Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I

In a family with autopsy-confirmed Alzheimer disease, the authors found a m utation in the presenilin 2 (PS2) gene (PSEN2) that predicts a methionine-t o-isoleucine change at PS2 residue 239 (M239I), at which a change to valine was known in another family. Phenotypic expression of M239I was highly var iable, with disease onset between age 44 and 58 years, and two nonaffected mutation carriers at age 58 and 68 years. The data showed no influence of A POE but were compatible with other possible genetic modifiers of the phenot ype or penetrance of M239I.