Increased incidence of sporadic Creutzfeldt-Jakob disease on the island ofCrete associated with a high rate of PRNP 129-methionine homozygosity in the local population

Since the spring of 1997, when the Neurology Department of the University H ospital of Crete admitted its first patient, nine cases (eight neuropatholo gically confirmed and one probable) of sporadic Crentzfeldt-Jakob disease ( sCJD) have been recorded. This represents an annual incidence five-fold hig her than expected based on the island's population (0.54 million). Molecula r analysis of the prion-protein gene (PRNP) showed no mutations in any of t he seven CJD cases studied. Five patients (ages 64-88 years) were homozygou s for methionine-129 of PRNP and showed the classic sCJD triad (subacute de mentia, myoclonus, periodic electroencephalogram). Brains contained type 1 (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). T wo patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementia not associated with periodic electroen cephalogram; brain PrPres was type 2. Genotyping of 205 Cretan controls sho wed that methionine-129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian population s (57.0% n = 205 vs. 41.5% n = 859, p < 0.0001). These data are the first t o relate a high regional incidence rate for sCJD to the distribution of PRN P 129 genotypes in the local population; however, additional factors may be operational.