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<meta name="description" content="The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe …"><meta name="keywords" content="pmid:11810107, PMC2606053, doi:10.1038/ng832, Research Support, Non-U.S. Gov&#x27;t, Research Support, U.S. Gov&#x27;t, P.H.S., Sergey Kalachikov, Oleg Evgrafov, T Conrad Gilliam, Animals, Auditory Diseases, Central / complications, Auditory Diseases, Central / genetics*, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 10, DNA, Epilepsy / complications, Epilepsy / genetics*, Female, Genes, Dominant*, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Mutation*, Pedigree, Proteins / genetics*, Reverse Transcriptase Polymerase Chain Reaction, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/11810107/"><meta property="og:description" content="The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/11810107/"><meta name="twitter:description" content="The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl">
<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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl">
<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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl">
<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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl">
<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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl">
<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="11810107">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1038/ng832"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3094&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=11810107&amp;db=pubmed&amp;nlmid=9216904"
title="See full text options at Nature Publishing Group"
data-ga-category="full_text"
data-ga-action="Nature Publishing Group"
data-ga-label="11810107"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="Nature Publishing Group full text link"><span class="text">
Nature Publishing Group
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/11810107/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=11810107&amp;db=pubmed&amp;nlmid=9216904"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="11810107"
><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="/11810107/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/11810107/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="11810107" 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%2F11810107%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="efGKUG65UIbRuAGt6bOdrZK04HoK1Zo1v2qPxwzrujYlo1MjJurfV7gECL6WUAWl"><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"
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The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies.
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<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Transcript map of the genetically… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Transcript map of the genetically defined interval for ADPEAF on chromosome 10q24. The… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 1
</strong>
<div class="figure-caption-contents">Transcript map of the genetically defined interval for ADPEAF on chromosome 10q24. The minimal genetic region believed to harbor the ADPEAF gene is shown. <b><i>a</i></b>,<b><i>b</i></b>, The speckled bars denote minimal genetic regions defined by the linkage studies of Ottman <i>et al</i>. (<i>a</i>; top bar) and Poza <i>et al</i>. (<i>b</i>; bottom bar). The 3-cM region of overlap was flanked by locus <i>D10S200</i> on the centromeric boundary and by <i>D10S577</i> at the telomeric boundary. Radiation hybrid mapping analysis predicted that the interval would span 16 cR, which corresponds to 4 Mb on human chromosome 10. Physical mapping further refined the region to 4.2 Mb. <b><i>c</i></b>, A transcript map of the region constructed by combining data from Human Gene Map 99 from NCBI with basic local alignment search tool predictions generated by comparison of 10q24 genomic DNA with the dbEST database. A total of 47 independent ESTs were identified, 28 of which contained unambiguous ORFs. These putative genes are listed in red, and microsatellite markers in black. Arrows indicate the direction of transcription. Black arrows indicate that the candidate gene was screened for ADPEAF-related mutations. <i>SLIT1</i>, a gene with a gene structure and expression similar to that of <i>LGI1</i>, is located in the interval approximately 3.2 Mb telomeric to <i>LGI1</i>.</div>
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<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Segregation of putative disease alleles… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
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<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Segregation of putative disease alleles in families with ADPEAF. Family 6610 is the… </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Fig. 2
</strong>
<div class="figure-caption-contents">Segregation of putative disease alleles in families with ADPEAF. Family 6610 is the original family used to establish linkage between 10q24 DNA markers and disease. Filled bars mark the presence and boundaries of disease-related haplotypes, defined in families A, B and C by markers <i>D10S185, D10S200, D10S198, D10S603, D10S192, D10S222</i> and <i>D10S566</i>, and in family 6610 by these markers excluding <i>D10S192</i>. The markers span a sex-averaged distance of 10.8 cM, according to the Marshfield map. Individuals who did not carry mutations are denoted by +/+, and those who carried one mutant and one normal allele by M/+. Original sequence tracings used to detect putative disease alleles are shown to the right of each family pedigree. Variant alleles are denoted by red arrows. Families 6610, A and B had insertion or deletion mutations, and the sequence traces show signatures