Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:268 |
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| Enthalten in: |
Journal of neurology - 268(2021), 9 vom: 05. März, Seite 3337-3343 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Montaut, Solveig [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
CANVAS |
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| RVK: |
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| Anmerkungen: |
© Springer-Verlag GmbH, DE part of Springer Nature 2021 |
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| doi: |
10.1007/s00415-021-10499-5 |
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| PPN (Katalog-ID): |
OLC2127161424 |
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| 245 | 1 | 0 | |a Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort |
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| 520 | |a 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. | ||
| 650 | 4 | |a Gait disorders/ataxia | |
| 650 | 4 | |a Multiple system atrophy | |
| 650 | 4 | |a Peripheral neuropathy | |
| 650 | 4 | |a CANVAS | |
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| 700 | 1 | |a Fahrer, Pauline |4 aut | |
| 700 | 1 | |a Marelli, Cécilia |4 aut | |
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