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

S. Capellari, C. Vital, P. Parchi, R. B. Petersen, X. Ferrer, D. Jarnier, E. Pegoraro, P. Gambetti, J. Julien

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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 (PrP(res)) with the same characteristics (size and ratio of the three differently glycosylated isoforms) of that found in typical sporadic Creutzfeldt-Jakob disease (CJD129M/M, PrP(res) type 1). The amount of PrP(res) correlated with presence and severity of spongiform degeneration in the cerebral cortex. The findings suggest that a relatively low rate of PrP(res) 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.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalNeurology
Volume49
Issue number1
Publication statusPublished - Jul 1997

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Capellari, S., Vital, C., Parchi, P., Petersen, R. B., Ferrer, X., Jarnier, D., Pegoraro, E., Gambetti, P., & Julien, J. (1997). Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family. Neurology, 49(1), 133-141.