characteristic of heterozygous changes by which the diploid sequences became asynchronous, beginning with the mutant nucleotide. To be certain of the actual mutation, <i>LGI1</i> DNA was subcloned and sequenced as haploid DNA from each of the families, and haploid cell lines were derived for family 6610 (GMP Companies; data not shown). Filled symbols represent individuals with idiopathic epilepsy; symbols containing a ? represent individuals classified as unknown, either because they had symptomatic epilepsy (sympt. epil.), febrile seizures (febrile sz.), alcohol-related acute symptomatic seizures (alcohol-related sz.) or isolated unprovoked seizure (isol. unprov. sz.), because they were under 20 y at the time of clinical assessment or because their final diagnosis was possible (rather than definite) epilepsy (poss. epil.). A detailed clinical description of each family has been presented separately,,.</div>
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<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Predicted effect of ADPEAF mutations… </p></div>
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</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Predicted effect of ADPEAF mutations on Lgi1. <b> <i> a </i> </b> , Structural organization of <i> LGI1.… </i> </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 3
</strong>
<div class="figure-caption-contents">Predicted effect of ADPEAF mutations on Lgi1. <b><i>a</i></b>, Structural organization of <i>LGI1. LGI1</i> spans 36.9 kb and consists of eight exons ranging in size from 72 bp (exons 25) to 1,197 bp (exon 8). The mRNA transcript consists of a 262-bp 3 UTR and a 1,674-bp ORF. Exon 1 includes a signal peptide, and exons 35 each contain a full 24-aa LRR motif (spanning from the fifth amino acid of one repeat to the fifth amino acid of the next). Putative mutations are illustrated by their corresponding family identifiers. Three were located in exon 8, one in exon 6 and one (from family B) in the 95-bp intron between exons 3 and 4. <b><i>b</i></b>, Predicted sequence motifs in Lgi1. This figure is a modification of those previously presented,. Beginning at the amino terminus (left), the protein contained a predicted signal peptide (filled arrow; positions 135), an N-terminal cysteine-rich LRR flanking sequence (LRRNT; residues 4571), three LRR repeat sequences (orange boxes; residues 90113, 114137 and 138161), a C-terminal cysteine-rich LRR flanking sequence (LRRCT; residues 173222), two direct repeat sequences (Rep1 and 2; residues 226361 and 420549, respectively) and a putative membrane-spanning segment (yellow rectangle). A 22-bp transmembrane region (residues 288309) was previously reported. We found support for this prediction using several methods, including the dense alignment surface (DAS) method for predicting integral membrane proteins,, although other methods (PRED-TMR) fail to predict the region. A fourth putative LRR repeat, predicted by Sommerville <i>et al</i>., resided N-terminally to the other three repeats and was encoded by exon 2. Although it seemed to share a common origin with the other repeats, its divergence at canonical residues made its role as a functional LRR repeat ambiguous. Chernova <i>et al</i>. predicted two potential N-glycosylation sites at Asn192 and Asn277 and potential phosphorylation sites for cAMP-dependent protein kinase (Ser 313), tyrosine kinase (Tyr 384) and several sites for PKC and casein kinase II. Lgi1 is predicted to consist of 557 amino-acid residues and to encode a slightly alkaline 60-kD protein (after removal of the signal peptide). <b><i>c</i></b>, Predicted effect of mutations on protein sequence. The predicted effect of each of the five presumptive ADPEAF mutations is depicted relative to the normal protein shown to encode 557 amino-acid residues. The singlebase pair insertion in family 6610 would predictably encode an Lgi1 protein with a normal complement of the first N-terminal 546 amino acids, followed by seven missense residues and four truncated residues. The Lgi1 extracellular region and the C-terminal region were highly conserved between human and mouse. Likewise, the frameshift mutations in families A and C would predictably alter protein structure and function dramatically. Family B showed a C→A transversion at position 3 relative to the exon 4 acceptor splice site. Whereas positions 1 and 2 are typically conserved and often lead to cryptic site usage or exon skipping when altered, little is known about the effects of alteration at the 3 position. The presumptive mutation led to retention of intron 3 in a portion of <i>LGI1</i> transcripts from affected individuals (Fig. 4). Family D showed a non-conservative missense mutation in exon 8.</div>
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itemprop="contentUrl"
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Aberrant <i> LGI1 </i> splicing in family… </p></div>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Aberrant <i> LGI1 </i> splicing in family B. <b> <i> a </i> </b> , <i> LGI1 </i> oligonucleotide primers specific for… </p></div>
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Fig. 4
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<div class="figure-caption-contents">Aberrant <i>LGI1</i> splicing in family B. <b><i>a</i></b>, <i>LGI1</i> oligonucleotide primers specific for exon 3 and exon 6 were amplified using RTPCR and mRNA isolated from lymphoblastoid cell lines. Lane 1, control sample; lanes 25, samples from four affected individuals in family B; lane 6, 100-bp size standards. All sample lanes showed a 286-bp fragment corresponding to the normal transcript. Samples from affected individuals also showed a second band that included a 72-bp insertion corresponding to the intact intron 3. <b><i>b</i></b>, Alignment of DNA sequencing traces corresponding to genomic DNA from a control individual (top panel) and an individual from family B with epilepsy (middle panel), together with the sequence trace corresponding to the aberrant RTPCR fragment (bottom panel) derived from the same cell line represented in the middle panel. As expected, the genomic trace from the individual with epilepsy showed a C/A heterozygote at IVS3(3), whereas the aberrant RTPCR fragment contained exclusively adenine at the same position. <b><i>c</i></b>, Sequence alignment of the aberrant (top) and normal (bottom) <i>LGI1</i> amplification fragments. A complete copy of intron 3 was retained in the aberrant transcript, introducing a putative stop codon (blue type) at the start of intron 3. The presumptive splice-site mutation is shown in red.</div>
