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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8473248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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