PRNP and Creutzfeldt Jacob disease: The hypothesis posits that the first prion in a patient with sporadic CJD originated in a cell or group of cells which acquired a somatic mutation in PRNP. A strong candidate for this original mutation is the somatic insertion of additional repeats in the OPR, as OPRIs can cause inherited CJD and somatic instability is commonly seen for repetitive sequences43.