NR AJKG
AU Petersen,R.B.; Tabaton,M.; Chen,S.G.; Monari,L.; Richardson,S.L.; Lynch,T.; Manetto,V.; Lanska,D.J.; Markesbery,W.R.; Currier,R.D.; Autilio-Gambetti,L.; Wilhelmsen,K.C.; Gambetti,P.
TI Familial progressive subcortical gliosis: presence of prions and linkage to chromosome 17.
QU Neurology 1995 Jun; 45(6): 1062-7
ER Neurology 1995 Jul;45(7):1430
PT journal article
AB Progressive subcortical gliosis (PSG) is a sporadic and familial dementing disease characterized pathologically by astrogliosis at the cortex-white matter junction, a feature present in some prion diseases. With immunocytochemical and Western blot analyses, we investigated the presence of deposits of the prion protein (PrP) and of the protease-resistant PrP isoform, the hallmarks of prion diseases, in six affected members of two large kindreds with PSG. The coding region of the PrP gene was sequenced and chromosomal linkage determined. We demonstrated "diffuse" PrP plaques in the cerebral cortex of two subjects from one kindred and protease-resistant PrP fragments in four of the five subjects examined. We found no mutation in the coding region of the PrP gene. Moreover, the disease was linked to chromosome 17 and not to chromosome 20, where the PrP gene resides. The familial form of PSG is the first human genetic disease characterized by the presence of protease-resistant PrP that lacks a mutation in the coding region of the PrP gene. The linkage to chromosome 17 suggests that other genes are involved in the PrP metabolism. Whether the protease-resistant PrP plays a primary or secondary role in the pathogenesis of this form of PSG remains to be determined.
IN Auch bei PatientInnen mit der erblichen, progressiven subkortikalen Gliose wurden kleine Ansammlungen proteaseresistenter Prionproteine gefunden. In den kodierenden Regionen der Prionproteingene entsprechender PatientInnen wurde keine Mutation gefunden und die Krankheit soll mit dem Chromosom 17 und damit unabhängig vom Prionproteingen auf Chromosom 20 vererbt werden.
ZR 55
MH Adult; Brain Diseases/drug therapy/*genetics/metabolism; *Chromosomes, Human, Pair 17; Endopeptidase K; Female; Gliosis/drug therapy/*genetics/metabolism; Human; *Linkage (Genetics); Male; Middle Age; Prions/*analysis/genetics; Serine Endopeptidases/therapeutic use; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.
AD Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106-4901, USA
SP englisch
PO USA