NR ACES
AU Capellari,S.; Vital,C.; Parchi,P.; Petersen,R.B.; Ferrer,X.; Jarnier,D.; Pegoraro,E.; Gambetti,P.; Julien,J.
TI Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family
QU Neurology 1997 Jul; 49(1): 133-41
PT journal article
AB 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.
IN Bei einer baskischen Familie bewirkt eine 144 Basenpaar-Insertion in der Oktapeptidregion eine spongiforme Enzephalopathie mit extrem langen Krankheitsphasen von bis zu 10 Jahren und vorwiegend Kleinhirnausfällen. Bei einem Patienten mit einer vierjährigen Symptomphase zeigte die Autopsie nur eine sehr geringe Durchlöcherung an nur einigen Stellen. Hingegen sah man bei einem Patienten nach 10-jähriger Krankheit eine ausgeprägte schwammförmige Degenerierung. Die Mengenverteilunng der Prionproteinamyloide entsprach dem Schädigungsmuster. Im Westernblot unterschieden sich die Bandenmuster des proteinaseresistenten Prionproteine nicht von den sporadischer CJD-Fälle.
ZR 33
MH Adult; Blotting, Western; Cerebellum/pathology; Human; Immunohistochemistry; Male; Pedigree; Polymerase Chain Reaction; Prion Diseases/*genetics/pathology; Prions/*genetics; Repetitive Sequences, Nucleic Acid; Spain; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Division of Neuropathology, Case Western Reserve University, Cleveland, OH.
SP englisch
PO USA