{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:35:20Z","timestamp":1760783720672,"version":"3.40.4"},"reference-count":66,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2013,9,6]],"date-time":"2013-09-06T00:00:00Z","timestamp":1378425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,9,6]],"date-time":"2013-09-06T00:00:00Z","timestamp":1378425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Progranulin (PGRN) mutations are associated with different clinical phenotypes, including frontotemporal lobar degeneration (FTLD), corticobasal syndrome (CBS) and Alzheimer's disease (AD). As all pathogenic &lt;i&gt;PGRN&lt;\/i&gt; mutations identified so far cause disease through haploinsufficiency, determination of PGRN levels has been proposed as a reliable method to identify mutation carriers. &lt;b&gt;&lt;i&gt;Objective:&lt;\/i&gt;&lt;\/b&gt; To evaluate the accuracy of peripheral PGRN levels in the identification of the &lt;i&gt;PGRN&lt;\/i&gt; mutation carriers detected thus far in our Portuguese cohort. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Serum PGRN levels were measured in 244 subjects (124 patients in the spectrum of FTLD, 2 asymptomatic descendants of a FTLD patient, 56 AD patients and 64 controls) by a novel commercial ELISA kit. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Low PGRN levels were detected in 7 individuals (5 behavioral variant frontotemporal dementia, 1 CBS, and 1 still clinically unaffected) that constituted the group of the null &lt;i&gt;PGRN&lt;\/i&gt; mutation carriers previously identified in our molecular diagnostic laboratory. The pathogenic mutations found consisted of 4 insertion-deletions, causing frameshifts resulting in premature stop codons, 3 of which were novel. In addition, a normal PGRN level was found in a patient harboring a novel missense variant. For this novel ELISA kit, we established a PGRN cut-off level that identified with 100% accuracy the pathogenic mutation carriers. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; This study supports the use of a novel assay for the determination of PGRN levels as a screening procedure to identify patients harboring null &lt;i&gt;PGRN&lt;\/i&gt; mutations. This approach would significantly decrease the required &lt;i&gt;PGRN&lt;\/i&gt; mutation analysis workload and should be extended to other clinical phenotypes than behavioral variant frontotemporal dementia and to apparently sporadic cases.<\/jats:p>","DOI":"10.1159\/000352022","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T08:05:25Z","timestamp":1378368325000},"page":"214-223","source":"Crossref","is-referenced-by-count":29,"title":["Progranulin Peripheral Levels as a Screening Tool for the Identification of Subjects with Progranulin Mutations in a Portuguese Cohort"],"prefix":"10.1159","volume":"13","author":[{"given":"Maria Ros\u00e1rio","family":"Almeida","sequence":"first","affiliation":[]},{"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[]},{"given":"Maria 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