A novel presenilin 2 gene mutation (D439A) in a patient with early-onset Alzheimer's disease

The authors describe a novel missense mutation in the presenilin 2 (PSEN2) gene at residue 439 that predicts an aspartate-to-alanine substitution (D43 9A). This mutation was found in a 58-year old patient who displayed a progr essive dementia at the age of 52. The mutation was absent in his cognitivel y normal relatives. Haplotype analysis indicated that his affected mother w as the most probable mutation carrier. The D439A mutation is located near t he C-terminal end of the PS2 protein, a region critical for endoproteolytic processing.