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|
||
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%2F25394172%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%2F25394172%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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
</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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
|
||
|
||
<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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
<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: 25394172 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 25394172"/>
|
||
<input type="hidden" name="email-subject-hash" value="585cc375cc4e000c81b97aa4ef2b1d4efcba269f16662aba8bc161c901c4c542"/>
|
||
</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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
|
||
|
||
<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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
|
||
|
||
<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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
<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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
|
||
|
||
<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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR">
|
||
|
||
<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="25394172">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S1098-3600(21)04854-1"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=25394172&db=pubmed&nlmid=9815831"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="25394172"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/25394172/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=25394172&db=pubmed&nlmid=9815831"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="25394172"
|
||
><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="/25394172/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/25394172/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="25394172" 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%2F25394172%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="yOFs2vS2PpCeyVNGl35eXIoRIimRRCoxPBpxFllop0pIsmTwYmIgrQUvgm43KdWR"><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
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><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"
|
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<h1 class="heading-title">
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Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations
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data-ga-label="Johanna Tommiska">Johanna Tommiska</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Biomedicine/Physiology, University of Helsinki and Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland." href="#full-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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href="/?term=Hu+Y&cauthor_id=25394172"
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data-ga-label="Youli Hu">Youli Hu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Centre for Neuroendocrinology, University College London Medical School, London, UK." href="#full-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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href="/?term=Tiosano+D&cauthor_id=25394172"
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data-ga-label="Dov Tiosano">Dov Tiosano</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel [2] Bruce Rappaport Faculty of Medicine, Institute of Technology, Haifa, Israel." href="#full-view-affiliation-9" ref="linksrc=author_aff">
|
||
9
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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href="/?term=Gerard+M&cauthor_id=25394172"
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data-ga-label="Marion Gerard">Marion Gerard</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Clinical Genetics, Hôpital Universitaire de la Côte de Nacre, Caen, France." href="#full-view-affiliation-10" ref="linksrc=author_aff">
|
||
10
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Juliane Leger">Juliane Leger</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France." href="#full-view-affiliation-11" ref="linksrc=author_aff">
|
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11
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Drouin-Garraud+V&cauthor_id=25394172"
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data-ga-label="Valérie Drouin-Garraud">Valérie Drouin-Garraud</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics, Rouen University Hospital, Rouen, France." href="#full-view-affiliation-12" ref="linksrc=author_aff">
|
||
12
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Lefebvre+H&cauthor_id=25394172"
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data-ga-label="Hervé Lefebvre">Hervé Lefebvre</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Endocrinology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France." href="#full-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=Polak+M&cauthor_id=25394172"
|
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data-ga-label="Michel Polak">Michel Polak</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Service d'Endocrinologie Gynécologie Diabétologie Pédiatriques, Hôpital Universitaire Necker Enfants Malades, University Paris Descartes, Paris, France." href="#full-view-affiliation-14" ref="linksrc=author_aff">
|
||
14
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Carel+JC&cauthor_id=25394172"
|
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data-ga-label="Jean-Claude Carel">Jean-Claude Carel</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France." href="#full-view-affiliation-11" ref="linksrc=author_aff">
|
||
11
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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href="/?term=Phan-Hug+F&cauthor_id=25394172"
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data-ga-label="Franziska Phan-Hug">Franziska Phan-Hug</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Endocrinology-Diabetology Unit, Department of Pediatrics, Lausanne University Hospital (CHUV), Lausanne, Switzerland." href="#full-view-affiliation-15" ref="linksrc=author_aff">
