Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene
Abstract Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-01-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-018-0656-4 |
| _version_ | 1798045830638206976 |
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| author | Giuseppe Di Fede Marcella Catania Cristiana Atzori Fabio Moda Claudio Pasquali Antonio Indaco Marina Grisoli Marta Zuffi Maria Cristina Guaita Roberto Testi Stefano Taraglio Maria Sessa Graziano Gusmaroli Mariacarmela Spinelli Giulia Salzano Giuseppe Legname Roberto Tarletti Laura Godi Maurizio Pocchiari Fabrizio Tagliavini Daniele Imperiale Giorgio Giaccone |
| author_facet | Giuseppe Di Fede Marcella Catania Cristiana Atzori Fabio Moda Claudio Pasquali Antonio Indaco Marina Grisoli Marta Zuffi Maria Cristina Guaita Roberto Testi Stefano Taraglio Maria Sessa Graziano Gusmaroli Mariacarmela Spinelli Giulia Salzano Giuseppe Legname Roberto Tarletti Laura Godi Maurizio Pocchiari Fabrizio Tagliavini Daniele Imperiale Giorgio Giaccone |
| author_sort | Giuseppe Di Fede |
| collection | DOAJ |
| description | Abstract Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85–90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10–15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases. We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrPSc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrPres), and type 1 PrPres was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD. Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrPSc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes. |
| first_indexed | 2024-04-11T23:27:27Z |
| format | Article |
| id | doaj.art-46afdf2fd23547ffa41d811b6d180715 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-11T23:27:27Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-46afdf2fd23547ffa41d811b6d1807152022-12-22T03:57:15ZengBMCActa Neuropathologica Communications2051-59602019-01-017111110.1186/s40478-018-0656-4Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein geneGiuseppe Di Fede0Marcella Catania1Cristiana Atzori2Fabio Moda3Claudio Pasquali4Antonio Indaco5Marina Grisoli6Marta Zuffi7Maria Cristina Guaita8Roberto Testi9Stefano Taraglio10Maria Sessa11Graziano Gusmaroli12Mariacarmela Spinelli13Giulia Salzano14Giuseppe Legname15Roberto Tarletti16Laura Godi17Maurizio Pocchiari18Fabrizio Tagliavini19Daniele Imperiale20Giorgio Giaccone21Neurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaNeurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaCentro Regionale Malattie da Prioni (DOMP), ASL ‘Città di Torino’Neurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaNeurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaNeurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaNeuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaNeurology Unit, MultimedicaNeurology Unit, AO Ospedale Civile di LegnanoCentro Regionale Malattie da Prioni (DOMP), ASL ‘Città di Torino’Centro Regionale Malattie da Prioni (DOMP), ASL ‘Città di Torino’Neurology Unit, Foundation IRCCS Centro s. Raffaele del Monte TaborNeurology Unit, ASL BiellaNeurology Unit, Humanitas Clinical Institute RozzanoLaboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA)Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA)Neurology Unit, Osp. Maggiore della CaritàNeurology Unit, ASL Novara, Ospedale di BorgomaneroDepartment of Neuroscience, Istituto Superiore di SanitàScientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo BestaCentro Regionale Malattie da Prioni (DOMP), ASL ‘Città di Torino’Neurology V – Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo BestaAbstract Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85–90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10–15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases. We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrPSc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrPres), and type 1 PrPres was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD. Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrPSc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.http://link.springer.com/article/10.1186/s40478-018-0656-4Creutzfeldt-Jakob diseasePRNPPrionV189ICJDPrP |
| spellingShingle | Giuseppe Di Fede Marcella Catania Cristiana Atzori Fabio Moda Claudio Pasquali Antonio Indaco Marina Grisoli Marta Zuffi Maria Cristina Guaita Roberto Testi Stefano Taraglio Maria Sessa Graziano Gusmaroli Mariacarmela Spinelli Giulia Salzano Giuseppe Legname Roberto Tarletti Laura Godi Maurizio Pocchiari Fabrizio Tagliavini Daniele Imperiale Giorgio Giaccone Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene Acta Neuropathologica Communications Creutzfeldt-Jakob disease PRNP Prion V189I CJD PrP |
| title | Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene |
| title_full | Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene |
| title_fullStr | Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene |
| title_full_unstemmed | Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene |
| title_short | Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene |
| title_sort | clinical and neuropathological phenotype associated with the novel v189i mutation in the prion protein gene |
| topic | Creutzfeldt-Jakob disease PRNP Prion V189I CJD PrP |
| url | http://link.springer.com/article/10.1186/s40478-018-0656-4 |
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