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Multicenter Study
. 2021 Sep;268(9):3337-3343.
doi: 10.1007/s00415-021-10499-5. Epub 2021 Mar 5.

Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort

Solveig Montaut #  1 , Nadège Diedhiou #  2   3 , Pauline Fahrer  4 , Cécilia Marelli  5   6 , Benoit Lhermitte  7 , Laura Robelin  8   9 , Marie Claire Vincent  4 , Lucas Corti  10 , Guillaume Taieb  10 , Odile Gebus  4 , Gabrielle Rudolf  4   11 , Julien Tarabeux  12 , Nicolas Dondaine  12 , Matthieu Canuet  13 , Marilyne Almeras  14 , Mehdi Benkirane  15   16 , Lise Larrieu  15   16 , Jean-Baptiste Chanson  17 , Aleksandra Nadaj-Pakleza  17 , Andoni Echaniz-Laguna  18   19 , Cécile Cauquil  18 , Béatrice Lannes  8 , Jamel Chelly  11   12   20 , Mathieu Anheim  4   2   20 , Hélène Puccio  2   3 , Christine Tranchant  4   2   20
Affiliations
Multicenter Study

Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort

Solveig Montaut et al. J Neurol. 2021 Sep.

Abstract

Objective: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited multisystem ataxia compromising cerebellar, vestibular, and sensory nerves, which has been associated to a pathogenic AAGGG(n) biallelic expansion repeat in the RFC1 gene. Our objective was to assess its prevalence in a French cohort of patients with idiopathic sporadic late-onset ataxia (ILOA), idiopathic early-onset ataxia (IEOA), or Multiple System Atrophy of Cerebellar type (MSA-C).

Methods: 163 patients were recruited in 3 French tertiary centers: 100 ILOA, 21 IEOA, and 42 patients with possible or probable MSA-C.

Results: A pathogenic biallelic RFC1 AAGGG(n) repeat expansion was found in 15 patients: 15/100 in the ILOA group, but none in the IEOA and MSA-C subgroups. 14/15 patients had a CANVAS phenotype. Only 1/15 had isolated cerebellar ataxia, but also shorter biallelic expansions. Two RFC1 AAGGG(n) alleles were found in 78% of patients with a CANVAS phenotype. In one post-mortem case, the pathophysiological involvement of cerebellum and medullar posterior columns was found.

Conclusion: Our study confirms the genetic heterogeneity of the CANVAS and that RFC1 repeat expansions should be searched for preferentially in case of unexplained ILOA associated with a sensory neuronopathy, but not particularly in patients classified as MSA-C.

Keywords: CANVAS; Gait disorders/ataxia; Multiple system atrophy; Peripheral neuropathy; RFC1.

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