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.
Copyright © 2012 S. Karger AG, Basel.