|
||
15
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Hauschild+M&cauthor_id=25394172"
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data-ga-label="Michael Hauschild">Michael Hauschild</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Endocrinology-Diabetology Unit, Department of Pediatrics, Lausanne University Hospital (CHUV), Lausanne, Switzerland." href="#full-view-affiliation-15" ref="linksrc=author_aff">
|
||
15
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Plummer+L&cauthor_id=25394172"
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data-ga-label="Lacey Plummer">Lacey Plummer</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA." href="#full-view-affiliation-16" ref="linksrc=author_aff">
|
||
16
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Rey+JP&cauthor_id=25394172"
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data-ga-label="Jean-Pierre Rey">Jean-Pierre Rey</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [2] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." href="#full-view-affiliation-17" ref="linksrc=author_aff">
|
||
17
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Raivio+T&cauthor_id=25394172"
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data-ga-label="Taneli Raivio">Taneli Raivio</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Biomedicine/Physiology, University of Helsinki and Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland." href="#full-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Bouloux+P&cauthor_id=25394172"
|
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data-ga-label="Pierre Bouloux">Pierre Bouloux</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Centre for Neuroendocrinology, University College London Medical School, London, UK." href="#full-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Sidis+Y&cauthor_id=25394172"
|
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data-ga-label="Yisrael Sidis">Yisrael Sidis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." href="#full-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
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href="/?term=Mohammadi+M&cauthor_id=25394172"
|
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data-ga-label="Moosa Mohammadi">Moosa Mohammadi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA." href="#full-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=de+Roux+N&cauthor_id=25394172"
|
||
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|
||
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data-ga-label="Nicolas de Roux">Nicolas de Roux</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Laboratoire de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France." href="#full-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=Pitteloud+N&cauthor_id=25394172"
|
||
ref="linksrc=author_name_link"
|
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data-ga-label="Nelly Pitteloud">Nelly Pitteloud</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." href="#full-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</a></sup></span>
|
||
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|
||
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||
|
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Affiliations
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Affiliations
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><sup class="key">1</sup> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France.</li>
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><sup class="key">2</sup> 1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Pediatrics, Division of Pediatric Endocrinology, State University of New York Downstate Medical Center, Brooklyn, New York, USA.</li>
|
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|
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><sup class="key">3</sup> 1] Department of Endocrinology and Diabetes, Shanghai Huashan Hospital, Shanghai, China [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.</li>
|
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|
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|
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<li data-affiliation-id="full-view-affiliation-5"
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><sup class="key">5</sup> 1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.</li>
|
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|
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|
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|
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|
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|
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|
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|
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|
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<li data-affiliation-id="full-view-affiliation-10"
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><sup class="key">11</sup> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.</li>
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|
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|
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<li data-affiliation-id="full-view-affiliation-14"
|
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|
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|
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|
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|
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><sup class="key">18</sup> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Laboratoire de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.</li>
|
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Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations
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|
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data-ga-label="Jean-Pierre Rey">Jean-Pierre Rey</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [2] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." 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"
