Japanese Creutzfeldt-Jakob disease patients exhibiting high incidence of the E200K PRNP mutation and located in the basin of a river.

Seven cases with Creutzfeldt-Jakob disease (CJD) located in the basin of the Fuji river (Fuji area) in Japan were examined genetically and clinicopathologically. The onset of the disease was between 1989 and 1995. All cases were from different families, although 3 cases were family members of previously reported CJD patients. They had clinical and/or neuropathological features, corresponding to subacute spongiform encephalopathy. Five of the 7 cases, including the 3 familial cases, had the E200K mutation in the gene encoding prion protein (PRNP). It is suggested that there is a small cluster of CJD patients with a founder effect of the E200K mutation in the Fuji area, because the incidence of CJD with the E200K mutation appears to be much higher in this area than other areas in Japan. The disease penetrance of the 5 cases with the E200K mutation seems to be low, and they may have an age-related incidence in the Fuji area. These findings support the hypothesis that the phenotypes of CJD patients with the PRNP mutations are linked to the position of the mutation, but not related to ethnic or environmental factors.