NR ALIM
AU Tagliavini,F.; Prelli,F.; Porro,M.; Rossi,G.; Giaccone,G.; Farlow,M.R.; Dlouhy,S.R.; Ghetti,B.; Bugiani,O.; Frangione,B.
TI Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele
QU Cell 1994 Nov 18; 79(4): 695-703
PT journal article
AB Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene. We previously reported that the amyloid protein in the Indiana kindred of GSS is an internal fragment of prion protein (PrP). To investigate whether this fragment originates only from mutant or from both mutant and wild-type PrP, we have characterized amyloid proteins purified from patients of the Indiana and Swedish GSS families. These patients were heterozygous for the Met-Val polymorphism at PRNP codon 129 and carried a mutation at PRNP codon 198 (Phe -> Ser) and codon 217 (Gln -> Arg), respectively. The smallest amyloid subunit was a 7 kDa peptide spanning residues approximately 81 to approximately 150 in the Indiana patient and approximately 81 to approximately 146 in the Swedish patient. In both patients, only Val was present at position 129. Since Val-129 was in coupling phase with Ser-198 and Arg-217, our findings indicate that only the mutant PrP is involved in amyloid formation in both kindreds.
IN Gerstmann-Sträussler-Scheinker-Patienten aus 2 Familien waren heterozygot bezüglich des Prionproteincodons 129, wo die Allele Methionin oder Valin aufweisen. Jeweils das Valin-Allel besitzt zusätzlich eine krankmachende Mutation. Dies ist in der einen Familie eine Mutation Phenylalanin zu Serin in Codon 198 und in der anderen Familie eine Mutation Glutamin zu Arginin in Codon 217. In den amyloiden Fibrillen wurden ausschließlich Fragmente der mutierten Valin-Variante gefunden.
ZR 51
MH Amino Acid Sequence; Amyloid/*biosynthesis/genetics/isolation & purification; Base Sequence; Case Report; Chromatography, Gel; Chromatography, High Pressure Liquid; Codon/genetics; DNA Primers; Genotype; Gerstmann-Sträussler-Scheinker Disease/*genetics/metabolism; Human; Immunoblotting; Indiana; Molecular Sequence Data; Peptide Fragments/chemistry/isolation & purification; *Point Mutation; Polymerase Chain Reaction; Prions/*biosynthesis/*genetics/isolation & purification; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Sweden
AD Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
SP englisch
PO USA