Two-octapeptide repeat deletion of prion protein associated with rapidly progressive dementia

Insertions of integral numbers of an octapeptide repeat in the prion protei n gene are pathogenic mutations associated with inherited prion diseases. C onversely, deletions of a single octapeptide repeat are found as normal pol ymorphisms in many populations and do not predispose individuals to prion d isease. The authors report a two-octapeptide repeat deletion in an elderly woman with a rapidly progressive dementia consistent with Creutzfeldt-Jakob disease. This mutation was absent from more than 3,000 individuals and may be causally related to prion disease and represent a novel disease mechani sm.