Penetrance of the V203I variant of the PRNP gene: report of a patient with stroke-like onset of Creutzfeld-Jacob Disease and review of published cases.

Creutzfeldt-Jakob disease (CJD) is usually sporadic, but 10-15% of cases are caused by autosomal-dominant pathogenic variants in the prion protein gene (). A few variants show low penetrance. We report the case of a 64-year-old man, admitted to the ward with acute onset of aphasia; death occurred 6 weeks later. Brain MRI, EEG pattern and brain pathology were consistent with CJD diagnosis. Genetic analysis revealed a heterozygous V203I variant. We summarized the key clinical findings in patients carrying the V203I variant who were described to date. We also discuss the hypothesis as to whether V203I is a risk factor for CJD rather than a Mendelian disease-associated variant, as well as the possible implications of such hypothesis in the clinical scenario.