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</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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ">
<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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ">
<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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ">
<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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ">
<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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="30237576">
<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)01042-X"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=30237576&amp;db=pubmed&amp;nlmid=9815831"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="30237576"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/30237576/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=30237576&amp;db=pubmed&amp;nlmid=9815831"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="30237576"
><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="/30237576/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/30237576/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="30237576" 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%2F30237576%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="Oij4vwbsAKWxuKMJYLKuGMiJTNf2FIcp55398mEOalJ1obSzB4nwaUOnrRXeyjKJ"><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"
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<h1 class="heading-title">
Autozygome and high throughput confirmation of disease genes candidacy
</h1>
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data-ga-label="Wesam Kurdi">Wesam Kurdi</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia." href="#full-view-affiliation-15" ref="linksrc=author_aff">
15
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia." href="#full-view-affiliation-16" ref="linksrc=author_aff">
16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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15
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Saeed M Al Tala">Saeed M Al Tala</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Armed Forces Hospital SR, Khamis Mushayt, Saudi Arabia." href="#full-view-affiliation-17" ref="linksrc=author_aff">
17
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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18
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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18
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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19
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Brahim Tabarki">Brahim Tabarki</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia." href="#full-view-affiliation-6" ref="linksrc=author_aff">
6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia." href="#full-view-affiliation-20" ref="linksrc=author_aff">
20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia." href="#full-view-affiliation-20" ref="linksrc=author_aff">
20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Saad AlShahwan">Saad AlShahwan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia." href="#full-view-affiliation-6" ref="linksrc=author_aff">
6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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21
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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22
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Dorota Monies">Dorota Monies</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia." href="#full-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia." href="#full-view-affiliation-20" ref="linksrc=author_aff">
20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Fowzan S Alkuraya">Fowzan S Alkuraya</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#full-view-affiliation-23" ref="linksrc=author_aff">
23
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#full-view-affiliation-24" ref="linksrc=author_aff">
24
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#full-view-affiliation-25" ref="linksrc=author_aff">
25
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#full-view-affiliation-26" ref="linksrc=author_aff">
26
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<h3 class="title">
Affiliations
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<ul class="item-list">
<li data-affiliation-id="full-view-affiliation-1"
id="full-view-affiliation-1"
><sup class="key">1</sup> Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-2"
id="full-view-affiliation-2"
><sup class="key">2</sup> Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-3"
id="full-view-affiliation-3"
><sup class="key">3</sup> College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-4"
id="full-view-affiliation-4"
><sup class="key">4</sup> Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-5"
id="full-view-affiliation-5"
><sup class="key">5</sup> Department of Pediatrics, King Faisal Specialist hospital and Research Center, Jeddah, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-6"
id="full-view-affiliation-6"
><sup class="key">6</sup> Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-7"
id="full-view-affiliation-7"
><sup class="key">7</sup> Genetic Unit, Children&#x27;s Hospital, King Saud Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-8"
id="full-view-affiliation-8"
><sup class="key">8</sup> Department of Pediatrics, Children&#x27;s Hospital, Ain Shams University, Cairo, Egypt.</li>
<li data-affiliation-id="full-view-affiliation-9"
id="full-view-affiliation-9"
><sup class="key">9</sup> Department of Pediatrics, Dr. Suliman Al Habib Medical Group, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-10"
id="full-view-affiliation-10"
><sup class="key">10</sup> Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-11"
id="full-view-affiliation-11"
><sup class="key">11</sup> Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Doha, Doha, Qatar.</li>
<li data-affiliation-id="full-view-affiliation-12"
id="full-view-affiliation-12"
><sup class="key">12</sup> Genetics Division, Department of Pediatrics, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-13"
id="full-view-affiliation-13"
><sup class="key">13</sup> Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-14"
id="full-view-affiliation-14"
