{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:57:35Z","timestamp":1784383055610,"version":"3.55.0"},"reference-count":43,"publisher":"S. Karger AG","issue":"2-3","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dement Geriatr Cogn Disord"],"published-print":{"date-parts":[[2012]]},"abstract":"<b><i>Background:<\/i><\/b> Mutations in the presenilin-1 gene <i>(PSEN1)<\/i> have been identified in autosomal dominant early-onset cases of Alzheimer\u2019s disease (AD). <b><i>Aims:<\/i><\/b> To investigate different clinical phenotypes of siblings possessing the same heterozygous P264L mutation in the <i>PSEN1<\/i> gene. <b><i>Methods:<\/i><\/b> We evaluated clinical features, neuroimaging results, and neuropsychological examinations. The <i>PSEN1<\/i> gene and other dementia-related gene mutations were screened. <b><i>Results:<\/i><\/b> We clinically diagnosed the proband as atypical AD with frontotemporal dementia features and diagnosed the elder brother of the proband as typical AD, based on neuropsychological symptoms and a brain imaging examination including amyloid imaging data. A heterozygous P264L mutation in the <i>PSEN1<\/i> gene was identified in both siblings. <b><i>Conclusion:<\/i><\/b> This study is one of few reports of AD siblings possessing the same mutation but exhibiting different clinical phenotypes in a Japanese family possessing a P264L mutation in the <i>PSEN1<\/i> gene. The current results suggest that unknown modifiers, including both genetic and epigenetic factors, may alter the pathological and clinical phenotypes of a genetically predetermined disease.<\/jats:p>","DOI":"10.1159\/000338394","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T09:51:15Z","timestamp":1336470675000},"page":"132-140","source":"Crossref","is-referenced-by-count":6,"title":["Different Clinical Phenotypes in Siblings with a Presenilin-1 P264L 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