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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

C9orf72 Protein*/genetics ; Multiple Sclerosis*/genetics; Humans ; Amyotrophic Lateral Sclerosis/genetics ; Austria ; Frontotemporal Dementia/genetics ; Multiple Sclerosis, Chronic Progressive/genetics ; Retrospective Studies

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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Keywords: C9orf72 repeat expansion; disease heterogeneity; frontotemporal dementia (FTD); genetic variants; intermediate repeat length; multiple sclerosis (MS)

0 (C9orf72 Protein)
0 (C9orf72 protein, human)

Date Created: 20230729 Date Completed: 20230807 Latest Revision: 20230807

20231215

PMC10378763

10.3390/ijms241411254

37511014