Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family

• Published in: Neurology Vol. 49; no. 1; p. 133
• Main Authors: Capellari, S, Vital, C, Parchi, P, Petersen, R B, Ferrer, X, Jarnier, D, Pegoraro, E, Gambetti, P, Julien, J
• Format: Journal Article
• Language: English
• Published: United States 01.07.1997
• Subjects: Adult; Blotting, Western; Cerebellum - pathology; Humans; Immunohistochemistry; Male; Pedigree; Polymerase Chain Reaction; Prion Diseases - genetics; Prion Diseases - pathology; Prions - genetics; Repetitive Sequences, Nucleic Acid; Spain; Spain
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.49.1.133

Three members of a Basque family carrying a novel six R2 octapeptide repeat 144-bp insertion in the prion protein gene (PRNP) showed a slowly progressive dementia associated with cerebellar signs, myoclonic jerks, and seizures. Although postmortem examination revealed only focal and minimal spongiform degeneration in one subject with a 4-year course, significant astrogliosis and neuronal loss were associated with pronounced spongiform degeneration in the patient with a duration of symptoms of 10 years. Prion protein (PrP)-immunoreactive patches with a unique morphology were present in the molecular layer of the cerebellum in both subjects. Western blot analysis demonstrated the presence of protease-resistant prion protein (PrPres) with the same characteristics (size and ratio of the three differently glycosylated isoforms) of that found in typical sporadic Creutzfeldt-Jakob disease (CJD129M/M, PrPres type 1). The amount of PrPres correlated with presence and severity of spongiform degeneration in the cerebral cortex. The findings suggest that a relatively low rate of PrPres deposition is the cause of the lack of spongiform degeneration in subjects carrying a 144-bp insertion in PRNP. The presence of PrP-immunoreactive patches with unique morphology in the molecular layer of the cerebellum is a hallmark of certain prion encephalopathies with insertional mutations and is useful in the diagnosis of this subtype of human prion disease.