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Vol. 33, No. 2-3, 2012
Issue release date: June 2012
Dement Geriatr Cogn Disord 2012;33:132–140

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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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.

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