Prion protein gene M232R variation is probably an uncommon polymorphism rather than a pathogenic mutation

Sir, Nozaki et al. (2010) present a 10-year surveillance study in Japan with important implications for inherited prion disease diagnosis and counselling of families. The most frequent mutations reported were V180I and M232R , however, we are concerned about the conclusion that M232R is pathogenic. It is important to correctly understand the pathogenicity of variants to inform counselling of those at risk in families and to take precautionary public health measures to prevent transmission of iatrogenic prion disease from gene carriers. Additionally, the pathogenicity of M232R would be surprising from the perspective of the pathobiology of prion disease because this amino acid is cleaved from the mature cell surface prion protein in the …