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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9499355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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