><sup class="key">14</sup> Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-15"
id="full-view-affiliation-15"
><sup class="key">15</sup> Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-16"
id="full-view-affiliation-16"
><sup class="key">16</sup> Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-17"
id="full-view-affiliation-17"
><sup class="key">17</sup> Department of Pediatrics, Armed Forces Hospital SR, Khamis Mushayt, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-18"
id="full-view-affiliation-18"
><sup class="key">18</sup> Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-19"
id="full-view-affiliation-19"
><sup class="key">19</sup> Department of pediatrics, King Abdulaziz Medical City, Jeddah, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-20"
id="full-view-affiliation-20"
><sup class="key">20</sup> Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-21"
id="full-view-affiliation-21"
><sup class="key">21</sup> Medical Genetic Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-22"
id="full-view-affiliation-22"
><sup class="key">22</sup> Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="full-view-affiliation-23"
id="full-view-affiliation-23"
><sup class="key">23</sup> Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="full-view-affiliation-24"
id="full-view-affiliation-24"
><sup class="key">24</sup> College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="full-view-affiliation-25"
id="full-view-affiliation-25"
><sup class="key">25</sup> Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="full-view-affiliation-26"
id="full-view-affiliation-26"
><sup class="key">26</sup> Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
</ul>
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Autozygome and high throughput confirmation of disease genes candidacy
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<span class="authors-list-item "><span class="full-name">Sateesh Maddirevula</span><span class="citation-separator">&nbsp;et al.</span></span>
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="College of Medicine, Alfaisal University, Riyadh, Saudi Arabia." href="#short-view-affiliation-3" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia." href="#short-view-affiliation-4" 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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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia." href="#short-view-affiliation-20" ref="linksrc=author_aff">
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1
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20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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21
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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22
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia." href="#short-view-affiliation-20" 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="Fowzan S Alkuraya">Fowzan S Alkuraya</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#short-view-affiliation-23" ref="linksrc=author_aff">
23
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#short-view-affiliation-24" ref="linksrc=author_aff">
24
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#short-view-affiliation-25" ref="linksrc=author_aff">
25
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa." href="#short-view-affiliation-26" ref="linksrc=author_aff">
26
</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> Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Department of Pediatrics, King Faisal Specialist hospital and Research Center, Jeddah, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Genetic Unit, Children&#x27;s Hospital, King Saud Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Department of Pediatrics, Children&#x27;s Hospital, Ain Shams University, Cairo, Egypt.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Department of Pediatrics, Dr. Suliman Al Habib Medical Group, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Doha, Doha, Qatar.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Genetics Division, Department of Pediatrics, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-15"
id="short-view-affiliation-15"
><sup class="key">15</sup> Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-16"
id="short-view-affiliation-16"
><sup class="key">16</sup> Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-17"
id="short-view-affiliation-17"
><sup class="key">17</sup> Department of Pediatrics, Armed Forces Hospital SR, Khamis Mushayt, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-18"
id="short-view-affiliation-18"
><sup class="key">18</sup> Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-19"
id="short-view-affiliation-19"
><sup class="key">19</sup> Department of pediatrics, King Abdulaziz Medical City, Jeddah, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-20"
id="short-view-affiliation-20"
><sup class="key">20</sup> Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-21"
id="short-view-affiliation-21"
><sup class="key">21</sup> Medical Genetic Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-22"
id="short-view-affiliation-22"
><sup class="key">22</sup> Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</li>
<li data-affiliation-id="short-view-affiliation-23"
id="short-view-affiliation-23"
><sup class="key">23</sup> Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="short-view-affiliation-24"
id="short-view-affiliation-24"
><sup class="key">24</sup> College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="short-view-affiliation-25"
id="short-view-affiliation-25"
><sup class="key">25</sup> Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
<li data-affiliation-id="short-view-affiliation-26"
id="short-view-affiliation-26"
><sup class="key">26</sup> Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.</li>
</ul>
</div>
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<h2 class="title">
Abstract
</h2>
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id="eng-abstract">
<p>
<strong class="sub-title">
Purpose:
</strong>
Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases.
</p>
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<strong class="sub-title">
Methods:
</strong>
Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders.
</p>
<p>
<strong class="sub-title">
Conclusions:
</strong>
Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing.
