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Article Dans Une Revue Journal of Neurology Année : 2021

Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort

Solveig Montaut
  • Fonction : Auteur
Pauline Fahrer
  • Fonction : Auteur
Cécilia Marelli
  • Fonction : Auteur
Benoit Lhermitte
  • Fonction : Auteur
Marie Claire Vincent
  • Fonction : Auteur
Lucas Corti
  • Fonction : Auteur
Guillaume Taieb
  • Fonction : Auteur
Odile Gebus
  • Fonction : Auteur
Julien Tarabeux
  • Fonction : Auteur
Nicolas Dondaine
  • Fonction : Auteur
Matthieu Canuet
  • Fonction : Auteur
Marilyne Almeras
  • Fonction : Auteur
Mehdi Benkirane
  • Fonction : Auteur
Lise Larrieu
  • Fonction : Auteur
Aleksandra Nadaj-Pakleza
  • Fonction : Auteur
Cécile Cauquil
  • Fonction : Auteur
Béatrice Lannes
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-03709403 , version 1 (29-06-2022)

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Citer

Solveig Montaut, Nadege Diedhiou, Pauline Fahrer, Cécilia Marelli, Benoit Lhermitte, et al.. Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort. Journal of Neurology, 2021, 268 (9), pp.3337-3343. ⟨10.1007/s00415-021-10499-5⟩. ⟨hal-03709403⟩
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