|
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href="/?term=Raivio+T&cauthor_id=25394172"
|
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data-ga-label="Taneli Raivio">Taneli Raivio</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Biomedicine/Physiology, University of Helsinki and Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland." 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"
|
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href="/?term=Bouloux+P&cauthor_id=25394172"
|
||
ref="linksrc=author_name_link"
|
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|
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data-ga-label="Pierre Bouloux">Pierre Bouloux</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Centre for Neuroendocrinology, University College London Medical School, London, UK." 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"
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data-ga-label="Yisrael Sidis">Yisrael Sidis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." href="#short-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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|
||
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data-ga-label="Moosa Mohammadi">Moosa Mohammadi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, 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"
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href="/?term=de+Roux+N&cauthor_id=25394172"
|
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data-ga-label="Nicolas de Roux">Nicolas de Roux</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Laboratoire de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France." 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=Pitteloud+N&cauthor_id=25394172"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
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||
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|
||
data-ga-label="Nelly Pitteloud">Nelly Pitteloud</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland." href="#short-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</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> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-2"
|
||
id="short-view-affiliation-2"
|
||
><sup class="key">2</sup> 1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Pediatrics, Division of Pediatric Endocrinology, State University of New York Downstate Medical Center, Brooklyn, New York, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-3"
|
||
id="short-view-affiliation-3"
|
||
><sup class="key">3</sup> 1] Department of Endocrinology and Diabetes, Shanghai Huashan Hospital, Shanghai, China [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-4"
|
||
id="short-view-affiliation-4"
|
||
><sup class="key">4</sup> Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-5"
|
||
id="short-view-affiliation-5"
|
||
><sup class="key">5</sup> 1] Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [3] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-6"
|
||
id="short-view-affiliation-6"
|
||
><sup class="key">6</sup> Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-7"
|
||
id="short-view-affiliation-7"
|
||
><sup class="key">7</sup> Institute of Biomedicine/Physiology, University of Helsinki and Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-8"
|
||
id="short-view-affiliation-8"
|
||
><sup class="key">8</sup> Centre for Neuroendocrinology, University College London Medical School, London, UK.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-9"
|
||
id="short-view-affiliation-9"
|
||
><sup class="key">9</sup> 1] Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel [2] Bruce Rappaport Faculty of Medicine, Institute of Technology, Haifa, Israel.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-10"
|
||
id="short-view-affiliation-10"
|
||
><sup class="key">10</sup> Clinical Genetics, Hôpital Universitaire de la Côte de Nacre, Caen, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-11"
|
||
id="short-view-affiliation-11"
|
||
><sup class="key">11</sup> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-12"
|
||
id="short-view-affiliation-12"
|
||
><sup class="key">12</sup> Department of Genetics, Rouen University Hospital, Rouen, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-13"
|
||
id="short-view-affiliation-13"
|
||
><sup class="key">13</sup> Department of Endocrinology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-14"
|
||
id="short-view-affiliation-14"
|
||
><sup class="key">14</sup> Service d'Endocrinologie Gynécologie Diabétologie Pédiatriques, Hôpital Universitaire Necker Enfants Malades, University Paris Descartes, Paris, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-15"
|
||
id="short-view-affiliation-15"
|
||
><sup class="key">15</sup> Endocrinology-Diabetology Unit, Department of Pediatrics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-16"
|
||
id="short-view-affiliation-16"
|
||
><sup class="key">16</sup> Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-17"
|
||
id="short-view-affiliation-17"
|
||
><sup class="key">17</sup> 1] Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), Lausanne, Switzerland [2] Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-18"
|
||
id="short-view-affiliation-18"
|
||
><sup class="key">18</sup> 1] Unité Mixte de Recherche 1141, Institut National de la Santé et de la Recherche Médicale, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France [3] Laboratoire de Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.</li>
|
||
|
||
</ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<ul class="identifiers" id="short-view-identifiers">
|
||
|
||
<li>
|
||
<span class="identifier pubmed">
|
||
<span class="id-label">
|
||
|
||
PMID:
|
||
|
||
</span>
|
||
|
||
|
||
<strong class="current-id" title="PubMed ID">25394172</strong>
|
||
|
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|
||
|
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</span>
|
||
|
||
</li>
|
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|
||
<li>
|
||
<span class="identifier pmc">
|
||
<span class="id-label">
|
||
|
||
PMCID:
|
||
|
||
</span>
|
||
|
||
|
||
<a class="id-link"
|
||
target="_blank"
|
||
rel="noopener"