</p>
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<p>
<strong class="sub-title">
Keywords:
</strong>
ACMG guidelines; candidate genes; variant interpretation.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no conflicts of interest.</p>
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<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><b> Representative images of cases with… </b></div>
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<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><b> Representative images of cases with class 1 phenotypes. </b> <b> a </b> Panel of clinical images…</div>
</div>
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<strong class="figure-label">
Fig. 1
</strong>
<div class="figure-caption-contents"><b>Representative images of cases with class 1 phenotypes.</b>
<b>a</b> Panel of clinical images of the proband with <i>APC</i>-related CenaniLenz syndrome showing the classic bony syndactyly with loss of the normal configuration of the phalanges. <b>b</b> Brain magnetic resonance image (MRI) of the proband with pathogenic variant in <i>ACTL6B</i> showing agenesis of corpus callosum and mild ventricular dilatation (2.70cm). <b>c</b> Typical skeletal findings in the proband with <i>XRCC2</i>-related Fanconi anemia showing hypoplastic thumbs and dysplastic hips. <b>d</b> Brain MRI image showing thin but complete corpus callosum in the proband with <i>GOLGA2</i> pathogenic variant. <b>e</b> Clinical images of the proband with Steel syndrome (pathogenic variant in <i>COL27A1</i>) showing characteristic facial and skeletal appearance (elongated face with severe scoliosis). <b>f</b> Facial photograph and MRI brain of the proband with pathogenic variant in <i>CENPF</i> showing small head, relatively large ears, epicanthal folds, blue-tinged sclerae, prominent nose, thin upper lip, and small chin. MRI revealed reduced white matter volume and marginal pachygyria. <b>g</b> Brain MRI image showing mild molar tooth sign in the proband with KIAA0556 pathogenic variant. <b>h</b> Facial photographs of proband with <i>FUT8</i> pathogenic variant showing coarse face with synophrys, hypertelorism, sparse eye-lashes, low set ears, thick inverted V-shaped lips.</div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><b> Representative images of cases with… </b></div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><b> Representative images of cases with class 2 and 3 phenotypes. </b> <b> a </b> Clinical images…</div>
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Fig. 2
</strong>
<div class="figure-caption-contents"><b>Representative images of cases with class 2 and 3 phenotypes.</b>
<b>a</b> Clinical images of the proband with <i>TXNRD2</i> pathogenic variant showing dysmorphic facies and a large umbilical hernia. <b>b</b> The two siblings with <i>SCLT1</i> pathogenic variant showing absence of the anterior lobe of pituitary gland with the evidence of ectopia of the posterior pituitary gland and thalamic hamartoma. <b>c</b> Three families are with <i>CDK9</i>-related CHARGE-like phenotype showing cerebellar atrophy, unilateral choanal atresia, and dysplastic atrophic kidney. <b>d</b> Brain magnetic resonance image (MRI) of proband with pathogenic variant in <i>PARS2</i> showing severe cerebral volume loss indicating severe brain atrophy, thinning of the corpus callosum, and severe cerebral volume loss in the supratentorial and infratentorial area. <b>e</b> Clinical images of the proband with <i>PLOD3</i> pathogenic variant showing dysmorphic facies (prominent forehead, short and flat nose, ptosis with compensatory arching of eyebrows, posteriorly rotated low set ears) and hand contractures. <b>f</b> Facial features and MRI images of proband with <i>DMXL2</i> pathogenic variant represent long face, high forehead, short philtrum, low set ears, and moderate degree of cerebral and brainstem atrophy. <b>g</b> Brain MRI image showing small atrophic cerebellum with prominence of the posterior fossa cerebrospinal fluid (CSF) spaces in the proband with <i>GEMIN4</i> pathogenic variant. <b>h</b> Facial pictures of index (16DG0071) subject with <i>ABCA2</i> showing apparent lack of gross dysmorphism.</div>
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Wright CF, FitzPatrick DR, Firth HV. Paediatric genomics: diagnosing rare disease in children. Nat Rev Genet. 2018;19:253268. doi: 10.1038/nrg.2017.116.
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Wright Caroline F, McRae Jeremy F, Clayton Stephen, Gallone Giuseppe, Aitken Stuart, FitzGerald Tomas W, Jones Philip, Prigmore Elena, Rajan Diana, Lord Jenny, Sifrim Alejandro, Kelsell Rosemary, Parker Michael J, Barrett Jeffrey C, Hurles Matthew E, FitzPatrick David R, Firth Helen V. Making new genetic diagnoses with old data: iterative reanalysis and reporting from genome-wide data in 1,133 families with developmental disorders. Genetics in Medicine. 2018;20(10):12161223. doi: 10.1038/gim.2017.246.
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Nambot S, Thevenon J, Kuentz P, et al. Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis. Genet Med. 2017;20:645654. doi: 10.1038/gim.2017.162.
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