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 (<i>PRNP</i>) 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 V180...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/18/10210 |
| _version_ | 1797487538424774656 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Gianluigi Zanusso |
| collection | DOAJ |
| description | Genetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (<i>PRNP</i>) 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<sup>Sc</sup>) 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. |
| first_indexed | 2024-03-09T23:50:05Z |
| format | Article |
| id | doaj.art-d9c083d816cb4166ade3f9c43dd04b42 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:50:05Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d9c083d816cb4166ade3f9c43dd04b422023-11-23T16:37:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181021010.3390/ijms231810210Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein GeneGianluigi Zanusso0Elisa Colaizzo1Anna Poleggi2Carlo Masullo3Raffaello Romeo4Sergio Ferrari5Matilde Bongianni6Michele Fiorini7Dorina Tiple8Luana Vaianella9Marco Sbriccoli10Flavia Porreca11Michele Equestre12Maurizio Pocchiari13Franco Cardone14Anna Ladogana15Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Catholic University of the Sacred Heart, 00168 Rome, ItalyUnit of Otolaryngology, Clinica Nuova Itor Rome, 00158 Rome, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyGenetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (<i>PRNP</i>) 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<sup>Sc</sup>) 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.https://www.mdpi.com/1422-0067/23/18/10210Creutzfeldt–Jakob diseaseprion diseaseneuropathologyprion proteinVal180Ile mutationRT-QuIC assay |
| spellingShingle | 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 Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene International Journal of Molecular Sciences Creutzfeldt–Jakob disease prion disease neuropathology prion protein Val180Ile mutation RT-QuIC assay |
| 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 | Creutzfeldt–Jakob disease prion disease neuropathology prion protein Val180Ile mutation RT-QuIC assay |
| url | https://www.mdpi.com/1422-0067/23/18/10210 |
| work_keys_str_mv | AT gianluigizanusso biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT elisacolaizzo biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT annapoleggi biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT carlomasullo biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT raffaelloromeo biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT sergioferrari biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT matildebongianni biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT michelefiorini biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT dorinatiple biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT luanavaianella biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT marcosbriccoli biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT flaviaporreca biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT micheleequestre biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT mauriziopocchiari biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT francocardone biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene AT annaladogana biochemicalandneuropathologicalfindingsinacreutzfeldtjakobdiseasepatientwiththerareval180ile129valhaplotypeintheprionproteingene |