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No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort

Multiple Sclerosis (MS) is a common immune-mediated disorder of the central nervous system that affects young adults and is characterized by demyelination and neurodegeneration. Recent studies have associated C9orf72 intermediate repeat expansions with MS. The objective of this study was to investig...

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Autores principales: König, Theresa, Leutmezer, Fritz, Berger, Thomas, Zimprich, Alexander, Schmied, Christiane, Stögmann, Elisabeth, Zrzavy, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378763/
https://www.ncbi.nlm.nih.gov/pubmed/37511014
http://dx.doi.org/10.3390/ijms241411254
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author König, Theresa
Leutmezer, Fritz
Berger, Thomas
Zimprich, Alexander
Schmied, Christiane
Stögmann, Elisabeth
Zrzavy, Tobias
author_facet König, Theresa
Leutmezer, Fritz
Berger, Thomas
Zimprich, Alexander
Schmied, Christiane
Stögmann, Elisabeth
Zrzavy, Tobias
author_sort König, Theresa
collection PubMed
description Multiple Sclerosis (MS) is a common immune-mediated disorder of the central nervous system that affects young adults and is characterized by demyelination and neurodegeneration. Recent studies have associated C9orf72 intermediate repeat expansions with MS. The objective of this study was to investigate whether C9orf72 repeat length is associated with MS or with a specific disease course in a monocentric Austrian MS cohort. Genotyping of 382 MS patients and 643 non-neurological controls for C9orf72 repeat expansions was performed. The study did not find a difference in the distribution of repeat numbers between controls and MS cases (median repeat units = 2; p = 0.39). Additionally, sub-analysis did not establish a link between intermediate repeats and MS (p = 0.23) and none of the patients with progressive disease course carried an intermediate allele (20–30 repeat units). Exploratory analysis for different cut-offs (of ≥7, ≥17, and ≥24) did not reveal any significant differences in allele frequencies between MS and controls. However, the study did identify a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing behavioral variant frontotemporal dementia (bvFTD) in a retrospective chart review. In conclusion, this study did not find evidence supporting an association between C9orf72 repeat length and MS or a specific disease course in the Austrian MS cohort. However, the identification of a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing with FTD highlights the complexity and challenges involved in recognizing distinct neurodegenerative diseases that may co-occur in MS patients.
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spelling pubmed-103787632023-07-29 No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort König, Theresa Leutmezer, Fritz Berger, Thomas Zimprich, Alexander Schmied, Christiane Stögmann, Elisabeth Zrzavy, Tobias Int J Mol Sci Communication Multiple Sclerosis (MS) is a common immune-mediated disorder of the central nervous system that affects young adults and is characterized by demyelination and neurodegeneration. Recent studies have associated C9orf72 intermediate repeat expansions with MS. The objective of this study was to investigate whether C9orf72 repeat length is associated with MS or with a specific disease course in a monocentric Austrian MS cohort. Genotyping of 382 MS patients and 643 non-neurological controls for C9orf72 repeat expansions was performed. The study did not find a difference in the distribution of repeat numbers between controls and MS cases (median repeat units = 2; p = 0.39). Additionally, sub-analysis did not establish a link between intermediate repeats and MS (p = 0.23) and none of the patients with progressive disease course carried an intermediate allele (20–30 repeat units). Exploratory analysis for different cut-offs (of ≥7, ≥17, and ≥24) did not reveal any significant differences in allele frequencies between MS and controls. However, the study did identify a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing behavioral variant frontotemporal dementia (bvFTD) in a retrospective chart review. In conclusion, this study did not find evidence supporting an association between C9orf72 repeat length and MS or a specific disease course in the Austrian MS cohort. However, the identification of a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing with FTD highlights the complexity and challenges involved in recognizing distinct neurodegenerative diseases that may co-occur in MS patients. MDPI 2023-07-09 /pmc/articles/PMC10378763/ /pubmed/37511014 http://dx.doi.org/10.3390/ijms241411254 Text en © 2023 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 Communication
König, Theresa
Leutmezer, Fritz
Berger, Thomas
Zimprich, Alexander
Schmied, Christiane
Stögmann, Elisabeth
Zrzavy, Tobias
No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title_full No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title_fullStr No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title_full_unstemmed No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title_short No Association of Multiple Sclerosis with C9orf72 Hexanucleotide Repeat Size in an Austrian Cohort
title_sort no association of multiple sclerosis with c9orf72 hexanucleotide repeat size in an austrian cohort
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378763/
https://www.ncbi.nlm.nih.gov/pubmed/37511014
http://dx.doi.org/10.3390/ijms241411254
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