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Título:
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Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease
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Autor/a:
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Gelpi, Ellen; Baiardi, Simone; Nos Llopis, Carlos; Dellavalle, Sofia; Aldecoa, Iban; Ruiz-García, Raquel; Barranco, Elena; Boltes, Anuncia
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Otros autores:
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[Gelpi E] Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna and Austrian Reference Center for Human Prion Diseases (ÖRPE), AKH Leitstelle 4J, Vienna, Austria. Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain. [Baiardi S] IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. [Nos C] General Subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain. [Dellavalle S] IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. [Aldecoa I] Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain. Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain. [Ruiz-Garcia R] Department of Pathology, Center for Biomedical Diagnosis, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain. [Barranco E] Department of Geriatrics, Hospital General de Granollers, Granollers, Spain. [Boltes A] Department of Neurology, Hospital General de Granollers, Granollers, Spain; Hospital General de Granollers |
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Abstract:
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Creutzfeldt-Jakob disease; Prion disease; Prion strains |
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Abstract:
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Malaltia de Creutzfeldt-Jakob; Malalties priòniques; Soques de prions |
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Abstract:
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Enfermedad de Creutzfeldt-Jakob; Enfermedad priónica; Cepas de priones |
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Abstract:
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The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype. |
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Materia(s):
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-Creutzfeldt-Jakob, Malaltia de
-Malalties priòniques
-Genètica
-DISEASES::Nervous System Diseases::Central Nervous System Diseases::Nervous System Diseases::Central Nervous System Diseases::Central Nervous System Infections::Prion Diseases::Creutzfeldt-Jakob Syndrome
-CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::GPI-Linked Proteins::Prion Proteins
-CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger::Codon
-ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::infecciones del sistema nervioso central::enfermedades por priones::síndrome de Creutzfeldt-Jakob
-COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::glicoproteínas::glicoproteínas de membranas::proteínas ligadas a GPI::proteínas priónicas
-COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN mensajero::codón |
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Derechos:
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Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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Tipo de documento:
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Artículo
Artículo - Versión publicada |
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Editor:
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BMC
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