Hereditary form of prion disease in Poland.

Abstract Background and purpose The aim of the study was to perform molecular analysis in a group of patients affected with prion disease. Diagnosis was based on results of clinical and/or histopathological examination of the brain. This is the largest investigation of this type performed so far in Poland. Material and methods Analysed material contained 36 cases of prion disease, including 35 cases of Creutzfeldt-Jakob disease and one case of Gerstmann-Straussler-Scheinker disease, as well as two familial cases initially suspected of Huntington disease and Alzheimer disease. The control group consisted of 87 subjects. The most frequent known mutations in the PRNP gene were looked for, namely those in codons 102, 117, 178, 200, 217 and OPRI; the polymorphism Met/Val in codon 129 was also analysed. The methods applied were PCR-RFLP and DNA sequencing. Results The following mutations were found: E200K in 5 families, P102L in one family (previously identified), D178N in one family and 6OPRI in one family. Overall, mutations were detected in 17 persons (including 8 preclinical ones) from 8 pedigrees. Highly significant difference of codon 129 Met/Val heterozygosity frequencies was found between the affected subjects and the controls. Frequency of the familial form of prion disease in the material analysed was 14%. Conclusions Screening for mutations in the PRNP gene should be performed in all diagnosed cases of prion disease and cases of familial occurrence of early onset dementia of unknown aetiology. Families with identified mutations should be offered genetic counselling and informed of risks of blood and organs’ donation.