Creutzfeldt Jakob Disease Associated with the R208H-129V Haplotype in the Protein Gene

Human Transmissible Spongiform Encephalopaties (TSEs) or prion diseases occur in sporadic, acquired and genetic forms. All the genetic forms of human TSEs are linked to point or insertion mutations of the PRNP and several of these genetic forms are transmissible. Among the rarer point mutations, R208H was reported in 3 patient (JA. Mastrianni; et al. 1996; S. Capellari et al. 2005; C. Basset-Leobon et al. 2006). Here we described the clinical and pathological features of the CJD phenotype associated with the R208H-129VV haplotype in an Italian patient. Case report A 64-year-old woman was referred to the Italian National Register of the Creutzfeldt-Jakob disease and related disorders, with a clinical presentation characterized by mood disorder and ataxia. Two months after the onset, she showed cognitive decay, cerebellar symptoms, pyramidal symptoms involving the left leg, and a progressive action myoclonus of left hand. Four months later the patient was bed ridden in a state of akinetic mutism. The family history was negative for dementia or neurological disorders. The protein 14-3-3 test gave a positive result. The EEG became typical 4 months after the onset. The MRI of the brain showed mild hyperintense signals in the basal ganglia on T2-weighted images. The sequence of the PRNP gene ORF revealed a mutation at the codon 208 with the substitution of histidine for arginine (R208H) and the polymorphism Val/Val at the level of the codon 129. Death occurred 28 months after onset. Neuropathological examination showed severe spongiform changes in the cerebral cortex, striatum, thalamus and cerebellum. Conclusions: this report is the first on the R208H mutation found in association with val/val polymorphism in Italy and it strengthens the linkage of the R208H mutation to CJD.