A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report
Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) confor...
| Autores: | , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2010 |
| País: | España |
| Recursos: | Universidad del País Vasco |
| Repositorio: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/11885 |
| Acesso em linha: | http://hdl.handle.net/10810/11885 |
| Access Level: | acceso abierto |
| Palavra-chave: | Creutzfeldt-Jakob disease Straussler-Scheinker disease fatal familial insomnia phenotypic variability DNA polymorphism classification NEUROLOGY |
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A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case reportRodríguez Martínez, Ana B.Garrido Urkullu, Joseba M.Zarranz Imirizaldu, Juan JoséArteagoitia, Jose M.Martínez de Pancorbo Gómez, María de los AngelesAtares, BegonaBilbao, Miren J.Ferrer, IsidroJuste Jordán, Ramón A.Creutzfeldt-Jakob diseaseStraussler-Scheinker diseasefatal familial insomniaphenotypic variabilityDNA polymorphismclassificationNEUROLOGYBackground: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.Supported By a Health Research grant from the Planning and Arranging Director of the Department of Health of the Basque Government (grant #2006111037).BioMed Central201420142010info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/11885reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttp://www.biomedcentral.com/1471-2377/10/99info:eu-repo/semantics/openAccess© 2010 Rodríguez-Martínez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.oai:addi.ehu.eus:10810/118852026-06-18T09:23:17Z |
| dc.title.none.fl_str_mv |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| title |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| spellingShingle |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report Rodríguez Martínez, Ana B. Creutzfeldt-Jakob disease Straussler-Scheinker disease fatal familial insomnia phenotypic variability DNA polymorphism classification NEUROLOGY |
| title_short |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| title_full |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| title_fullStr |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| title_full_unstemmed |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| title_sort |
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report |
| dc.creator.none.fl_str_mv |
Rodríguez Martínez, Ana B. Garrido Urkullu, Joseba M. Zarranz Imirizaldu, Juan José Arteagoitia, Jose M. Martínez de Pancorbo Gómez, María de los Angeles Atares, Begona Bilbao, Miren J. Ferrer, Isidro Juste Jordán, Ramón A. |
| author |
Rodríguez Martínez, Ana B. |
| author_facet |
Rodríguez Martínez, Ana B. Garrido Urkullu, Joseba M. Zarranz Imirizaldu, Juan José Arteagoitia, Jose M. Martínez de Pancorbo Gómez, María de los Angeles Atares, Begona Bilbao, Miren J. Ferrer, Isidro Juste Jordán, Ramón A. |
| author_role |
author |
| author2 |
Garrido Urkullu, Joseba M. Zarranz Imirizaldu, Juan José Arteagoitia, Jose M. Martínez de Pancorbo Gómez, María de los Angeles Atares, Begona Bilbao, Miren J. Ferrer, Isidro Juste Jordán, Ramón A. |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
Creutzfeldt-Jakob disease Straussler-Scheinker disease fatal familial insomnia phenotypic variability DNA polymorphism classification NEUROLOGY |
| topic |
Creutzfeldt-Jakob disease Straussler-Scheinker disease fatal familial insomnia phenotypic variability DNA polymorphism classification NEUROLOGY |
| description |
Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones. |
| publishDate |
2010 |
| dc.date.none.fl_str_mv |
2010 2014 2014 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10810/11885 |
| url |
http://hdl.handle.net/10810/11885 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
http://www.biomedcentral.com/1471-2377/10/99 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
BioMed Central |
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BioMed Central |
| dc.source.none.fl_str_mv |
reponame:Addi. Archivo Digital para la Docencia y la Investigación instname:Universidad del País Vasco |
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Universidad del País Vasco |
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Addi. Archivo Digital para la Docencia y la Investigación |
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Addi. Archivo Digital para la Docencia y la Investigación |
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