University of Oulu

Korpioja, A., Krüger, J., Hurme-Niiranen, A., Solje, E., Katisko, K., Lipponen, J., Lehtilahti, M., Remes, A. M., Majamaa, K., & Kytövuori, L. (2022). Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease. Parkinsonism & Related Disorders, 103, 98–101.

Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

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Author: Korpioja, Anita1,2; Krüger, Johanna1,2,3; Hurme-Niiranen, Anri1,2;
Organizations: 1Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
2MRC, Oulu University Hospital and University of Oulu, Oulu, Finland
3OUH Neurocenter, Neurology, Oulu University Hospital, FI-90029, Oulu, Finland
4KUH NeuroCenter, Neurology, Kuopio University Hospital, P.O. Box 100, 70029, KYS, Kuopio, Finland
5Institute of Clinical Medicine - Neurology, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland
6Clinical Neurosciences, University of Helsinki, Biomedicum, P.O. Box 63, 00014, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2023-06-16


Introduction: The biallelic repeat expansion (AAGGG)exp in RFC1 causes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recently, cognitive impairment has been reported in patients with CANVAS and a broader neurodegenerative process associated with RFC1 has been suggested. Furthermore, rare cases of multiple system atrophy, Parkinson’s disease, amyotrophic lateral sclerosis or CANVAS with features of dementia with Lewy bodies have been found.

Objective: We hypothesized that the biallelic (AAGGG)exp is associated with neurodegeneration manifested as cognitive symptoms and that atypical RFC1 disease may be found among patients with cognitive disorder.

Methods: Clinical data on nine patients with biallelic (AAGGG)exp were reviewed and 564 patients with Alzheimer’s disease or frontotemporal dementia (FTD) were investigated for biallelic RFC1 (AAGGG)exp.

Results: Five patients with biallelic (AAGGG)exp were found with a cognitive impairment and in four of them the phenotype resembled FTD. However, biallelic (AAGGG)exp was not detected among patients with Alzheimer’s disease or FTD.

Conclusions: Cognitive impairment is a feature in patients with the biallelic (AAGGG)exp, but the pathogenic expansion seems to be rare in patients with dementia. Studies on patients with diverse phenotypes would be useful to further explore the involvement of RFC1 in neuronal degeneration and to identify atypical phenotypes, which should be taken into account in clinical practice.

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Series: Parkinsonism & related disorders
ISSN: 1353-8020
ISSN-E: 1873-5126
ISSN-L: 1353-8020
Volume: 103
Pages: 98 - 101
DOI: 10.1016/j.parkreldis.2022.08.034
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This work was supported by grants from the Academy of Finland [315459], from the Sigrid Jusélius Foundation, from the Finnish Medical Foundation and from the Yrjö Jahnsson Foundation. The study received funding from Medical Research Center Oulu and State Research funding from Oulu University Hospital.
Copyright information: © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (