MUTATION IN CODON-200 AND POLYMORPHISM IN CODON-129 OF THE PRION PROTEIN GENE IN LIBYAN JEWS WITH CREUTZFELDT-JAKOB-DISEASE

Various mutations in the prion protein (PrP) gene are associated with Creutzfeldt-Jakob disease (CJD), a transmissible fatal neurodegenerati ve disorder. Among Libyan Jews, CJD is a familial disease with an inci dence about 100 times higher than the worldwide population. CJD in thi s community segregates with a point mutation at codon 200 of the PrP g ene which causes the substitution of lysine for glutamate. This mutati on was found in all definitely affected individuals and yields a maxim um lod score of 4.85. Some healthy elderly mutation carriers above 65 years of age were identified, suggesting partial penetrance. Homozygou s patients have the same disease pattern and age of onset as heterozyg ous patients, which argues that CJD associated with the codon 200 lysi ne mutation is a true dominant disorder. In the caucasian population, Palmer et al. (1991) reported an association between homozygosity in a polymorphic site at codon 129 of the PrP gene, coding for either vali ne or methionine, with a tendency to acquire the sporadic or iatrogeni c forms of CJD, as well as with disease age of appearance in the genet ic type. The incidence of the polymorphism at codon 129 in the control Libyan population is similar to the one found in the caucasian popula tion. In the Libyan CJD patients, the codon 200 mutation is within a M et(129)-encoding allele. The incidence of the Met allele is significan tly higher in the affected pedigrees than in the control Libyan popula tion; however, no difference was detected between CJD patients, codon 200 healthy carriers, and their normal family members. Homozygosity at codon 129 did not correlate with age of onset or the clinical course in the Libyan Jewish patients. Our finding suggests that the codon 200 mutation causing CJD in Libyan Jews occurred in an isolated pedigree, and has not propagated since to the general Libyan Jewish community.