title: Gerstmann-Sträussler-Scheinker: a new phenotype with 'curly' PrP deposits.
abstract: Gerstmann-Sträussler-Scheinker (GSS) is a hereditary prion disease typically associated with prion protein (PrP)-containing plaques. The protease-resistant, scrapie PrP (PrPSc) is represented by internal fragments, whereas the C-terminal fragments associated with the other prion diseases are generally underrepresented. Different histopathologic and PrPSc features associated with at least 13 PrP gene (PRNP) mutations have been described in GSS. We report the histopathology and PrP characteristics in a father and son carrying a mutation at PRNP codon 187 that substitutes histidine (H) with arginine (R) and is coupled with valine (V) at position 129 (H187R-129V). The PrP plaques were present in both cases but with different structure and topography and minimal spongiform degeneration. A distinctive, "curly" PrP immunostaining was prominent in one case. The protease-resistant PrPSc differed in amount in the 2 cases, possibly depending on whether plaques or the curly immunostain was present. Two protease-resistant PrP fragments of 14 kDa and 7 kDa with, in at least one case, N-terminus between residues 90-99 and 82-90, respectively, codistributed with the plaques, whereas only very small amounts of the PK-resistant PrP were present in the curly staining regions. PK-resistant PrP recovered from the plaque and curly staining regions appeared to be full length.
authors.affiliation: Department of Neurology, University of Genoa, Genoa, Italy, and Pikeville Neurology Clinic and Diagnostic Center, Pikeville, Kentucky, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Colucci
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Moleres
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Xie
authors.forename: Abhik
authors.initials: A
authors.lastname: Ray-Chaudhury
authors.forename: Sujata
authors.initials: S
authors.lastname: Gutti
authors.forename: Cathrin M
authors.initials: CM
authors.lastname: Butefisch
authors.forename: Larisa
authors.initials: L
authors.lastname: Cervenakova
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Lev G
authors.initials: LG
authors.lastname: Goldfarb
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Shu G
authors.initials: SG
authors.lastname: Chen
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017354:Point Mutation; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D018620:PrPSc Proteins