|
||
ref="linksrc=article_id_link&article_id=PMC4430466&id_type=PMC"
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4430466/"
|
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|
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>
|
||
PMC4430466
|
||
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||
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||
</span>
|
||
|
||
</li>
|
||
|
||
<li>
|
||
<span class="identifier doi">
|
||
<span class="id-label">
|
||
|
||
DOI:
|
||
|
||
</span>
|
||
|
||
|
||
<a class="id-link"
|
||
target="_blank"
|
||
rel="noopener"
|
||
ref="linksrc=article_id_link&article_id=10.1038/gim.2014.166&id_type=DOI"
|
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href="https://doi.org/10.1038/gim.2014.166"
|
||
data-ga-category="full_text"
|
||
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|
||
>
|
||
10.1038/gim.2014.166
|
||
</a>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
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|
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|
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</header>
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<div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger"
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Full text links
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</span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div>
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||
<div class="abstract" id="abstract">
|
||
|
||
<h2 class="title">
|
||
Abstract
|
||
|
||
</h2>
|
||
|
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||
<div class="abstract-content selected"
|
||
id="eng-abstract">
|
||
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||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Purpose:
|
||
</strong>
|
||
|
||
Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Methods:
|
||
</strong>
|
||
|
||
We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions and/or functional assays.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Results:
|
||
</strong>
|
||
|
||
We identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2α to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Conclusion:
|
||
</strong>
|
||
|
||
FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
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||
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|
||
|
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|
||
|
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|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p class="disclaimer" id="disclaimer">
|
||
<a href="/disclaimer/" target="_blank" data-ga-category="literature_resources"
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data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a>
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|
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|
||
|
||
|
||
|
||
|
||
<div class="figures" id="figures">
|
||
<h2 class="title">
|
||
Figures
|
||
</h2>
|
||
|
||
<div class="figures-list" id="slides-container"
|
||
itemscope itemtype="http://schema.org/ImageGallery">
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||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="0"
|
||
data-label-slug="figure-1">
|
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<a class="figure-link"
|
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4949/4430466/ec83609c5051/nihms-638007-f0001.jpg"
|
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itemprop="contentUrl"
|
||
aria-describedby="figure-caption-0"
|
||
role="button"
|
||
data-image-width="697"
|
||
data-image-height="624"
|
||
data-image-alt="Figure 1"
|
||
data-pmc-id="PMC4430466"
|
||
data-figure-id="F1">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-0"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4949/4430466/3766b8c327a0/nihms-638007-f0001.gif"
|
||
alt="Figure 1" />
|
||
</a>
|
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|
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 1. <i> FGFR1 </i> mutations underlie CHH with… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
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|
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|
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|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
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|
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|
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|
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|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 1. <i> FGFR1 </i> mutations underlie CHH with SHFM </p>
|
||
</strong>
|
||
|
||
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<div class="figure-caption-contents"><b> (A) </b> Pedigrees of the 7 CHH and…</div>
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<strong class="figure-label">
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Figure 1. <i>FGFR1</i> mutations underlie CHH with SHFM
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</strong>
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<div class="figure-caption-contents"><b>(A)</b> Pedigrees of the 7 CHH and SHFM families with <i>FGFR1</i> mutations; probands are denoted by arrows, SB: stillborn, OB: olfactory bulbs. <sup>A</sup>: homozygous mutation. <b>(B)</b> Photographs and radiographs demonstrating severe skeletal anomalies of hands and feet among probands.</div>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4949/4430466/ae068f969b96/nihms-638007-f0002.gif"
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<strong class="figure-label">
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<p> Figure 2. <i> FGFR1 </i> mutations identified in probands… </p>
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<strong class="figure-label">
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<p> Figure 2. <i> FGFR1 </i> mutations identified in probands with CHH and SHFM </p>
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<div class="figure-caption-contents"><b> (A) </b> Schematic of FGFR1…</div>
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<strong class="figure-label">
