Rare E196K mutation in the PRNP gene of a patient exhibiting behavioral abnormalities

Abstract 

Genetic transmissible spongiform encephalopathies (TSEs) account for approximately 10–15% of overall human prion diseases worldwide, but genotype–phenotype correlations remain incomplete. Here we report the case of an 80-year-old man who developed rapidly progressive behavioral abnormalities and myoclonus following a stroke. Repeated electroencephalography (EEG) revealed a general slowing of the basic activity, as well as several episodes of triphasic waves, with neither periodic activity nor recorded seizure. 14.3.3 protein was detected in cerebral cerebrospinal fluid, and direct sequencing of the PRNP gene showed an E196K mutation associated with homozygosity for methionine at codon 129. The patient was diagnosed with probable genetic prion disease with a Creutzfeldt-Jakob disease-like phenotype. The PRNP E196K mutation has only rarely been described in the literature, and generally patients exhibited an atypical initial phenotype, mainly involving abnormal behavioral features. Further observations are needed to confirm this particular clinical pattern associated with the mutation.

Keywords: Creutzfeldt-Jakob disease, Transmissible spongiform encephalopathies, Genetic, Prion protein gene, PRNP, Point mutation