title: Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family.
abstract: 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.
authors.affiliation: Division of Neuropathology, Case Western Reserve University, Cleveland, OH.
authors.forename: S
authors.initials: S
authors.lastname: Capellari
authors.forename: C
authors.initials: C
authors.lastname: Vital
authors.forename: P
authors.initials: P
authors.lastname: Parchi
authors.forename: R B
authors.initials: RB
authors.lastname: Petersen
authors.forename: X
authors.initials: X
authors.lastname: Ferrer
authors.forename: D
authors.initials: D
authors.lastname: Jarnier
authors.forename: E
authors.initials: E
authors.lastname: Pegoraro
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
authors.forename: J
authors.initials: J
authors.lastname: Julien
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002531:Cerebellum / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology; D011328:Prions / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013030:Spain
chemical_list: D011328:Prions