University of Oulu

Lipponen, J., Helisalmi, S., Raivo, J. et al. Molecular epidemiology of hereditary ataxia in Finland. BMC Neurol 21, 382 (2021).

Molecular epidemiology of hereditary ataxia in Finland

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Author: Lipponen, Joonas1,2; Helisalmi, Seppo3; Raivo, Joose3;
Organizations: 1Research Unit of Clinical Neuroscience, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
2Department of Neurology, Oulu University Hospital, Oulu, Finland
3Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
4Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-11-23


Background: The genetics of cerebellar ataxia is complex. Hundreds of causative genes have been identified, but only a few cause more than single cases. The spectrum of ataxia-causing genes differs considerably between populations. The aim of the study was to investigate the molecular epidemiology of ataxia in the Finnish population.

Patients and methods: All patients in hospital database were reviewed for the diagnosis of unspecified ataxia. Acquired ataxias and nongenetic ataxias such as those related to infection, trauma or stroke were excluded. Sixty patients with sporadic ataxia with unknown etiology and 36 patients with familial ataxia of unknown etiology were recruited in the study. Repeat expansions in the SCA genes (ATXN1, 2, 3, 7, 8/OS, CACNA1A, TBP), FXN, and RFC1 were determined. Point mutations in POLG, SPG7 and in mitochondrial DNA (mtDNA) were investigated. In addition, DNA from 8 patients was exome sequenced.

Results: A genetic cause of ataxia was found in 33 patients (34.4%). Seven patients had a dominantly inherited repeat expansion in ATXN8/OS. Ten patients had mitochondrial ataxia resulting from mutations in nuclear mitochondrial genes POLG or RARS2, or from a point mutation m.8561C > G or a single deletion in mtDNA. Interestingly, five patients were biallelic for the recently identified pathogenic repeat expansion in RFC1. All the five patients presented with the phenotype of cerebellar ataxia, neuropathy, and vestibular areflexia (CANVAS). Moreover, screening of 54 patients with Charcot-Marie-Tooth neuropathy revealed four additional patients with biallelic repeat expansion in RFC1, but none of them had cerebellar symptoms.

Conclusions: Expansion in ATXN8/OS results in the majority of dominant ataxias in Finland, while mutations in RFC1 and POLG are the most common cause of recessive ataxias. Our results suggest that analysis of RFC1 should be included in the routine diagnostics of idiopathic ataxia and Charcot-Marie-Tooth polyneuropathy.

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Series: BMC neurology
ISSN: 1471-2377
ISSN-E: 1471-2377
ISSN-L: 1471-2377
Volume: 21
Issue: 1
Article number: 382
DOI: 10.1186/s12883-021-02409-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: The study was funded by grants from the Sigrid Jusélius Foundation and from the Medical Research Center Oulu. The study received state research funding from Oulu University Hospital. The funders did not have any influence on the results of this study.
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