Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene

The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion p rotein (PrP) gene are described. Genetic analysis of the mutated allele rev ealed a sequence of live extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the documented subjects. Neuropathological evaluation sh owed neuronal loss and gliosis in the neocortex of the 3 examined cases; sp ongiform degeneration was found in 2 of them. PrP immunoreactivity of unusu al morphology and distinct distribution was present in the cerebellum and n eocortex ("blurred staining") of 2 examined cases. One subject showed featu res usually found in sporadic Creutzfeldt-Jakob disease with a punctate typ e of PrP deposition in the cerebellum. In addition, there were some plaque- like PrP aggregates morphologically similar to the other 2 cases in the mol ecular layer of the cerebellum, and unusual PrP immunoreactivity ("fleecy s taining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.