Abstract

Hereditary prion disease is a fatal genetic disorder of autosomal dominant inheritance. Recent phenotype–genotype correlation studies revealed a considerable clinical and pathological overlap for patients with the D178N mutation, suggesting a continous spectrum between fatal familial insomnia and Creutzfeldt–Jakob Disease phenotype. This report adds further evidence to this thesis from a large German prion pedigree with D178N mutation in the PRNP-gene. This pedigree shows an extensive variability in (1) age of disease onset, ranging from 19 to 72 years and including an asymptomatic 73-year-old gene carrier and (2) disease phenotype, including a Gerstmann–Straussler–Scheinker phenotype. These findings have substantial importance for genetic counselling of persons at risk.