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Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene

Authors :
Gianluigi Zanusso
Elisa Colaizzo
Anna Poleggi
Carlo Masullo
Raffaello Romeo
Sergio Ferrari
Matilde Bongianni
Michele Fiorini
Dorina Tiple
Luana Vaianella
Marco Sbriccoli
Flavia Porreca
Michele Equestre
Maurizio Pocchiari
Franco Cardone
Anna Ladogana
Source :
International Journal of Molecular Sciences, Vol 23, Iss 18, p 10210 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Genetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
18
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.9c083d816cb4166ade3f9c43dd04b42
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms231810210