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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

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, s...

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Autores principales: Zanusso, Gianluigi, Colaizzo, Elisa, Poleggi, Anna, Masullo, Carlo, Romeo, Raffaello, Ferrari, Sergio, Bongianni, Matilde, Fiorini, Michele, Tiple, Dorina, Vaianella, Luana, Sbriccoli, Marco, Porreca, Flavia, Equestre, Michele, Pocchiari, Maurizio, Cardone, Franco, Ladogana, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499355/
https://www.ncbi.nlm.nih.gov/pubmed/36142123
http://dx.doi.org/10.3390/ijms231810210
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author Zanusso, Gianluigi
Colaizzo, Elisa
Poleggi, Anna
Masullo, Carlo
Romeo, Raffaello
Ferrari, Sergio
Bongianni, Matilde
Fiorini, Michele
Tiple, Dorina
Vaianella, Luana
Sbriccoli, Marco
Porreca, Flavia
Equestre, Michele
Pocchiari, Maurizio
Cardone, Franco
Ladogana, Anna
author_facet Zanusso, Gianluigi
Colaizzo, Elisa
Poleggi, Anna
Masullo, Carlo
Romeo, Raffaello
Ferrari, Sergio
Bongianni, Matilde
Fiorini, Michele
Tiple, Dorina
Vaianella, Luana
Sbriccoli, Marco
Porreca, Flavia
Equestre, Michele
Pocchiari, Maurizio
Cardone, Franco
Ladogana, Anna
author_sort Zanusso, Gianluigi
collection PubMed
description 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 (PrP(Sc)) 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.
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spelling pubmed-94993552022-09-23 Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene Zanusso, Gianluigi Colaizzo, Elisa Poleggi, Anna Masullo, Carlo Romeo, Raffaello Ferrari, Sergio Bongianni, Matilde Fiorini, Michele Tiple, Dorina Vaianella, Luana Sbriccoli, Marco Porreca, Flavia Equestre, Michele Pocchiari, Maurizio Cardone, Franco Ladogana, Anna Int J Mol Sci Article 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 (PrP(Sc)) 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. MDPI 2022-09-06 /pmc/articles/PMC9499355/ /pubmed/36142123 http://dx.doi.org/10.3390/ijms231810210 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zanusso, Gianluigi
Colaizzo, Elisa
Poleggi, Anna
Masullo, Carlo
Romeo, Raffaello
Ferrari, Sergio
Bongianni, Matilde
Fiorini, Michele
Tiple, Dorina
Vaianella, Luana
Sbriccoli, Marco
Porreca, Flavia
Equestre, Michele
Pocchiari, Maurizio
Cardone, Franco
Ladogana, Anna
Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title_full Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title_fullStr Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title_full_unstemmed Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title_short Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene
title_sort biochemical and neuropathological findings in a creutzfeldt–jakob disease patient with the rare val180ile-129val haplotype in the prion protein gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499355/
https://www.ncbi.nlm.nih.gov/pubmed/36142123
http://dx.doi.org/10.3390/ijms231810210
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