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Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat...

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Autores principales: Brennecke, Nicholas, Cali, Ignazio, Mok, Tze How, Speedy, Helen, Hosszu, Laszlo L. P., Stehmann, Christiane, Cracco, Laura, Puoti, Gianfranco, Prior, Thomas W., Cohen, Mark L., Collins, Steven J., Mead, Simon, Appleby, Brian S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473248/
https://www.ncbi.nlm.nih.gov/pubmed/34578375
http://dx.doi.org/10.3390/v13091794
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author Brennecke, Nicholas
Cali, Ignazio
Mok, Tze How
Speedy, Helen
Hosszu, Laszlo L. P.
Stehmann, Christiane
Cracco, Laura
Puoti, Gianfranco
Prior, Thomas W.
Cohen, Mark L.
Collins, Steven J.
Mead, Simon
Appleby, Brian S.
author_facet Brennecke, Nicholas
Cali, Ignazio
Mok, Tze How
Speedy, Helen
Hosszu, Laszlo L. P.
Stehmann, Christiane
Cracco, Laura
Puoti, Gianfranco
Prior, Thomas W.
Cohen, Mark L.
Collins, Steven J.
Mead, Simon
Appleby, Brian S.
author_sort Brennecke, Nicholas
collection PubMed
description Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk.
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spelling pubmed-84732482021-09-28 Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion Brennecke, Nicholas Cali, Ignazio Mok, Tze How Speedy, Helen Hosszu, Laszlo L. P. Stehmann, Christiane Cracco, Laura Puoti, Gianfranco Prior, Thomas W. Cohen, Mark L. Collins, Steven J. Mead, Simon Appleby, Brian S. Viruses Article Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk. MDPI 2021-09-08 /pmc/articles/PMC8473248/ /pubmed/34578375 http://dx.doi.org/10.3390/v13091794 Text en © 2021 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
Brennecke, Nicholas
Cali, Ignazio
Mok, Tze How
Speedy, Helen
Hosszu, Laszlo L. P.
Stehmann, Christiane
Cracco, Laura
Puoti, Gianfranco
Prior, Thomas W.
Cohen, Mark L.
Collins, Steven J.
Mead, Simon
Appleby, Brian S.
Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title_full Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title_fullStr Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title_full_unstemmed Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title_short Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion
title_sort characterization of prion disease associated with a two-octapeptide repeat insertion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473248/
https://www.ncbi.nlm.nih.gov/pubmed/34578375
http://dx.doi.org/10.3390/v13091794
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