COMPLETE PENETRANCE OF CREUTZFELDT-JAKOB-DISEASE IN LIBYAN JEWS CARRYING THE E200K MUTATION IN THE PRION PROTEIN GENE

Background: Creutzfeldt-Jakob disease (CJD) is a prion disease which i s manifest as a sporadic, inherited, and transmissible neurodegenerati ve disorder. The mean age at onset of CJD is similar to 60 years, and as such, many people destined to succumb undoubtedly die of other illn esses first. The delayed onset of CJD has complicated the analysis of inherited forms of the illness and led to the suggestion that mutation s in the prion protein (PrP) gene are necessary but not sufficient for prion disease despite genetic linkage; indeed, an environmental facto r such as a ubiquitous virus has been proposed as a second necessary f actor. Materials and Methods: To examine what appeared to be incomplet e penetrance, we applied a life-table analysis to clinical and pedigre e data from a cluster population of Libyan Jews in which the E200K mut ation is prevalent. The study population included 42 affected and 44 u naffected members of 13 Libyan Jewish families, all of whom possessed the E200K mutation. Results: The calculated value using life table ana lysis is 0.77 at age 70 which increases to 0.89 if a mutation carrier survives to age 80 and 0.96 if age 80 is surpassed. Conclusions: These data argue that the E200K mutation alone is sufficient to cause prion disease and does so in an age-dependent manner.