Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort.

Ataxia Cerebellar Ataxia / genetics Cohort Studies Humans Replication Protein C / genetics Spinocerebellar Degenerations / genetics

CANVAS Gait disorders/ataxia Multiple system atrophy Peripheral neuropathy RFC1

Journal

Journal of neurology

ISSN: 1432-1459

Titre abrégé: J Neurol

Pays: Germany

ID NLM: 0423161

Informations de publication

Date de publication:
Sep 2021

Historique:

received: 16 11 2020

accepted: 25 02 2021

revised: 23 02 2021

pubmed: 6 3 2021

medline: 14 8 2021

entrez: 5 3 2021

Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1007/s00415-021-10499-5 PMID: 33666721

pubmed: 33666721

doi: 10.1007/s00415-021-10499-5

pii: 10.1007/s00415-021-10499-5

doi:

Substances chimiques

RFC1 protein, human 0

Replication Protein C EC 3.6.4.-

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

Pagination

3337-3343

Informations de copyright

Références

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