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. 2025 Aug 13.
doi: 10.1007/s13353-025-01000-3. Online ahead of print.

Prevalence of intronic repeat expansions in the RFC1 gene in Polish patients with cerebellar syndrome

Tomczuk Filip  1 , Ziora-Jakutowicz Karolina  2 , Dominik Natalia  3 , Houlden Henry  3 , Cortese Andrea  3   4 , Rutkowska Karolina  5 , Pollak Agnieszka  5 , Ploski Rafal  5 , Janik Piotr  6 , Elert-Dobkowska Ewelina  7 , Sulek Anna  8
Affiliations

Prevalence of intronic repeat expansions in the RFC1 gene in Polish patients with cerebellar syndrome

Tomczuk Filip et al. J Appl Genet. .

Abstract

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative ataxic disorder, which has been associated with intronic biallelic repeat expansions in the RFC1 gene. Our objective was to assess retrospectively the prevalence of CANVAS in Polish population. We screened 2523 Polish patients in whom other repeat expansions were excluded. To determine the repeat expansions in the RFC1 gene in patients, we performed RFC1-flanking PCR and repeat primed PCR (RP-PCR) and to measure the size of the expansion we used Southern blotting and optical genome mapping to compare the results. We have observed the biallelic pathogenic motif/unit AAGGG expansions in 4.6% and expansions of non-pathogenic motifs AAAAG, AAAGG in 25% patients of our studied population. This is the first large-scale cohort study that confirms the relatively frequent occurrence of the CANVAS in Polish population. To increase the current diagnostics of late-onset ataxias within an unexplained molecular background, we suggest involving the RFC1 repeat expansions analysis to the routine diagnostic workflow.

Keywords: RFC1; Adult-onset ataxia; CANVAS; Optical genome mapping; Repeat expansion.

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Conflict of interest statement

Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institute of Psychiatry and Neurology Ethics Committee no. 30/2021. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests.

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