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<meta name="description" content="Digenic Alport syndrome refers to the inheritance of pathogenic variants in &lt;i&gt;COL4A5&lt;/i&gt; plus &lt;i&gt;COL4A3&lt;/i&gt; or &lt;i&gt;COL4A4&lt;/i&gt; or in &lt;i&gt;COL4A3&lt;/i&gt; plus &lt;i&gt;COL4A4&lt;/i&gt; Where digenic Alport syndrome includes a pathogenic &lt;i&gt;COL4A5&lt;/i&gt; variant, the consequences depend on the sex of the affected individua …"><meta name="keywords" content="pmid:35675912, PMC9718039, doi:10.2215/CJN.03120322, Review, Judy Savige, Alessandra Renieri, Joel T Gibson, Autoantigens / genetics, Collagen Type IV / genetics, Female, Humans, Male, Mutation, Nephritis, Hereditary* / genetics, Nephritis, Hereditary* / pathology, Pedigree, Proteinuria, 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="Digenic Alport Syndrome - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/35675912/"><meta property="og:description" content="Digenic Alport syndrome refers to the inheritance of pathogenic variants in &lt;i&gt;COL4A5&lt;/i&gt; plus &lt;i&gt;COL4A3&lt;/i&gt; or &lt;i&gt;COL4A4&lt;/i&gt; or in &lt;i&gt;COL4A3&lt;/i&gt; plus &lt;i&gt;COL4A4&lt;/i&gt; Where digenic Alport syndrome includes a pathogenic &lt;i&gt;COL4A5&lt;/i&gt; variant, the consequences depend on the sex of the affected individua …"><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="Digenic Alport Syndrome - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/35675912/"><meta name="twitter:description" content="Digenic Alport syndrome refers to the inheritance of pathogenic variants in &lt;i&gt;COL4A5&lt;/i&gt; plus &lt;i&gt;COL4A3&lt;/i&gt; or &lt;i&gt;COL4A4&lt;/i&gt; or in &lt;i&gt;COL4A3&lt;/i&gt; plus &lt;i&gt;COL4A4&lt;/i&gt; Where digenic Alport syndrome includes a pathogenic &lt;i&gt;COL4A5&lt;/i&gt; variant, the consequences depend on the sex of the affected individua …"><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="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6">
<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="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6">
<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="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6">
<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="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6">
<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="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6">
<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="35675912">
<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/10.2215/CJN.03120322"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3159&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=35675912&amp;db=pubmed&amp;nlmid=101271570"
title="See full text options at Wolters Kluwer"
data-ga-category="full_text"
data-ga-action="Wolters Kluwer"
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><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--journals.lww.com-cjasn-PublishingImages-CJASN-30x120.png" alt="Wolters Kluwer full text link"><span class="text">
Wolters Kluwer
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/35675912/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=35675912&amp;db=pubmed&amp;nlmid=101271570"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="35675912"
><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="/35675912/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/35675912/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="35675912" 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%2F35675912%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="VvZj8h3EITKI5XgWrk8pSSjbZvRBDh3MciJoL7w0iuxcZomM4DLrm0PPxzzNwSB6"><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"
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<h1 class="heading-title">
Digenic Alport Syndrome
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Digenic Alport Syndrome
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Correction: Digenic Alport Syndrome.
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<span class="docsum-journal-citation full-journal-citation">Clin J Am Soc Nephrol. 2023 Apr 1;18(4):511. doi: 10.2215/CJN.0000000000000096.</span>
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Digenic Alport syndrome refers to the inheritance of pathogenic variants in <i>COL4A5</i> plus <i>COL4A3</i> or <i>COL4A4</i> or in <i>COL4A3</i> plus <i>COL4A4</i> Where digenic Alport syndrome includes a pathogenic <i>COL4A5</i> variant, the consequences depend on the sex of the affected individual, <i>COL4A5</i> variant "severity," and the nature of the <i>COL4A3</i> or <i>COL4A4</i> change. A man with a pathogenic <i>COL4A5</i> variant has all his collagen IV <i>α</i>3<i>α</i>4<i>α</i>5-heterotrimers affected, and an additional <i>COL4A3</i> or <i>COL4A4</i> variant may not worsen disease. A woman with a pathogenic <i>COL4A5</i> variant has on average 50% of her heterotrimers affected, which is increased to 75% with a further <i>COL4A3</i> or <i>COL4A4</i> variant and associated with a higher risk of proteinuria. In digenic Alport syndrome with pathogenic <i>COL4A3</i> and <i>COL4A4</i> variants, 75% of the heterotrimers are affected. The <i>COL4A3</i> and <i>COL4A4</i> genes occur head-to-head on chromosome 2, and inheritance is autosomal dominant when both variants affect the same chromosome (<i>in cis</i>) or recessive when they affect different chromosomes (<i>in trans</i>). This form of digenic disease results in increased proteinuria and a median age of kidney failure intermediate between autosomal dominant and autosomal recessive Alport syndrome. Previous guidelines have suggested that all pathogenic or likely pathogenic digenic variants should be identified and reported. Affected family members should be identified, treated, and discouraged from kidney donation. Inheritance within a family is easier to predict if the two variants are considered independently and if <i>COL4A3</i> and <i>COL4A4</i> variants are known to be inherited on the same or different chromosomes.
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Keywords:
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Alport syndrome; COL4A3; COL4A4; COL4A5 genes; collagen; digenic Alport syndrome; genetic renal disease; kidney failure; proteinuria.
