POLYMORPHISMS OF THE PRION PROTEIN GENE IN ITALIAN PATIENTS WITH CREUTZFELDT-JAKOB-DISEASE

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative d isorder characterized by the accumulation of the amyloid protein PrP i n the CNS. TWO coding polymorphisms of the PrP gene (PRNP) are a methi onine (Met) to valine (Val) change at codon 129, and a deletion in the octapeptide coding region. In the United Kingdom, homozygosity at cod on 129 appears to be associated with a predisposition to develop CJD. However, in Japan, where allelic frequencies and genotype distribution are significantly different, such an association has not been demonst rated. To determine whether such deletion(s) or codon 129 polymorphism s of PRNP predispose to the development of CJD in Italian patients, 31 sporadic CJD patients with no known PRNP mutations, and 186 unrelated control subjects were studied. Genotypic frequencies at codon 129 in these Italian CJD patients revealed a significant excess of methionine alleles, and a different genotype distribution in comparison with the normal Italian population. Deletions of a 24-bp segment located in th e PrP octapeptide coding region evert found in two control subjects, b ut in none of the sporadic CJD patients. These data suggest that Met h omozygosity at codon 129 may contribute, with other enviromental or en dogenous factors, to CJD development.