Objective: To describe a novel mutation (K239N) in the PSEN1 associated with familial Alzheimer's disease (AD).
Methods and results: The proband was a man who developed cognitive decline with marked behavioural abnormalities at age 57. At age 70, he was admitted into a psychiatric facility because of aggressiveness and a suicide attempt. Family history was consistent with autosomal dominant AD. One of the two other family members studied presented also with prominent behavioural symptoms at age 42 and has also been forced into a psychiatric facility because of aggressiveness at age 56. The remainder patient has presented a prototypical AD, but starting at age 71. Direct sequencing of PSEN1 in the three living affected members disclosed a heterozygous G to C transition in exon 7 of PSEN1 leading to the K239N mutation.
Conclusion: The K239N mutation is associated with autosomal dominant AD with a wide range of age of onset and incomplete penetrance at the age of 65, prominent behavioural features and slow progression.