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<p> Fig. 5 </p>
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<div class="figure-caption-contents"><p> Analysis of <i> Lgi1 </i> expression in… </p></div>
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<p> Fig. 5 </p>
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<div class="figure-caption-contents"><p> Analysis of <i> Lgi1 </i> expression in the adult mouse brain by chromogenic RNA <i> in… </i> </p></div>
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Fig. 5
</strong>
<div class="figure-caption-contents">Analysis of <i>Lgi1</i> expression in the adult mouse brain by chromogenic RNA <i>in situ</i> hybridization. <b><i>a</i></b><b><i>c</i></b>,<b><i>f</i></b>, An antisense riboprobe (<i>a</i><i>c</i>) or a sense (control) riboprobe (<i>f</i>) of <i>Lgi1</i> was hybridized to 16-μm thin coronal cryosections of brains harvested from 10-wk mice (see Methods). Shown are representative sections from the anterior to the posterior extent of the temporal cortex (×40). Bregma values refer to the classical coordinates for vertebrate sections along the anteriorposterior axis. In <i>a</i>, the arrow marks the piriform cortex; in <i>b</i>, the open arrow marks the amygdala and the closed arrows the CA3 region and the dentate gyrus of the hippocampal formation. In <i>c</i>, the arrow marks the location of the mouse auditory cortex. As seen in the low-power images of <i>a</i><i>c</i>, <i>Lgi1</i> was expressed more in ventral cortical structures than dorsal structures. Careful inspection of these sections, however, revealed <i>Lgi1</i>-expressing cells in distinct areas of the dorsal cortex. <b><i>d</i></b>,<b><i>e</i></b>, Brain maps of the piriform cortex (<i>d</i>) and the dentate gyrus and amygdala (<i>e</i>). <b><i>g</i></b><b><i>i</i></b>, Enlargements of <i>Lgi1</i> expression in the piriform cortex, dentate gyrus and amygdala, respectively (×200). The relative location of each of these brain regions is identified by rectangular boxes on the brain maps depicted in <i>d</i> and <i>e</i>. Stars in <i>g</i><i>i</i> denote molecular areas or fiber tracts that seemed to be generally devoid of <i>Lgi1</i>-expressing cells, whereas areas that were densely packed with neurons demonstrated high <i>Lgi1</i> expression (arrows in <i>g</i><i>i</i>). This restricted expression of <i>Lgi1</i> was especially apparent in the hippocampal formation (<i>h</i>). Here <i>Lgi1</i> expression was constrained to the granular cells of the dentate gyrus (closed arrows), to large-bodied cells within the hilus of the dentate gyrus (open arrows) and to the pyramidal cells of the CA3 region (solid arrows) but was absent from the molecular areas (stars in <i>h</i>). The <i>in situ</i> analysis also revealed the presence of distinct mRNA levels in individual cells in both the piriform cortex (<i>g</i>) and amygdala (<i>i</i>). Cells within the basolateral nuclei of the amygdala (BLP, basolateral amygdala posterior; BLA, basolateral amygdala anterior) seemed to express distinctly larger amounts of <i>Lgi1</i> than did cells within the lateral nuclei of the amygdala (LA in <i>i</i>).</div>
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MeSH terms
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</div>
<div id="substances" class="substances keywords-section">
<h2 class="title">
Substances
</h2>
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DNA
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</div>
<div id="related-links" class="related-links">
<h2 class="title">
Related information
</h2>
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=1">
Cited in Books
</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=2">
ClinVar
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=3">
Gene
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=4">
Gene (GeneRIF)
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=5">
MedGen
</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=6">
MedGen (Bookshelf cited)
</a></li><li><a title="Related information in MedGen (OMIM)" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_omim&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=7">
MedGen (OMIM)
</a></li><li><a title="Published Nucleotide sequences" href="https://www.ncbi.nlm.nih.gov/nuccore?linkname=pubmed_nuccore&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=8">
Nucleotide
</a></li><li><a title="OMIM (cited) Links" href="https://www.ncbi.nlm.nih.gov/omim?linkname=pubmed_omim_cited&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=9">
OMIM (cited)
</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=10">
Protein
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=11">
Protein (RefSeq)
</a></li><li><a title="Related PubChem Compound via MeSH" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound_mesh&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=12">
PubChem Compound (MeSH Keyword)
</a></li><li><a title="PubMed to SNP links" href="https://www.ncbi.nlm.nih.gov/snp?linkname=pubmed_snp&amp;from_uid=11810107"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=11810107&ordinalpos=1&linkpos=13">
SNP
</a></li></ul>
</div>
<div id="grants" class="grants">
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