A novel mutation (L250V) in the presenilin 1 gene in a Japanese familial Alzheimer's disease with myoclonus and generalized convulsion.

This study reports a novel presenilin 1 (PS1) gene mutation in a Japanese family with Alzheimer's disease (AD). Two patients developed progressive memory disorder with disorientation around 50 years of age and showed myoclonus with frequent tonic-clonic seizures several years later. Direct sequencing of the proband's PS1 gene revealed a novel mis-sense mutation (leucine-to-valine at residue 250 (L250V)). This mutation was found in both patients, but not in a normal family member or normal Japanese control subjects. Thus, L250V is a novel PS1 gene mutation responsible for familial AD (FAD) in Japan.