Creutzfeldt-Jakob disease (CJD), the most important human
prion disease, occurs in sporadic, iatrogenic and familial form. Except Slovakia and Israel, the recorded familial cases have never exceeded 10-15%. In the Slovak CJD group 95 out of 136 CJD cases (74.2%) carried a CJD-specific mutation in the
prion protein gene (PRNP) at
codon 200 (mutation E200K). All CJD(E200K) patients carried a heterozygous E200K mutation within the alelle with
methionine at
codon 129. No more than 53.7% were typical familial cases. The penetrance of the E200K mutation in 1975-2000 was 59.5%. The distribution of
codon 129 polymorphism showed 78.6% of
methionine-homozygous and 21.4% of
methionine/
valine-heterozygous patients. Genetic analysis performed on 278 CJD patient relatives demonstrated the E200K mutation in 97 (34.8%) of healthy relatives tested. The E200K mutation carriers were
methionine-homozygous in 64% and
methionine/
valine-heterozygous in 36%. The relatives without the mutation showed a 54.9%
methionine homozygosity, 10.4%
valine homozygosity and 34.7%
methionine/
valine heterozygosity. Analysis ofthe E200K carriers provided evidence that the
methionine homozygosity is a CJD risk factor, more efficient in CJD patients than in asymptomatic relatives. Th influence of both the E200K mutation and
methionine homozygosity at
codon 129 was evident in the duration of the clinical stage of CJD and in the immunoreactivity pattern of PrP resistant to
proteases (
PrP(res)). In the CJD(E200K)
methionine-homozygous patients the mean duration ofthe disease was significantly shorter (3.7 +/- 2.0 months) than in the
methionine/
valine-heterozygous patients (7.84 +/- 7.3 months). Comparison of the
PrP(res) positivity in the cerebellum of familial and
sporadic CJD using specific polyclonal and
monoclonal antibodies (MAbs) to PrP showed less conspicuous immune reaction in CJD(E200K) cases.
Methionine-homozygous CJD patients were characteristic mainly by synaptic pattern of staining, while
methionine/
valine-heterozygous patients by
PrP(res) granules and plaque-like structures. Most of numerous plaque-like
PrP(res) deposits were found in sporadic
valine/
valine-homozygous cases. Potential professional risk was excluded in health facility workers. The percentage of professions related to farming was significantly higher in CJD(E200K) (48%) and
sporadic CJD (44%) cases as compared to the employed population (9%).