficient patients… </p></div>
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Figure 4. Patients’ immune cells have a strong inflammatory signature
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<div class="figure-caption-contents">Cytokine profiles comparing A20-deficient patients with healthy controls. <b>(a)</b> Serum cytokine levels from 6 patients and 8 controls. <b>(b)</b> Cytokine levels from patients (n = 5) or controls (n = 6) PBMCs stimulated either with bacterial lipopolysaccharide (LPS) or Staphylococcal enterotoxin B (SEB). Each sample was assessed in duplicates or triplicates. Values are represented as mean ± S.E.M. (<b>c</b>) Representative flow plots of CD3+ CD4+ CD45RO+ single live cells: Upper panels show IL-9 expression by intra-cellular cytokine (ICC) staining. The A20-deficient patients (n = 4) expressed significantly more IL-9 compared to paired controls (n = 5), and <i>ex vivo</i> PU.1 transcript levels were likewise significantly increased in patient PBMCs. Lower panels show representative flow plots of IL-17A and IL-4 expression in an A20-deficient patient compared to a paired control. A significant increase in intracellular IL-17A expression was observed in patients (n = 5) compared to controls (n = 8). Consistent with an absence of clinical allergic disease, no significant difference in intracellular IL-4 was seen. * P<0.05; Mann-Whitney test. Values are represented as mean ± S.E.M. (<b>d</b>) Increased inflammatory monocyte subsets in patients. Top panel: Representative flow-cytometry analysis of monocyte subsets in one control (left) and one A20-deficient patient (right). Three monocyte subsets are identified as CD14<sup>high</sup>CD16<sup>neg</sup> (classical, P1), CD14<sup>high</sup>CD16<sup>pos</sup> (inflammatory, P2), CD14<sup>low</sup>CD16<sup>pos</sup> (non-classical, P3). The population (%) of different subsets is shown in different gates. Bottom panel: Quantification of CD14<sup>high</sup>CD16<sup>pos</sup> (inflammatory) monocyte subsets in 4 A20-deficient patients and in 4 controls. Data are shown as mean ± SD (<i>p</i> = 0.00013, n = 4).</div>
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<p> Figure 5. Spontaneous NLRP3 inflammasome activity in… </p>
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<strong class="figure-label">
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<p> Figure 5. Spontaneous NLRP3 inflammasome activity in PBMCs of patients with <i> TNFAIP3 </i> mutations </p>
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<div class="figure-caption-contents"><p> ( <b> a… </b> </p></div>
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Figure 5. Spontaneous NLRP3 inflammasome activity in PBMCs of patients with <i>TNFAIP3</i> mutations
|
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</strong>
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|
||
<div class="figure-caption-contents">(<b>a</b>) Immunoblots of total cell lysates from LPS-stimulated patient cells and control show increased expression of pro IL-1β, NLRP3 and activated Caspase-1 (p10) and increased production of mature IL-1β. (<b>b</b>) IL-1β secretion in supernatants of LPS-stimulated patient cells is regulated by the activity of the NLRP3 inflammasome. Activation of adenylate cyclase (NKH477: adenylate cyclase activator), a PLC inhibitor (U73122), and a small molecule MCC950 attenuate the NLRP3 inflammasome activation. U73343: inactive analog of U73122. (<b>c</b>) Treatment with an IL-1 inhibitor, anakinra, normalized markers of systemic inflammation in Patient 6. Anakinra was initially given at a dose of 200mg daily (2014 May), later increased to 400mg daily (2014 Jun-2014 Sep), and then increased to 500 mg daily (2014 Oct-2015 Aug). The patient was also on prednisone 10mg and azathioprine 200 mg daily. Besides anakinra, she had no other medication changes from 2012-2014.</div>
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Ma CA, et al. Dendritic cells from humans with hypomorphic mutations in IKBKG/NEMO have impaired mitogen-activated protein kinase activity. Human mutation. 2011;32:318–24.
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-
|
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<a
|
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class="reference-link"
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|
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TNF Receptor-Associated Factor 6 / metabolism
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Tumor Necrosis Factor alpha-Induced Protein 3
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</div>
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<div id="substances" class="substances keywords-section">
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<h2 class="title">
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Substances
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</h2>
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword AGFG1 protein, human"
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AGFG1 protein, human
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aria-label="Dropdown menu for keyword AGFG1 protein, human"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword DNA-Binding Proteins"
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DNA-Binding Proteins
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|
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aria-label="Dropdown menu for keyword DNA-Binding Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in PubMed
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword I-kappa B Proteins"
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tabindex="0"
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I-kappa B Proteins
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</button><div id="keyword-actions-substances-2"
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hidden
|
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aria-label="Dropdown menu for keyword I-kappa B Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22I-kappa+B+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="I-kappa B Proteins"[nm]"
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Search in PubMed
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword IKBKG protein, human"
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|
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IKBKG protein, human
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Intracellular Signaling Peptides and Proteins"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Intracellular Signaling Peptides and Proteins
|
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</button><div id="keyword-actions-substances-4"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Intracellular Signaling Peptides and Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword NF-kappa B"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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NF-kappa B
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</button><div id="keyword-actions-substances-5"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword NF-kappa B"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword NFKBIA protein, human"
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tabindex="0"
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data-pinger-ignore>
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NFKBIA protein, human
|
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hidden
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aria-label="Dropdown menu for keyword NFKBIA protein, human"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in PubMed
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Search in MeSH
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Nuclear Pore Complex Proteins"
|
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tabindex="0"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Nuclear Pore Complex Proteins
|
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</button><div id="keyword-actions-substances-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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Nuclear Proteins
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RNA-Binding Proteins
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|
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</div>
|
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||
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||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div id="related-links" class="related-links">
|
||
<h2 class="title">
|
||
Related information
|
||
</h2>
|
||
|
||
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=26642243"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=1">
|
||
Cited in Books
|
||
</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=2">
|
||
ClinVar
|
||
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=3">
|
||
Gene
|
||
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=4">
|
||
Gene (GeneRIF)
|
||
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=5">
|
||
MedGen
|
||
</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=6">
|
||
MedGen (Bookshelf cited)
|
||
</a></li><li><a title="OMIM (cited) Links" href="https://www.ncbi.nlm.nih.gov/omim?linkname=pubmed_omim_cited&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=7">
|
||
OMIM (cited)
|
||
</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=8">
|
||
Protein
|
||
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=9">
|
||
Protein (RefSeq)
|
||
</a></li><li><a title="PubMed to SNP links" href="https://www.ncbi.nlm.nih.gov/snp?linkname=pubmed_snp&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=10">
|
||
SNP
|
||
</a></li><li><a title="Related dbGaP record" href="https://www.ncbi.nlm.nih.gov/gap?linkname=pubmed_gap&from_uid=26642243"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26642243&ordinalpos=1&linkpos=11">
|
||
dbGaP
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="grants" class="grants">
|
||
<h2 class="title">
|
||
Grants and funding
|
||
</h2>
|
||
<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
||
title="All articles for grant K23 AR068440/AR/NIAMS NIH HHS/United States"
|
||
href="/?term=K23+AR068440%2FAR%2FNIAMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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K23 AR068440/AR/NIAMS NIH HHS/United States
|
||
</a></li><li class="grant-item"><a
|
||
title="All articles for grant Z99 HG999999/Intramural NIH HHS/United States"
|
||
href="/?term=Z99+HG999999%2FIntramural+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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Z99 HG999999/Intramural NIH HHS/United States
|
||
</a></li></ul></div>
|
||
</div>
|
||
|
||
|
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