In summary, the present results bring to 13 the number of PrP point mutations associated with familial prion disease which have been tested for transmission. Of these, 9 mutations have showed evidence for transmission to primates or rodents. PrP Y226X is the first PrP mutation encoding a truncated PrP molecule which was transmissible. In contrast, the other truncated PrP mutant tested here, Q227X, showed no evidence for transmission which was similar to two other truncation mutants previously tested by others. These differences in transmission might be due to the influence of specific protein folding structural factors on generation of infectivity, or alternatively, they might be due to biological statistical variation in the quantity of prion infectivity present in the brain samples tested.