Penetrance and phenotypic expression of a mutation linked to Creutzfeldt-Jacob disease in the elderly

We have previously reported several carriers of the PRNP E200K point mutation among subjects aged over 65 years. In order to examine the prevalence of this mutation among demented subjects of Libyan and Tunisian origin and the clinical characteristics associated with it, we screened 58 elderly subjects belonging to this ethnic group. Five mutation carriers were identified, all of whom had cognitive deterioration consistent with primary degenerative dementia. All had low Hachinski ischemic scores (0.8 ± 0.8, mean ± SD) as compared with noncarriers (6.7 ± 3.0; p = 0.011, Wilcoxon rank sum test). In addition to the cognitive decline, 4 carriers had additional cerebellar, pyramidal, or extrapyramidal findings compatible with the diagnosis of possible or probable Creutzfeldt-Jakob disease.