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Figure 2. <i>FGFR1</i> mutations identified in probands with CHH and SHFM
|
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</strong>
|
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<div class="figure-caption-contents"><b>(A)</b> Schematic of FGFR1 showing the locations of all published <i>FGFR1</i> mutations associated with CHH (Kallmann syndrome or normosmic CHH, red circles), Hartsfield syndrome (blue squares), septo-optic-dysplasia (green triangles). SP: signal peptide, D1: immunoglobulin domain 1, AB: acid box domain, D2: immunoglobulin domain 2, D3: immunoglobulin domain 3, TM: transmembrane domain, F: FRS2α -binding domain, TKD: tyrosine kinase domain, stars: mutations described in this study. <b>(B)</b> FGFR1 mutations identified in probands with CHH and SHFM, all the substituted residues of missense mutations are conserved across vertebrates (cow, mouse, chicken, xenopus, and zebrafish) and in human FGFR2 (hFGFR2).</div>
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<p> Figure 3. The V429E substitution in FGFR1… </p>
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<p> Figure 3. The V429E substitution in FGFR1 impedes recruitment and phosphorylation of FRS2α and FGF2-induced… </p>
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<strong class="figure-label">
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Figure 3. The V429E substitution in FGFR1 impedes recruitment and phosphorylation of FRS2α and FGF2-induced MAPK signaling
|
||
</strong>
|
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||
|
||
<div class="figure-caption-contents"><b>(A)</b> Analysis of the impact of the V429E mutation based on the NMR structure of the FRS2 phosphotyrosine binding (PTB) domain in complex with the juxtamembrane (JM) region peptide of FGFR1. The FRS2 PTB domain and FGFR1 JM peptide are shown as purple and green ribbons respectively, and side chains of the V429 of FGFR1 and L62, M105, V112 of FRS2 are rendered in sticks. The molecular surfaces of L62, M105, and V112 of FRS2 PTB are also shown, to highlight their hydrophobic contacts with V429 of FGFR1. <b>(B</b>) The V429E FGFR1c mutant fails to phosphorylate FRS2 in cell based assay. BaF3 were transfected with lentiviral vectors expressing WT or V429E FGFR1c and FRS2 phosphorylation was assessed upon FGF1 treatment by western blotting using anti phospho-FRS2-α specific antibodies . WT: wild type; EV: empty vector. <b>(C)</b> Analysis of the impact of the V429E mutation on the ability of FGFR1 to recruit FRS2α . The assay was based on FGFR2 V430E, which is equivalent to FGFR1 V429E. Increasing concentrations of FGFR2CD<sup>WT</sup> and FGFR2CD<sup>V430E</sup> (carrying the equivalent mutation to FGFR1-V429E) ranging from 12.5 to 400 nM were passed over a CM5 chip onto which FRS2α had been immobilized. As representative of the full dataset, binding responses obtained for injections of 200 nM of FGFR2CD<sup>WT</sup> or FGFR2CD<sup>V430E</sup> are shown. The rising and falling parts of the wild type curve (blue) represent the association and dissociation phases, respectively, of FGFR2CD<sup>WT</sup>-FRS2α binding over time. At 200 nM, FGFR2CD<sup>WT</sup> exhibits maximal binding of 55 response units (blue), whereas FGFR2CD<sup>V430E</sup> shows negligible binding (red). According to a steady-state equilibrium analysis of the full data sets (not shown), FGFR2CD<sup>WT</sup> binds FRS2α with a K<sub>D</sub> of 320 nM, whereas the FGFR2CD<sup>V430E</sup> negligible binding to FRS2α. <b>(D)</b> The V429E mutation reduces the ability of FGFR1 to phosphorylate FRS2 on Y196 <i>in vitro</i>. FGFR2<sup>WT</sup> and FGFR2<sup>V430E</sup> mutant kinases were allowed to phosphorylate FRS2 fragment PTB<sup>9-200</sup> on Y196, a tyrosine phosphorylation site known to be required for Grb2 recruitment, at room temperature for 0, 1, 3, 5 10, 15, 20, 25, 30 minutes. Following tryptic digestion, samples were analyzed by Orbitrap mass spectrometry to quantify the phospho-Y196-containing tryptic peptide. FGFR2<sup>WT</sup> is shown in blue and FGFR2<sup>V430E</sup> is shown in red. <b>(E-F)</b> The V429E mutation is loss-of-function in the OCFRE reporter assay (FRS2α dependent MAPK signaling) and not different from WT in the NFAT reporter assay (FRS2α independent PLCγ /IP<sub>3</sub>/Ca<sup>2+</sup> signaling). Data shown represent the means ± S.E.M. of 3 experiments. FGFR1 WT is shown in blue, FGFR1<sup>V429E</sup> in red, empty vector in black. Relative to the maximal stimulation of WT (%), ** <i>p</i><0.001, NS: not significant. <b>(G)</b> Total abundance and maturation of recombinant FGFR1 proteins. COS-7 cells were transfected with FGFR1 constructs and the cell lysates were subjected to deglycosylation treatment followed by western blot analysis. PNGase-treated bands represent total protein abundance levels; 140kDa Endo H-treated bands represent the mature form while 100kDa Endo H-treated bands represent immature form of FGFR1. The experiment was performed three times, tested by Mann-Whitney test for statistic significance, no significant difference in overall expression and maturation index between WT and V429E. PNGase: Peptide N-Glycosidase F-treated; Endo H: endoglycosidase H-treated; WT: wild type; EV: empty vector. <b>(H)</b> Cell surface abundance of the transiently transfected FGFR1 mutant in COS-7 cells. Cell surface abundance levels were measured by a radiolabeled antibody binding assay and plotted as a percentage of wild type levels. The abundance level of cell surface expressed FGFR1<sup>V429E</sup> was significantly higher than FGFR1<sup>wt</sup>. Values shown are the means ± SEM of 3 experiments each performed in quadruplicate. The difference between the mutant and the wild type receptor expression was compared by Mann-Whitney test, * p<0.05.</div>
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Tsai PS, Gill JC. Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome. Nature clinical practice. Endocrinology & metabolism. 2006 Mar;2(3):160–171.
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Miraoui H, Dwyer AA, Sykiotis GP, et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. American journal of human genetics. 2013 May 2;92(5):725–743.
