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Vol. 33, No. 2-3, 2012
Issue release date: June 2012
Section title: Original Research Article
Dement Geriatr Cogn Disord 2012;33:132–140
(DOI:10.1159/000338394)

Different Clinical Phenotypes in Siblings with a Presenilin-1 P264L Mutation

Ishizuka T. · Nakamura M. · Ichiba M. · Fujita S. · Takeuchi K. · Fujimoto T. · Sano A.
aDepartment of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, bDepartment of Radiology, Fujimoto Hayasuzu Hospital, and cDepartment of Psychiatry, Fujimoto Hospital, Miyazaki, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 3/28/2012
Published online: 5/8/2012

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM

Abstract

Background: Mutations in the presenilin-1 gene (PSEN1) have been identified in autosomal dominant early-onset cases of Alzheimer’s disease (AD). Aims: To investigate different clinical phenotypes of siblings possessing the same heterozygous P264L mutation in the PSEN1 gene. Methods: We evaluated clinical features, neuroimaging results, and neuropsychological examinations. The PSEN1 gene and other dementia-related gene mutations were screened. Results: 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 PSEN1 gene was identified in both siblings. Conclusion: 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 PSEN1 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.


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 3/28/2012
Published online: 5/8/2012

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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