Fatal familial insomnia, associated with PRNP mutation (clinical case)

Background. Prion diseases or transmissible spongiform encephalopathies are a group of neurodegenerative disorders characterized by rapidly progressive dementia and movement disorders. Prion diseases can be acquired, sporadic, genetic (inherited), and are characterized by the accumulation and aggregation of prions or abnormally coiled proteins. The diseases have a long incubation period (years) but progress rapidly after the manifestation of clinical symptoms. The most common human prion diseases are sporadic in nature. Prion diseases include sporadic Creutzfeldt – Jakob disease, as well as rare cases of sporadic fatal insomnia and variable protease-sensitive prionopathy. The diseases have a long incubation period (years), but progress rapidly after the manifestation of clinical symptoms. Fatal familial insomnia (Insomnia, fatal familial; OMIM: # 600072) is a rare autosomal dominant neurodegenerative disease with high penetrance and associated with mutation in PRNP gene.Results. The article presents clinical case of 15-year-old patient with severe mental development disorder, motor excitability, hyperactivity of sympathetic nervous system and insomnia. The previously described variant in PRNP gene (D178N) was detected by whole exome sequencing. Validation of the mutation in the proband and segregation analysis were carried out: mutation c.532G>A, Asp178Asn in PRNP gene was identified in the proband and his 50-year-old father, who had no signs of prion disease. at the time of the study. Additionally, adenine in the 358th position was found in a homozygous state, which is responsible for the frequent M129M polymorphism in Sanger sequencing of PRNP gene in the proband and his father.Conclusion. The description of the clinical case of fatal familial insomnia in Russia presented by the authors clearly shows the likely difficulties that doctors may face when examining such patients. The diagnosis (clinical, genetic using massively parallel sequencing methods) remains important in relation to medical genetic counseling and family planning, since methods of pathogenetic therapy for hereditary prion diseases have not currently been developed.