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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
Author(s) -
Plaitakis Andreas,
Viskadouraki Anna K.,
Tzagournissakis Minas,
Zaganas Ioannis,
VergheseNikolakaki Susan,
Karagiorgis Vasilis,
Panagiotides Ioannis,
Kilindireas Constantine,
Patsouris Eustratios,
Haberler Christine,
Budka Herbert,
Sklaviadis Theodoros
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1285
Subject(s) - prnp , population , incidence (geometry) , dementia , biology , methionine , medicine , genotype , pathology , genetics , disease , gene , physics , environmental health , amino acid , optics
Abstract Since the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, 9 cases (8 neuropathologically confirmed and 1 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 versus 41.5%, n = 859. 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.