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: Monica Colucci, Francisco J Moleres, Zhi-Liang Xie, Abhik Ray-Chaudhury, Sujata Gutti, Cathrin M Butefisch, Larisa Cervenakova, Wen Wang, Lev G Goldfarb, Qingzhong Kong, Bernardino Ghetti, Shu G Chen, Pierluigi Gambetti
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 65 Issue 7 Pg. 642-51 (Jul 2006) ISSN: 0022-3069 [Print] England
• PMID: 16825951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Peptide Fragments
• PrPSc Proteins

Topics

• Adult
• Amino Acid Sequence
• Animals
• Brain (anatomy & histology, metabolism, pathology)
• Gerstmann-Straussler-Scheinker Disease (genetics, pathology)
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Peptide Fragments (genetics, metabolism)
• Phenotype
• Point Mutation
• PrPSc Proteins (genetics, metabolism)