A MUTATION IN ALZHEIMERS-DISEASE DESTROYING A SPLICE ACCEPTOR SITE INTHE PRESENILIN-1 GENE

A series of mutations has been reported in the presenilin-1 (PS-1) gen e which cause early onset Alzheimer's disease (AD). The mutations repo rted to date have encoded missense mutations which alter residues cons erved between PS-1 and the presenilin-2 (PS-2) gene. We have recently determined the intron/exon structure of the PS-1 gene and this informa tion has been used to identify a mutation in the splice acceptor site for exon 9 in a family with early onset AD. Amplification of cDNA from lymphoblasts of affected individuals revealed that the effect of the mutation was to cause splicing out of exon 9, however it does not chan ge the open reading frame of the mRNA. The importance of this observat ion is discussed.