A three-sister sibship of Gerstmann-Sträussler-Scheinker disease with a CJD phenotype

Abstract

The authors report the second recorded example of a sporadic CJD phenotype occurring in association with the P102L GSS genotype, and the first instance in which the phenotype was the rule rather than the exception, or was associated with prominent beta-A4 plaque formation.

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

“…Rather, GSS patients with CJD features are more likely to have PSIDDs [3,8,25,[42][43][44]. The EEG features of our patient 2 (IV-3) and patient 3 (V-2) at late disease stages corroborated this point of view.…”

“…P102L has also been documented in other families of different ethnicities [2,13,17,22,25,36,42,44] and is the most common mutation associated with GSS [8,9,11,17,21]. The disease is characterized pathologically by the deposition of multicentric amyloid-like plaques with a positive PrP immunoreactivity in the brain [4,27] and clinically by variable, progressive cerebellar ataxia or dementia in a relatively prolonged course (mean duration of illness: 5-7 years) [8,9,27].…”

Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

“…Expression of mutated PrP encompassing two, five and nine additional octarepeats in the bait position versus wild-type PrP in the prey position of the yeast two-hybrid system slightly diminished the PrP/PrP interaction process. This situation mimics heterozygous CJD patients with the mutated Prn-p gene on one allele and the wild-type Prn-p on the other (Majtenyi et al, 2000). Expression of mutated PrP with five and nine additional octarepeats in both positions of the yeast two-hybrid system resulted in total inhibition of the PrP/PrP interaction, reflecting to our knowledge a hypothetical homozygous CJD patient expressing this mutated PrP on both alleles of the Prn-p gene.…”

“…fCJD patients encompassing two (Goldfarb et al, 1993), four (Campbell et al, 1996), five (Goldfarb et al, 1991), six (Owen et al, 1990), seven (Goldfarb et al, 1991), eight (Goldfarb et al, 1991) and nine additional octarepeats (Owen et al, 1992) have been described. All these patients are heterozygous regarding these mutations (Majtenyi et al, 2000). The mutation proline 102 to leucine leads to GSS (Goldgaber et al, 1989).…”

Molecular Genetics of Gerstmann-Straussler-Scheinker Disease and Creutzfeld-Jakob Disease

“…This mutation was subsequently found in several families from Japan [65][66][67][68][69][70][71], Germany [72,73] -in the well described Sch. family [74][75][76][77], Israel [78], Hungary [79], Poland [80], UK [81,82], Italy [83][84][85] and in the original Viennese "H" family [86]. Japanese cases are interesting, as before the era of molecular biology they were regarded as CJD cases with abundant plaques [87] while in reality these were GSS cores.…”