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. 2023 Oct 18;13(1):17801.
doi: 10.1038/s41598-023-45011-8.

CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy

Makito Hirano  1 , Motoi Kuwahara  2 , Yuko Yamagishi  2 , Makoto Samukawa  2 , Kanako Fujii  2 , Shoko Yamashita  2 , Masahiro Ando  3 , Nobuyuki Oka  4 , Mamoru Nagano  5 , Taro Matsui  6 , Toshihide Takeuchi  2 , Kazumasa Saigoh  2 , Susumu Kusunoki  2 , Hiroshi Takashima  3 , Yoshitaka Nagai  2
Affiliations

CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy

Makito Hirano et al. Sci Rep. .

Abstract

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy.

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Conflict of interest statement

MH, MS, HT, and YN have received honoraria from Takeda. MH has received a research grant unrelated to this study from Takeda. HT and SK received honoraria from Japan Blood Product Organization. HT and SK have received honoraria from CSL Behring. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Repeat-primed PCR results for RFC1. Pathological repeats of AAGGG or ACAGG were expanded in patients with Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy with mild motor deficit (ISAN), MAG neuropathy, or sensory autonomic neuropathy with mild motor deficit (SAN).
Figure 2
Figure 2
Sural nerve biopsy findings in Patient 4. (A) A light microscopic image showing marked loss of myelinated fibers, without amyloidosis or vasculitis. (B) A lager image showing marked loss of both large and small myelinated fibers. (C) An electron microscopic image showing many collagen pockets (black arrow), reflecting unmyelinated fiber damage. (D) A Schwann cell had cytoplasmic dense materials (blue arrow). (E) Another Schwann cell had a cytoplasmic inclusion (yellow arrow). (F) The other Schwann cell had a cytoplasmic inclusion similar to the one shown in E (yellow arrow). (G) Membranous materials were seen between myelin sheaths (white arrow) or between a myelin sheath and an axon (white arrowhead). (H) Cells that constitute vessels had no abnormality without aggregation.
See this image and copyright information in PMC

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