Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort
© 2021. Springer-Verlag GmbH, DE part of Springer Nature..
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: 01. Sept., Seite 3337-3343 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Montaut, Solveig [VerfasserIn] |
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| Links: |
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| Themen: |
CANVAS |
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| Anmerkungen: |
Date Completed 13.08.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00415-021-10499-5 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322240514 |
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| 245 | 1 | 0 | |a Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 13.08.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. Springer-Verlag GmbH, DE part of Springer Nature. | ||
| 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) | ||
| 520 | |a METHODS: 163 patients were recruited in 3 French tertiary centers: 100 ILOA, 21 IEOA, and 42 patients with possible or probable MSA-C | ||
| 520 | |a 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 | ||
| 520 | |a 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 Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a CANVAS | |
| 650 | 4 | |a Gait disorders/ataxia | |
| 650 | 4 | |a Multiple system atrophy | |
| 650 | 4 | |a Peripheral neuropathy | |
| 650 | 4 | |a RFC1 | |
| 650 | 7 | |a RFC1 protein, human |2 NLM | |
| 650 | 7 | |a Replication Protein C |2 NLM | |
| 650 | 7 | |a EC 3.6.4.- |2 NLM | |
| 700 | 1 | |a Diedhiou, Nadège |e verfasserin |4 aut | |
| 700 | 1 | |a Fahrer, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Marelli, Cécilia |e verfasserin |4 aut | |
| 700 | 1 | |a Lhermitte, Benoit |e verfasserin |4 aut | |
| 700 | 1 | |a Robelin, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Vincent, Marie Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Corti, Lucas |e verfasserin |4 aut | |
| 700 | 1 | |a Taieb, Guillaume |e verfasserin |4 aut | |
| 700 | 1 | |a Gebus, Odile |e verfasserin |4 aut | |
| 700 | 1 | |a Rudolf, Gabrielle |e verfasserin |4 aut | |
| 700 | 1 | |a Tarabeux, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Dondaine, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Canuet, Matthieu |e verfasserin |4 aut | |
| 700 | 1 | |a Almeras, Marilyne |e verfasserin |4 aut | |
| 700 | 1 | |a Benkirane, Mehdi |e verfasserin |4 aut | |
| 700 | 1 | |a Larrieu, Lise |e verfasserin |4 aut | |
| 700 | 1 | |a Chanson, Jean-Baptiste |e verfasserin |4 aut | |
| 700 | 1 | |a Nadaj-Pakleza, Aleksandra |e verfasserin |4 aut | |
| 700 | 1 | |a Echaniz-Laguna, Andoni |e verfasserin |4 aut | |
| 700 | 1 | |a Cauquil, Cécile |e verfasserin |4 aut | |
| 700 | 1 | |a Lannes, Béatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Chelly, Jamel |e verfasserin |4 aut | |
| 700 | 1 | |a Anheim, Mathieu |e verfasserin |4 aut | |
| 700 | 1 | |a Puccio, Hélène |e verfasserin |4 aut | |
| 700 | 1 | |a Tranchant, Christine |e verfasserin |4 aut | |
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