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. 2024 Mar;95(3):607-613.
doi: 10.1002/ana.26848. Epub 2023 Dec 27.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers

Taishi Wada  1 , Hiroshi Doi  1 , Masaki Okubo  1 , Mikiko Tada  1 , Naohisa Ueda  2 , Hidefumi Suzuki  3 , Wakana Tominaga  1 , Haruki Koike  4 , Hiroyasu Komiya  1 , Shun Kubota  1 , Shunta Hashiguchi  1 , Haruko Nakamura  1 , Keita Takahashi  1 , Misako Kunii  1 , Kenichi Tanaka  1 , Yosuke Miyaji  1 , Yuichi Higashiyama  1 , Eriko Koshimizu  5 , Satoko Miyatake  5   6 , Masahisa Katsuno  4   7 , Satoshi Fujii  8 , Hidehisa Takahashi  3 , Naomichi Matsumoto  5 , Hideyuki Takeuchi  1 , Fumiaki Tanaka  1
Affiliations

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers

Taishi Wada et al. Ann Neurol. 2024 Mar.

Abstract

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.

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