MOLECULAR-GENETICS OF PRION DISEASES IN FRANCE

Human prion diseases are characterized by the accumulation in the brai n of an abnormal form of the prion protein. Prion protein polymorphism s seem to play a key role in the pathogenesis of these diseases, proba bly by enhancing the amyloidogenic properties of the protein. We perfo rmed prion protein gene (PRNP) coding sequence analysis in 57 French s ubjects with Creutzfeldt-Jakob disease (CJD) and found a mutation of t he PRNP coding sequence in nine subjects (15.8%); the mutation corresp onded with a known family history of CJD in only three of these subjec ts. In 41 definite and probable cases without known PRNP mutations, co don 129 genotyping revealed an excess of the homozygous 129Met/Met gen otype corresponding to a 3.4-fold increased risk of developing CJD whe n compared with the two other genotypes. We also found that the 129Val /Val genotype, which mainly governs susceptibility to iatrogenic CJD, does not seem to predispose to sporadic CJD.