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<p> Figure 1. </p>
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<div class="figure-caption-contents"><b> Digenic <i> COL4A5 </i> plus <i> COL4A3 </i> or… </b></div>
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</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
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<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><b> Digenic <i> COL4A5 </i> plus <i> COL4A3 </i> or <i> COL4A4 </i> variants in males are not associated with… </b></div>
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Figure 1.
</strong>
<div class="figure-caption-contents"><b>Digenic <i>COL4A5</i> plus <i>COL4A3</i> or <i>COL4A4</i> variants in males are not associated with greater disease severity and earlier-onset kidney failure (<i>P</i>=0.75).</b> (A) Effect of digenic <i>COL4A5</i> plus <i>COL4A3</i>/<i>COL4A4</i> variants on heterotrimer formation in men (16). (B) Kidney survival in men with a <i>COL4A5</i> variant (from LOVD) compared with a <i>COL4A5</i> plus a <i>COL4A3</i> or <i>COL4A4</i> variant. The data and references for the digenic variants are summarized in Table 1, and full data are provided in <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.03120322/-/DCSupplemental">Supplemental Table 1</ext-link>. The <i>COL4A5</i> variant (solid line) and the <i>COL4A5</i> plus a <i>COL4A3</i> or <i>COL4A4</i> variant (dashed line) are shown. LOVD, Leiden Open Variation Database.</div>
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<div class="figure-caption-contents"><b> Digenic <i> COL4A5 </i> plus <i> COL4A3 </i> or… </b></div>
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<p> Figure 2. </p>
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<div class="figure-caption-contents"><b> Digenic <i> COL4A5 </i> plus <i> COL4A3 </i> or <i> COL4A4 </i> variants in females are associated with a… </b></div>
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Figure 2.
</strong>
<div class="figure-caption-contents"><b>Digenic <i>COL4A5</i> plus <i>COL4A3</i> or <i>COL4A4</i> variants in females are associated with a trend to earlier onset of proteinuria (<i>P</i>=0.09).</b> (A) Effect of digenic <i>COL4A5</i> plus <i>COL4A3</i>/<i>COL4A4</i> variants on heterotrimer formation in women (16). (B) Proteinuria in women with a <i>COL4A5</i> variant (37) compared with a <i>COL4A5</i> plus a <i>COL4A3</i> or <i>COL4A4</i> variant (Table 2). The data and references for the digenic variants are summarized in Table 2, and full data are provided in <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.03120322/-/DCSupplemental">Supplemental Table 2</ext-link>. The <i>COL4A5</i> variant (solid line) and the <i>COL4A5</i> plus a <i>COL4A3</i> or <i>COL4A4</i> variant (dashed line) are shown.</div>
</figcaption>
</figure>
<figure class="figure-item "
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<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/9718039/707b99054692/CJN.03120322f3.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="3701"
data-image-height="2971"
data-image-alt="Figure 3."
data-pmc-id="PMC9718039"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/9718039/54372238814a/CJN.03120322f3.gif"
alt="Figure 3." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="3701">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="2971">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 3. </p>
</strong>
<div class="figure-caption-contents"><b> Digenic <i> COL4A3 </i> plus <i> COL4A4 </i> variants… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3. </p>
</strong>
<div class="figure-caption-contents"><b> Digenic <i> COL4A3 </i> plus <i> COL4A4 </i> variants are associated with disease severity intermediate between autosomal… </b></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">
Figure 3.
</strong>
<div class="figure-caption-contents"><b>Digenic <i>COL4A3</i> plus <i>COL4A4</i> variants are associated with disease severity intermediate between autosomal dominant and autosomal recessive Alport syndrome (<i>P</i>=0.01, <i>P</i>&lt;0.001, respectively).</b> (A) Effect of digenic <i>COL4A3</i> plus <i>COL4A4</i> variants on heterotrimer formation (16). (B) Kidney survival in digenic Alport syndrome where pathogenic variants affect <i>COL4A3</i> and <i>COL4A4</i> compared with autosomal recessive (43) or autosomal dominant (9) Alport syndrome. The data and references for the digenic variants are summarized in Table 3, and full data are provided in <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.03120322/-/DCSupplemental">Supplemental Table 3</ext-link>. Heterozygous variants (solid line), digenic variants (dotted line), and autosomal recessive variants (dashed line) are shown.</div>
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<h2 class="title">
Publication types
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<div id="mesh-terms" class="mesh-terms keywords-section">
<h2 class="title">
MeSH terms
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Autoantigens / genetics
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Collagen Type IV / genetics
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Pedigree
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ref="linksrc=search_in_pubmed_keyword_link&amp;mesh=&quot;Proteinuria&quot;[MeSH]"
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<div id="substances" class="substances keywords-section">
<h2 class="title">
Substances
</h2>
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Autoantigens
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href="/?term=%22Autoantigens%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc"
data-href="/?term=%22Autoantigens%22%5Bnm%5D&amp;sort=date&amp;sort_order=desc"
ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Autoantigens&quot;[nm]"
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data-ga-label="Autoantigens">
Search in MeSH
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ref="linksrc=add_to_search_link"
role="button"
data-search-term="&quot;Autoantigens&quot;[nm]"
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data-ga-label="&quot;Autoantigens&quot;[nm]"
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Collagen Type IV
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ref="linksrc=search_in_pubmed_keyword_link&amp;keyword=&quot;Collagen Type IV&quot;[nm]"
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<div id="related-links" class="related-links">
<h2 class="title">
Related information
</h2>
<ul class="related-links-list"><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&amp;from_uid=35675912"
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