Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort.
J Neurol
; 268(9): 3337-3343, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-33666721
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Degenerações Espinocerebelares
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Ataxia Cerebelar
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Proteína de Replicação C
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article