Journal of neurology · 2021
Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Montaut Solveig, Diedhiou Nadège, Fahrer Pauline, Marelli Cécilia, Lhermitte Benoit, Robelin Laura, Vincent Marie Claire, Corti Lucas, Taieb Guillaume, Gebus Odile, Rudolf Gabrielle, Tarabeux Julien, Dondaine Nicolas, Canuet Matthieu, Almeras Marilyne, Benkirane Mehdi, Larrieu Lise, Chanson Jean-Baptiste, Nadaj-Pakleza Aleksandra, Echaniz-Laguna Andoni, Cauquil Cécile, Lannes Béatrice, Chelly Jamel, Anheim Mathieu, Puccio Hélène, Tranchant Christine
Аннотация
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.
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.