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+N.I.H.%2C+Extramural"
|
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Research Support, Non-U.S. Gov't
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</button><div id="keyword-actions-publication-types-1"
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href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc"
|
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</div>
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|
||
<div id="mesh-terms" class="mesh-terms keywords-section">
|
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<h2 class="title">
|
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MeSH terms
|
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|
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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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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Animals
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aria-label="Dropdown menu for keyword Animals"><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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Conserved Sequence
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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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Female
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Female"><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-expanded="false"
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data-pinger-ignore>
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Genetic Association Studies
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</button><div id="keyword-actions-mesh-terms-5"
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aria-label="Dropdown menu for keyword Genetic Association Studies"><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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Humans
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Humans"><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 major"
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data-pinger-ignore>
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Hypogonadism / congenital*
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data-pinger-ignore>
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Hypogonadism / genetics*
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Search in PubMed
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data-ga-action="add_to_search"
|
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data-ga-label=""Hypogonadism/genetics"[MAJR]"
|
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|
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|
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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 Hypogonadism / metabolism"
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aria-controls="keyword-actions-mesh-terms-9"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Hypogonadism / metabolism
|
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</button><div id="keyword-actions-mesh-terms-9"
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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 Hypogonadism / metabolism"><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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href="/?term=%22Hypogonadism%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Hypogonadism%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hypogonadism/metabolism"[MeSH]"
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|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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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 major"
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aria-label="Toggle dropdown menu for keyword Limb Deformities, Congenital / genetics*"
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Limb Deformities, Congenital / genetics*
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</button><div id="keyword-actions-mesh-terms-major-10"
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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 Limb Deformities, Congenital / genetics*"><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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href="/?term=%22Limb+Deformities%2C+Congenital%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Limb+Deformities%2C+Congenital%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Limb Deformities, Congenital/genetics"[MAJR]"
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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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Limb Deformities, Congenital / metabolism
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|
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hidden
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aria-label="Dropdown menu for keyword Limb Deformities, Congenital / metabolism"><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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href="/?term=%22Limb+Deformities%2C+Congenital%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Limb+Deformities%2C+Congenital%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Limb Deformities, Congenital/metabolism"[MeSH]"
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Limb+Deformities%2C+Congenital"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Limb Deformities, Congenital/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-label=""Limb Deformities, Congenital/metabolism"[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 MAP Kinase Signaling System"
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MAP Kinase Signaling System
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</button><div id="keyword-actions-mesh-terms-12"
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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 MAP Kinase Signaling System"><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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href="/?term=%22MAP+Kinase+Signaling+System%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22MAP+Kinase+Signaling+System%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="MAP Kinase Signaling System"[MeSH]"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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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 Male"
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Male
|
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</button><div id="keyword-actions-mesh-terms-13"
|
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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 Male"><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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href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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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 Membrane Proteins / metabolism"
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Membrane Proteins / metabolism
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</button><div id="keyword-actions-mesh-terms-14"
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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 Membrane Proteins / metabolism"><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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href="/?term=%22Membrane+Proteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Membrane+Proteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Membrane Proteins/metabolism"[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 Molecular Sequence Data"
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aria-expanded="false"
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Molecular Sequence Data
|
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</button><div id="keyword-actions-mesh-terms-15"
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hidden
|
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aria-label="Dropdown menu for keyword Molecular Sequence Data"><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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href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Molecular Sequence Data"[MeSH]"
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|
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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 major"
|
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aria-label="Toggle dropdown menu for keyword Mutation*"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-16"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Mutation*
|
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</button><div id="keyword-actions-mesh-terms-major-16"
|
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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 Mutation*"><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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href="/?term=%22Mutation%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Mutation%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Mutation"[MAJR]"
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data-search-term=""Mutation"[MAJR]"
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data-ga-label=""Mutation"[MAJR]"
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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 Pedigree"
|
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-17"
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aria-expanded="false"
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data-pinger-ignore>
|
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Pedigree
|
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</button><div id="keyword-actions-mesh-terms-17"
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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 Pedigree"><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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href="/?term=%22Pedigree%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Pedigree%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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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 Phosphorylation"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Phosphorylation
|
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</button><div id="keyword-actions-mesh-terms-18"
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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 Phosphorylation"><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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href="/?term=%22Phosphorylation%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Phosphorylation%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Phosphorylation"[MeSH]"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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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 major"
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aria-label="Toggle dropdown menu for keyword Receptor, Fibroblast Growth Factor, Type 1 / genetics*"
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tabindex="0"
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data-pinger-ignore>
|
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Receptor, Fibroblast Growth Factor, Type 1 / genetics*
|
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</button><div id="keyword-actions-mesh-terms-major-19"
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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 Receptor, Fibroblast Growth Factor, Type 1 / genetics*"><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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|
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<div id="supplementary-concepts" class="supplementary-concepts keywords-section">
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Supplementary concepts
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<div id="related-links" class="related-links">
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<h2 class="title">
|
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Related information
|
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</h2>
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<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=25394172"
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Cited in Books
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</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=25394172"
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ClinVar
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Gene
|
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</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=25394172"
|
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Gene (GeneRIF)
|
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</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=25394172"
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MedGen
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</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=25394172"
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MedGen (Bookshelf cited)
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OMIM (cited)
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</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=25394172"
|
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|
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Protein (RefSeq)
|
||
</a></li><li><a title="PubMed to SNP links" href="https://www.ncbi.nlm.nih.gov/snp?linkname=pubmed_snp&from_uid=25394172"
|
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|
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SNP
|
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</a></li></ul>
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</div>
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<div id="grants" class="grants">
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Grants and funding
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<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
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