[01] Mitrova Eva, Slovak Medical University Bratislava, Institute of Microbiology, Department of prion diseases, Bratislava, Slovakia. [02] Belay Girma, Slovak Medical University Bratislava, Institute of Microbiology, Department of prion diseases, Bratislava, Slovakia. [03] Slivarichova – Zakova Dana, Slovak Medical University Bratislava, Institute of Microbiology, Department of prion diseases, Bratislava, Slovakia. [04] Stelzer Martin, Slovak Medical University Bratislava, Institute of Microbiology, Department of prion diseases, Bratislava, Slovakia.

The first case of Creutzfeldt-Jakob disease, methionine / valine heterozygous at codon 129 with a rare mutation at codon 208 (mutation R208H) of the prion protein gene is presented. Comparison to previously described patients with the same mutation R208H, but methionine or valine homozygous at codon 129 was performed. It revealed similarity in the duration of clinical manifestation, in histopatological lesions and in negative family history, Heterozygosity in codon 129 was characterized by similar clinical symptoms as described in 129MM cases, with dominant psychiatric symptomatology also in prodromal phase, by slightly higher age at death and markedly prolonged prodromal stage of the disease.

Creutzfeldt-Jakob Disease, Duration, Mutation R208H, Polymorphism M129V

[01] Alperovitch, A., Zerr, I., Windl, O. et al.: Genetic epidemiology of CJD in Europe. Rev. neurol. (Paris) 2002; 157, 1-7: 633-637. [02] Mitrová E and Belay G.: Creutzfeldt-Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 2002; 46: 31-39. [03] Kovacs,G., Puopulo M., Ladogana A. et al.: Genetic prion disease : the EUROCJD experience. Hum Genet 2005, 118: 166-174. [04] Mastrianni JA, Iannicola RM, Myers S, et al.: Mutation of the PRNP at codon 208 in Familial CJD. Neurology, 1996; 48: 1305. [05] Capellari S, Ladogana A, Volpi G, et al.: First report of the R208H 129MM haplotype in the PRNP in a European subject with CJD. Neurol Sci 2001; 22:109. [06] Capellari S., Cardone F., Notari S. et al.: Creutzfeldt- Jakob disease associated with the R208H mutation of the prion protein gene. Neurology, 2005; 64: 905-907. [07] Roeber S, Krebs B, Neumann M, et al.: CJD in a patient with an R208H mutation of the PRNP and a 17-kDa prion protein fragment. Acta Neuropathol 2005;109: 443-448. [08] Chen C., Shi Q, Tian C. et al.: The first Chinese case of CJD patient with R208H mutation in PRNP. PRION 2011, Juli 1:5 (3):232-4. [09] Basset-Leobon C., Uro-Coste E., Peoc´h K, et al.: Familial CJD with an R208H-129V haplotype and kuru plaques. Arch Neurol 2006; 63: 449-452. [10] Matej R., Kovács GG., Johanidesová S, et al. Genetic CJD with R208H mutation presenting as progressive supranuclear palsy. Clinical Vignettes, 2012; 27 (4): 476-479. [11] Mead,S. Prion disease genetics. Europ. J. Human Genet. 2006; 14: 273-281. [12] Zuegg,J. and Gready,JE.: The role of helix 1 aspartates and salt bridges in the stability and conversion of prion potein. Biochemistry, 1999; 38:13 862-13876 . [13] Bamdad K. and Naderi-Manesh H. Contribution to a putative salt bridge and backbone dynamics in the structural instability of human prion protein upon R208 mutation. Biochem Biophys Res Commun, 2007; 364 (4): 719-724. [14] Cardone F, Principe S., Schininá ME, et al. Mutant PrPCJD prevails over wild-type PrPCJD in the brain of V210I and R208H genetic CJD patients. Bioch.Biophys. Res.Comm. 2014; 826-828. [15] Laplanche,J., Delasnerie-Laupretre,N., Brandel,J. et al.: Molecular genetics of prion diseases in France. Neurology 1994, 44: 2347-2351. [16] Collinge, J. Palmer,M. and Gryden,A.: Genetic predisposition to iatrogenic CJD. Lancet, 1991; 337: 1441-1442. [17] Mitrová E, Mayer,V, Jovankovičová V, et al. CJD risk and PRNP codon 129 polymorphism: necessity to revalue current data. Eur J Neurol 2005; 12: 1-4. [18] Will,R.: New variant of CJD. Biomed Pharmacoth, 1999; 53: 9-13. [19] Nurmi,M.,H., Bishop,M., Strain,L. et al.: The normal population distribution of PRNP codon 129 polymorphism. Acta Neurol Scand, 2003; 108: 374-378. [20] Parchi P, Giese A., Capellari, S, et al.: Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.