title: Increased incidence of sporadic Creutzfeldt-Jakob disease on the island of Crete associated with a high rate of PRNP 129-methionine homozygosity in the local population.
abstract: Since the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, nine cases (eight neuropathologically confirmed and one probable) of sporadic Creutzfeldt-Jakob disease (sCJD) have been recorded. This represents an annual incidence five-fold higher than expected based on the island's population (0.54 million). Molecular analysis of the prion-protein gene (PRNP) showed no mutations in any of the seven CJD cases studied. Five patients (ages 64-88 years) were homozygous for methionine-129 of PRNP and showed the classic sCJD triad (subacute dementia, myoclonus, periodic electroencephalogram). Brains contained type 1 (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). Two patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementia not associated with periodic electroencephalogram; brain PrPres was type 2. Genotyping of 205 Cretan controls showed that methionine-129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian populations (57.0% n = 205 vs. 41.5% n = 859, p < 0.0001). These data are the first to relate a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes in the local population; however, additional factors may be operational.
authors.affiliation: Department of Neurology, University of Crete, School of Health Sciences, Heraklion, Greece. plaitakis@med.uoc.gr
authors.forename: A
authors.initials: A
authors.lastname: Plaitakis
authors.forename: A K
authors.initials: AK
authors.lastname: Viskadouraki
authors.forename: M
authors.initials: M
authors.lastname: Tzagournissakis
authors.forename: I
authors.initials: I
authors.lastname: Zaganas
authors.forename: S
authors.initials: S
authors.lastname: Verghese-Nikolakaki
authors.forename: V
authors.initials: V
authors.lastname: Karagiorgis
authors.forename: I
authors.initials: I
authors.lastname: Panagiotides
authors.forename: C
authors.initials: C
authors.lastname: Kilindireas
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
authors.forename: C
authors.initials: C
authors.lastname: Haberler
authors.forename: H
authors.initials: H
authors.lastname: Budka
authors.forename: T
authors.initials: T
authors.lastname: Sklaviadis
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000235:genetics*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D005260:Female; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors