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<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="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN">
<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="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN">
<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="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
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<aside class="page-sidebar">
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<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://www.neurology.org/doi/10.1212/WNL.0000000000001315?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
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target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25653295&amp;db=pubmed&amp;nlmid=0401060"
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Free PMC article
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<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="/25653295/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/25653295/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="25653295" 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%2F25653295%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="t5QCwL3mAIyKDyO4NrL8oHzRVSgkPMdtKSAH9BwIajlexZUUqKoaSP5vtWYwInLN"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
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"
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<h1 class="heading-title">
Differential effects of severe vs mild GBA mutations on Parkinson disease
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<div class="publication-type" >Meta-Analysis</div>
<h1 class="heading-title">
Differential effects of severe vs mild GBA mutations on Parkinson disease
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<span class="authors-list-item "><span class="full-name">Ziv Gan-Or</span><span class="citation-separator">&nbsp;et al.</span></span>
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<span class="authors-list-item "><a class="full-name"
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data-ga-label="Ziv Gan-Or">Ziv Gan-Or</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada. aviorr@tasmc.health.gov.il ziv.gan-or@mail.mcgill.ca." href="#short-view-affiliation-1" ref="linksrc=author_aff">
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data-ga-label="Idan Amshalom">Idan Amshalom</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Laura L Kilarski">Laura L Kilarski</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Anat Bar-Shira">Anat Bar-Shira</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Karen Marder">Karen Marder</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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data-ga-label="Susan Bressman">Susan Bressman</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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data-ga-label="Nir Giladi">Nir Giladi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada." href="#short-view-affiliation-2" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Avi Orr-Urtreger">Avi Orr-Urtreger</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada. aviorr@tasmc.health.gov.il ziv.gan-or@mail.mcgill.ca." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
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><sup class="key">1</sup> From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada. aviorr@tasmc.health.gov.il ziv.gan-or@mail.mcgill.ca.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> From The Genetic Institute (Z.G.-O., I.A., A.B.-S., M.G.-W., A.O.-R.) and Movement Disorders Unit, Parkinson Center, and Department of Neurology (A.M., N.G.), Tel Aviv Sourasky Medical Center; The Sackler Faculty of Medicine (N.G., A.O.-U.), Tel Aviv University, Israel; Stroke and Dementia Research Centre (L.L.K.), St. George&#x27;s, University of London, UK; Columbia University (K.M.), Columbia Presbyterian Medical Center, New York; and Beth Israel Medical Center (S.B.), New York, NY. Z.G.-O. is currently affiliated with the Department of Human Genetics and Montreal Neurological Institute, McGill University, Montreal, Canada.</li>
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<p>
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Objective:
</strong>
To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD).
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Methods:
</strong>
We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results.
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Results:
</strong>
Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p &lt; 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p &lt; 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)).
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Conclusions:
</strong>
These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up.
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<p> Figure 1. Meta-analysis of severe and mild… </p>
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<p> Figure 1. Meta-analysis of severe and mild <i> GBA </i> mutations and Parkinson disease risk </p>
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Figure 1. Meta-analysis of severe and mild <i>GBA</i> mutations and Parkinson disease risk
</strong>
<div class="figure-caption-contents">(A) Forest plot of studies with data on mild <i>GBA</i> mutations, using an empirical continuity correction (see methods) for studies with zero cases with mild <i>GBA</i> mutations. The analysis included data from 31 studies with a total of 11,453 cases and 14,565 controls. The <i>p</i> value for heterogeneity was 0.62. (B) Forest plot of studies with data on severe <i>GBA</i> mutations, using an empirical continuity correction (see methods) for studies with zero cases with severe <i>GBA</i> mutations. The analysis included data from 31 studies with a total of 11,453 cases and 14,565 controls. The <i>p</i> value for heterogeneity was 0.94. FE = fixed effect; Ref = reference number.</div>
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<div id="substances" class="substances keywords-section">
<h2 class="title">
Substances
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Related information
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Gene
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Gene (GeneRIF)
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